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  • 1.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mattsson, Christer
    Eriksson, Örjan
    Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock2000In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, E-ISSN 1744-7658, Vol. 9, no 5, p. 1129-1137Article in journal (Refereed)
    Abstract [en]

    Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.

  • 2.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Mutschler, Diana K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Propofol (Diprivan-EDTA) counteracts oxidative injury and deterioration of the arterial oxygen tension during experimental septic shock2001In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 50, no 3, p. 341-348Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Human septic shock can be replicated in the endotoxaemic pig. Endotoxaemia causes a multitude of events, including reduced PaO(2) and increased lipid peroxidation. This study was designed to evaluate the possible effects of a commonly used anaesthetic drug with known antioxidant properties (propofol) during porcine endotoxaemia.

    METHODS: Ten pigs were anaesthetised and given a 6 h E. coli endotoxin infusion. The animals received, randomly, a supplementary continuous infusion of propofol emulsion (containing 0.005% EDTA) or the corresponding volume of vehicle (controls). Pathophysiologic responses were determined. Non-enzymatic (by measuring plasma 8-iso-PGF(2 alpha) and enzymatic (by measuring plasma 15-keto-dihydro-PGF(2 alpha)) lipid peroxidations were evaluated. Plasma levels of the endogenous antioxidants alpha- and gamma-tocopherols, were also analysed.

    RESULTS: Endotoxaemia increased plasma levels of 8-iso-PGF(2 alpha) (1st-4th h) and 15-keto-dihydro-PGF(2 alpha) (1st-4th h) significantly more in controls than in the propofol+endotoxin group. PaO(2) was significantly less affected by endotoxin in the propofol treated animals (2nd-4th h). Mean arterial pressure (4th-6th h) and systemic vascular resistance (6th h) were reduced significantly more by endotoxin among the propofol-treated animals. Vitamin E (alpha-tocopherol) increased in all animals, significantly more in the propofol+endotoxin group (1/2-6th h) than in the control group.

    CONCLUSIONS: Propofol reduced endotoxin-induced free radical mediated and cyclooxygenase catalysed lipid peroxidation significantly. The implication is that propofol counteracts endotoxin-induced deterioration of PaO(2).

  • 3.
    Carlsson, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock: a model of endotoxin elimination2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 3, p. 1031-e4Article in journal (Refereed)
    Abstract [en]

    Objective:

    To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.

    Design:

    Prospective parallel-grouped placebo-controlled randomized interventional experimental study.

    Setting:

    University research unit.

    Subjects:

    Healthy pigs.

    Interventions:

    The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.

    Measurements and Main Results:

    During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.

    Conclusions:

    Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.

  • 4.
    Eriksson, Mats
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Should high mobility group box-1 protein (HMGB1) be measured in patients with severe sepsis and septic shock? If so, when, where, and how?2005In: Crit Care Med, ISSN 0090-3493, Vol. 33, no 3, p. 682-3Article in journal (Other scientific)
  • 5.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Christensen, K
    Lindahl, TL
    Larsson, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pharmaceutical thrombosis prevention in cardiovascular disease.2002In: Expert Opin Investig Drugs, Vol. 11, p. 553-Article in journal (Refereed)
  • 6.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Role of platelet microparticles in septic shock. International union of angiology congress 2002, New York, April 7 - 11,2002Article, book review (Other academic)
  • 7.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The effect of hemorrhagic shock and intraosseous adrenaline injection on the delivery of a subsequently administered drug - an experimental study2019In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, E-ISSN 1757-7241, Vol. 27, article id 29Article in journal (Refereed)
    Abstract [en]

    Background: Intraosseous (IO) access is a recommended method when venous access cannot be rapidly established in an emergency. Experimental data suggest that major hemorrhage and catecholamine administration both reduce bone marrow blood flow. We studied the uptake of gentamicin as a tracer substance administered IO following adrenaline administration in hemorrhagic shock and in cardiac arrest.

    Methods: Twenty anesthetized pigs underwent hemorrhage corresponding to 50% of the blood volume. They then received injections of either; adrenaline IO (n=5), saline IO n=5), adrenaline IO during cardiac arrest and cardiopulmonary resuscitation (CPR, n=5), or intravenous adrenaline. The injections were followed by an injection of gentamicin by the same route. Doses and volumes were equivalent among the groups. In all animals, mixed venous antibiotic concentrations were analyzed at 5, 15 and 30min after administration.

    Results: Mean (SD) plasma gentamicin concentrations (mg x L-1) at 5min were 26.4 (2.3) in the group with previous IO adrenaline administration, 26.6 (4.5) in the IO saline group, 31. 2 (12) in the IO adrenaline + CPR group and 23 (4.5) in the IV group. Concentrations in the CPR group were significantly higher than the others.

    Conclusions: No impairment of drug uptake with IO administration after recent IO adrenaline exposure was demonstrable in this shock model.

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  • 8.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bestämning av kalprotektin av värde vid diagnostik av svår infektion.2021In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 118, p. 370-371Article in journal (Refereed)
  • 9.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mutschler, Diana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Brännström, Charina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Palmberg, Kicki
    Porjebäck, Anita
    Johansson, Kerstin
    Lööf-Lang, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sjöberg, Marianne
    Utvärdering av Hemocue urin-albumin metod2002In: Klinisk kemi, ISSN 0282-440X, no 2Article in journal (Other academic)
  • 10.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nilsson, Bo
    Modig, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Acosta,
    Johansson,
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fallbeskrivning Hypotensiv reaktion orsakades av albumininfusion.2001In: Läkartidningen, Vol. 98, p. 438-Article in journal (Other academic)
  • 11.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Saldeen, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Mattsson, C
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of melagatran, an inhibitor of thrombin, on fibrin deposits,haemodynamics, and platelet count in endotoxaemic pigs.2000In: Acta Anaesthesiol. Scand., Vol. 44, p. 24-Article in journal (Refereed)
  • 12.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    inst för medicinska vetenskaper.
    Troponin I can be Determined in Intraosseous Aspirates in a Porcine Shock Model2015In: Clinical Laboratory, ISSN 1433-6510, Vol. 61, no 7, p. 825-829Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Determination of troponin I may be important in the management of the critically ill patient. In medical emergencies, especially when vascular access is difficult to achieve, the use of intraosseous (10) needles is recommended. We aimed to perform a descriptive study, aiming to elucidate whether IO needles can be used to evaluate troponin I in a porcine model of human shock.

    METHODS: Eight pigs were anesthetized and challenged with a 6 hours continuous intravenous infusion of E. coli endotoxin. An IO needle (EZ-IO®) was inserted in the proximal tibia of each pig. Circulatory variables were monitored and troponin I was sampled from arterial and venous blood and also from bone marrow aspirates.

    RESULTS: Circulatory deterioration developed in all endotoxemic animals, which was reflected by a profound deterioration of left ventricular stroke work index. Troponin I levels were nearly identical in both arterial, venous, and IO samples during the first hour of endotoxemia. At 1 hour, all mean troponin I levels had more than doubled as compared to baseline. The troponin I levels continued to increase over time and were markedly elevated versus baseline levels during the 2nd and 6th hours, regardless of sampling site. At 3 hours, IO troponin I reached a plateau, whereas troponin I in both arterial and venous blood continued to increase.

    CONCLUSIONS: This investigation has shown that troponin I can be analyzed in bone marrow aspirates in a shock model. This may be useful in medical emergencies, where cardiac damage is suspected to be involved. The levels of IO troponin I increased during the first 3 hours of shock, after which it remained at a high level. During this initial period there was, in parallel, a progressive circulatory deterioration.

  • 13.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Dörenberg, R
    Intracardiac ECG for confirmation of correct positioning of central venous catheters is safe and cost-effective2013Conference paper (Refereed)
  • 14.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    10th Anniversary of Biomedicines—Biomarkers in Pain2023Book (Refereed)
    Abstract [en]

    Pain biomarkers are biological indicators or measurable characteristics that can provide information about the presence, severity, or underlying mechanisms of pain. They are valuable for several reasons: Diagnosis and differential diagnosis: Biomarkers can help in the diagnosis of various pain conditions and differentiate between different types of pain, such as neuropathic, inflammatory, or nociceptive pain. This can lead to more accurate and timely diagnoses, which in turn can improve patient care. Monitoring treatment efficacy: Pain biomarkers can be used to track how well treatments are working for individuals suffering from chronic pain conditions. This allows healthcare providers to make informed decisions about adjusting treatment plans, optimizing pain management, and avoiding unnecessary or ineffective interventions. Drug development and testing: Biomarkers play a crucial role in the development of new pain medications and therapies. They can help researchers identify potential drug targets, screen compounds for their pain-relieving properties, and assess the safety and efficacy of experimental treatments in clinical trials. Personalized medicine: Pain biomarkers may, in a future, contribute to treatments, tailored to an individual's unique genetic and biological disposition. Reducing opioid misuse: By using biomarkers to assess pain and treatment responses, healthcare providers can make more informed decisions about opioid prescriptions, potentially reducing the overuse and abuse of these medications.

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  • 15.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Emergency intraosseous access: novel diagnostic and therapeutic possibilities and limitations2016In: ICU Management & Practice, Vol. 16, no 4, p. 230-232Article in journal (Refereed)
    Abstract [en]

    The intraosseous needle is an essential tool in emergency settings when initial vascular access is difficult to achieve. This paper focuses on possible biochemical analyses on blood from emergency intraosseous needles, suggesting principles of use as well as pointing out advantages and shortcomings.

  • 16.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nelson, D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Increased platelet microvesicle formation is associated with mortality ina porcine model of endotoxemia1998In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 42, no 5, p. 551-557Article in journal (Refereed)
    Abstract [en]

    Background:

    Gram-negative sepsis in humans and endotoxemia in pigs induce the formation of platelet microvesicles. These microvesicles are active in homeostasis and may thus contribute to the outcome in patients with activated coagulation and fibrinolysis. We decided to prospectively evaluate the effects of endotoxemia on microvesicle formation and some common physiologic variables against survival in a porcine model.

    Methods:

    Nineteen included pigs were anesthetized, monitored and subjected to an infusion of E. coli endotoxin. Microvesicle formation was determined by flow cytometry.

    Results:

    The formation of microvesicles was significantly increased in the 6 pigs that died during endotoxin exposure. This increased formation became significant from the 3rd hour of endotoxemia. Microvesicle formation did not increase in surviving endotoxemic pigs. Cardiac index, mean arterial blood pressure, base excess and systemic vascular resistance index were distinctly reduced in the animals that died as compared to those surviving the endotoxemic period.

    Conclusion:

    The increased formation of platelet microvesicles seems to be associated with poor prognosis in porcine endotoxemia. Since microvesicles are active in coagulation, they may contribute to the derangement of the coagulation system caused by endotoxemia. Different degrees of microvesicle formation may reflect inter-individual responses to a given challenge.

  • 17.
    Eriksson, Mats
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, Bo
    Department of Oncology, Radiology and Clinical Immunology. Klinisk immunologi.
    Modig, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Acosta, Rafael
    Johansson, Bo
    Larsson, Anders
    Department of Medical Sciences.
    [A case report. Hypotensive reaction caused by albumin infusion]2001In: LäkartidningenArticle in journal (Other scientific)
  • 18.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Evaluation of intraosseous sampling for measurements of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate dehydrogenase.2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 8, p. 597-600Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Intraosseous (IO) access can be established faster than a venous or arterial access when there is an urgent need for rapid initiation of treatment. The access can also be used to draw marrow samples. The aim of the present study was to evaluate the potential use of IO samples for enzyme determinations using a porcine model.

    MATERIALS AND METHODS: Bilateral tibial intraosseous cannulae and an arterial catheter were used for blood sampling from five healthy anesthetized pigs. Samples were collected at baseline and thereafter hourly for 6 h and analyzed for alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate dehydrogenase.

    RESULTS: Creatinine kinase, lactate dehydrogenase and alkaline phosphatase levels decreased over time. The differences between IO and arterial sampling were limited for all studied markers.

    CONCLUSION: The correlation between marrow and blood analysis for liver function tests and CK is sufficiently accurate in an emergency situation.

  • 19.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Intraosseös provtagning kan vara värdefull i akuta lägen2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 9, p. 395-396Article in journal (Refereed)
    Abstract [sv]

    En intraosseös infart kan ha stor klinisk betydelse i den akuta situationen då det är svårt att få kärlaccess.Provtagning via intraosseösanålar har ifrågasatts med tanke på risken att aspirera benmärgs-partiklar.Vi rekommenderar, så långt det är möjligt, patientnära metoder för intraosseösa prov. Detta gäl-ler särskilt då helblod (exempel-vis blodgaser) ska analyseras.Vid centrifugering av intraosse-öst aspirat kommer eventuella benmärgspartiklar att hamna i pelleten. Supernatanten motsva-rar närmast plasma. Vi har på så sätt analyserat kreatinin, morfin och troponin i intraosseösa prov.Leukocyter och trombocyter,vilka bildas i benmärgen, kan ge falskt förhöjda värden vid analys av intraosseösa prov. Risken för hemolys bör övervägas.

  • 20.
    Goscinski, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tano, Eva
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Anti-inflammatory effects of the antibiotics ceftazidime and tobramycin in porcine endotoxin shock: are they really anti-inflammatory? Authors' response.2004In: Crit Care, ISSN 1466-609X, Vol. 8, no 2, p. 141-Article in journal (Other academic)
  • 21.
    Goscinski, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Infektion.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Infektion.
    Endotoxin neutralisation and anti-inflammatory effects by tobramycin and ceftazidime in porcine endotoxic shock2003In: Cricical Care, Vol. Suppl2, p. 125-Article in journal (Refereed)
  • 22. Goscinski, Gunilla
    et al.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tano, Eva
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock2004In: Critical care, ISSN 1364-8535, Vol. 8, no 1, p. 35-41Article in journal (Refereed)
  • 23.
    Havelka, Aleksandra
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institute, 171 76 Stockholm, Sweden..
    Larsson, Anders O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Mårtensson, Johan
    Department of Physiology and Pharmacology, Section of Anaesthesiology and Intensive Care Medicine, Karolinska Institute, 171 77 Stockholm, Sweden..
    Bell, Max
    Department of Physiology and Pharmacology, Section of Anaesthesiology and Intensive Care Medicine, Karolinska Institute, 171 77 Stockholm, Sweden..
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Department of Epidemiology, McGill University, Montréal, QC H3A 0G4, Canada; Lady Davis Institute of Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. NOVA Medical School, New University of Lisbon, 1099-085 Lisbon, Portugal.
    Analysis of Calprotectin as an Early Marker of Infections Is Economically Advantageous in Intensive Care-Treated Patients2023In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 8, article id 2156Article in journal (Refereed)
    Abstract [en]

    Calprotectin is released from neutrophil granulocytes upon activation. Several studies have indicated that plasma calprotectin is an early determinant of bacterial infections, which may serve as a diagnostic tool facilitating decision making on antibiotic treatment. The study objective was to explore the health and economic implications of calprotectin as a predictive tool to initiate antimicrobial therapy in a cohort of critically ill patients. Thus, data obtained from a previously published study on calprotectin as a hypothetical early biomarker of bacterial infections in critically ill patients were evaluated regarding the potential cost-effective impact of early analysis of calprotectin on an earlier start of antibiotic treatment. Under the assumption that calprotectin is used predictively and comparators (white blood cells, procalcitonin, and C-reactive protein) are used diagnostically, a cost-effective impact of EUR 11,000-12,000 per patient would be obtained. If calprotectin would be used predictively and comparators would be used predictively for 50% of patients, it is hypothesized that cost-effectiveness would be between EUR 6000 and 7000 per patient, based on reduced stay in the ICU and general ward, respectively. Furthermore, predictive use of calprotectin seems to reduce both mortality and the length of hospital stay. This health economic analysis on the predictive use of plasma calprotectin, which facilitates clinical decision making in cases of suspected sepsis, indicates that such determination has a cost-saving and life-saving impact on the healthcare system.

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  • 24.
    Johansson, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wahlqvist, Inger
    von zur Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Effects of blockade of alpha- and beta-adrenoceptors and neuropeptide Y(1) receptors, as well as brachial plexus blockade, on endothelium-dependent vasodilation in the human forearm2002In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 29, no 7, p. 603-607Article in journal (Refereed)
    Abstract [en]

    1. The aim of the present study was to investigate the effects of alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol), neuropeptide Y(1) receptor blockade and neurogenic blockade (brachial plexus) on endothelium-dependent vasodilation (EDV) in the human forearm. 2. Forty-four young healthy volunteers underwent forearm blood flow (FBF) measurements, using venous occlusion plethysmography, during local intra-arterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation (EIDV)). These measurements were undertaken at baseline and were repeated with either concomitant local intra-arterial infusion of phentolamine (n = 8), propranolol (n = 7) or saline (n = 6) in the forearm, neuropeptide Y(1) receptor blockade (n = 12) given i.v. or during axillary plexus blockade (n = 11). 3. Both alpha-adrenoceptor blockade and neurogenic blockade induced an upward shift in the dose-response curve for both EDV and EIDV. beta-Adrenoceptor blockade did not change resting FBF or EIDV, but induced a significant decrease in EDV (P = 0.015). Neuropeptide Y(1) receptor blocker induced no significant changes in resting FBF, EDV and EIDV and neither did saline. No changes in blood pressure or heart rate were induced by any of the blockades. 4. Whereas beta-adrenoceptor blockade impaired EDV, alpha-adrenoceptor blockade and neurogenic blockade caused a general vasodilation that was not endothelium dependent. Neuropeptide Y does not seem to influence blood flow in the resting forearm.

  • 25.
    Kiiski, Ritva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hänni, Arvo
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Carlstedt, Fredrik
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    An inhibitor of angiotensin converting enzyme (enalapril) augments endotoxin-induced hypotension in the pig1999In: Upsala Journal of Medical Sciences, ISSN 0300-9734, Vol. 104, no 2, p. 163-176Article in journal (Refereed)
    Abstract [en]

    Septic shock causes an extensive inflammatory reaction including increased capillary leakage and a decrease in systemic blood pressure. Human septic shock can be replicated in the endotoxaemic pig. Angiotensin converting enzyme (ACE) is involved in the degradation of bradykinin, an inflammatory mediator, and in the regulation of blood pressure. Inhibition of ACE is a common approach to reduce hypertension as well as left ventricular insufficiency. Fifteen anaesthetised pigs received a continuous 3 h endotoxin infusion. The animals were randomly given an inhibitor of ACE (enalpril) [at a dose (0.5 mg x kg-1) that did not per se reduce mean arterial blood pressure (MAP); (n = 7)], or the corresponding volume of saline (n = 8). Another seven pigs were randomised for treatment with enalapril (0.5 mg x kg-1) + saline (n = 3). Four pigs were randomised to serve as untreated controls (saline + saline). Basic physiologic variables were registered. Endotoxaemia progressively reduced MAP. This decrease was significantly augmented by enalapril. Hypovolemia caused by increased permeability or salt/water excretion did not seem to explain this effect as neither blood haemoglobin nor plasma sodium differed between the two groups of endotoxaemic pigs. Inhibitors of ACE are known to potentiate the cardio-depressant effect of bradykinin. This may explain the reduction in MAP by enalapril during porcine endotoxaemia.

  • 26.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Campbell, Andrew
    NABAS AS, Ås, Norway..
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. NOVA Medical School, New University of Lisbon, Lisboa, Portugal.
    Chicken antibodies are highly suitable for particle enhanced turbidimetric assays2022In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 1016781Article in journal (Refereed)
    Abstract [en]

    Antibody-based assays are commonly used in clinical laboratories for analyzing plasma, serum and other samples for particular protein markers. Although such assays have been traditionally based on antibodies raised in mammals (e.g., mice, rabbits, goats), there are several advantages of using avian antibodies (IgY) raised in chickens, including production volumes, costs, and ethical/animal welfare considerations. A further disadvantage of using mammalian IgG in such assays is the potential for agglutination when exposed to rheumatoid factor (RF) in serum. However, when used in the free form the immune complexes formed with avian antibodies have been reported to have less ability than those formed with mammalian antibodies to cause the light scatter which are used for instrument measurement. In addition, when the amount of antigen exceeds the maximum precipitating point in relation to the amount of antibody, there is a rapid decline in the absorbance values of the immune complexes (antigen excess) when IgY is used. However, when avian antibodies are conjugated to a substrate and used in particle enhanced turbidimetric assays (PETIA), these problems are avoided. Here we investigated three clinical assays using chicken antibodies, one using free (unbound) IgY and two with IgY-based PETIA. The IgY PETIA demonstrated a strong scatter response, even at high antigen concentrations in contrast to the steep decline seen with free IgY antibodies. IgY PETIA reagents can provide test results with low coefficient of variation (<1% for duplicate samples). We also investigated the effect of RF on agglutination of mammalian antibodies (IgG from mouse, rabbit, sheep, and human) and chicken antibodies. Whereas agglutination was observed with all the mammalian antibodies in the presence of RF, this was not observed at all with chicken IgY. Our results support the growing body of evidence that chicken egg yolks can thus be a valuable source of antibodies for use in PETIA in clinical laboratories.

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  • 27.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. NOVA Medical School, New University of Lisbon, Lisbon, Portugal.
    Validation of a Novel Point-of-Care Testing Device Designed for Assessment of NT-pro BNP2023In: Journal of Family Medicine and Primary Care Open access, ISSN 2688-7460, Vol. 7, no 2Article in journal (Refereed)
    Abstract [en]

    Aim: Our main objective was to compare Point-Of-Care Technology (POCT) to central laboratory immunochemistry testing, to assess N-terminal pro B-type Natriuretic Peptide (NT-proBNP) in ambulatory patients. A second objective was to use POCT to analyze NT-proBNP in a cohort of healthy blood donors to define reference values. Methods: Blood samples were obtained from 102 outpatients and 133 blood donors, respectively. Samples analyzed using a point-of-care instrument [NT-proBNPLumiraDx (LumiraDx, Solna, Sweden)] were compared to a commercial electrochemiluminescence immunoassay method [(NTproBNPRoche) on the Cobas Pro analyzer (Roche Diagnostics, Mannheim, Germany)]. The study was ethically approved (01–367) and complied with the Declaration of Helsinki. Values are given as Median and Interquartile Range (IQR). Results: There was a distinct correlation between the two assays for assessing the circulating levels of NT-proBNP in outpatients (R² = 0.9546). NT-proBNPLumiraDx ranged between 50–3966 ng/L [Median: 276 (IQR: 679)] whereas NT-proBNPRoche ranged between 50–3820 ng/L; (Median: 268 (IQR: 628)]. NT-proBNPLumiraDx was 3% higher than NT-proBNPRoche (p<0.05). NT-proBNPLumiraDx levels were not affected by age in our cohort of blood donors. Conclusion: In cases where short turnaround-times for assessment of NT-proBNP are desirable, the LumiraDx instrument can safely be used as an analytical option.

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  • 28.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Department of Epidemiology, McGill University, Montréal, QC H3A 0G4, Canada.; Lady Davis Institute of Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada..
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nyman, Ulf
    Department of Translational Medicine, Division of Medical Radiology, Lund University, 221 85 Malmö, Sweden..
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. NOVA Medical School, New University of Lisbon, 1099-085 Lisbon, Portugal..
    Differential Bias for Creatinine- and Cystatin C- Derived Estimated Glomerular Filtration Rate in Critical COVID-19.2022In: Biomedicines, E-ISSN 2227-9059, Vol. 10, no 11, article id 2708Article in journal (Refereed)
    Abstract [en]

    COVID-19 is a systemic disease, frequently affecting kidney function. Dexamethasone is standard treatment in severe COVID-19 cases, and is considered to increase plasma levels of cystatin C. However, this has not been studied in COVID-19. Glomerular filtration rate (GFR) is a clinically important indicator of renal function, but often estimated using equations (eGFR) based on filtered metabolites. This study focuses on sources of bias for eGFRs (mL/min) using a creatinine-based equation (eGFRLMR) and a cystatin C-based equation (eGFRCAPA) in intensive-care-treated patients with COVID-19. This study was performed on 351 patients aged 18 years old or above with severe COVID-19 infections, admitted to the intensive care unit (ICU) in Uppsala University Hospital, a tertiary care hospital in Uppsala, Sweden, between 14 March 2020 and 10 March 2021. Dexamethasone treatment (6 mg for up to 10 days) was introduced 22 June 2020 (n = 232). Values are presented as medians (IQR). eGFRCAPA in dexamethasone-treated patients was 69 (37), and 74 (46) in patients not given dexamethasone (p = 0.01). eGFRLMR was not affected by dexamethasone. eGFRLMR in females was 94 (20), and 75 (38) in males (p = 0.00001). Age and maximal CRP correlated negatively to eGFRCAPA and eGFRLMR, whereas both eGFR equations correlated positively to BMI. In ICU patients with COVID-19, dexamethasone treatment was associated with reduced eGFRCAPA. This finding may be explained by corticosteroid-induced increases in plasma cystatin C. This observation is important from a clinical perspective since adequate interpretation of laboratory results is crucial.

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  • 29.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Plasma Leptin Is Increased in Intensive Care Patients with COVID-19—An Investigation Performed in the PronMed-Cohort2022In: Biomedicines, E-ISSN 2227-9059, Vol. 10, no 1, p. 4-4Article in journal (Refereed)
    Abstract [en]

    Abstract: COVID-19 has shaken the world and intensive care units (ICU) have been challenged by numerous patients suffering from a previously unknown disease. Leptin is a polypeptide pleiotropic hormone, mainly expressed by adipocytes. It acts as a proinflammatory cytokine and is associated with several conditions, known to increase the risk of severe COVID-19. Very little is known about leptin in severe viral disorders. Plasma leptin was analyzed in 222 out of 229 patients with severe COVID-19 on admission to an ICU at Uppsala University Hospital, a tertiary care hospital in Sweden, and compared to plasma leptin in 25 healthy blood donors. COVID-19 was confirmed by positive PCR. Leptin levels were significantly higher in patients with COVID-19 (18.3 ng x mL-1; IQR = 30.4), than in healthy controls (7.8 ng x mL-1; IQR = 6.4). Women had significantly higher leptin values (22.9 ng x mL-1; IQR = 29.8) than men (17.5 ng x mL-1; IQR = 29.9). Mortality at 30 days was 23%, but was not associated with increased leptin levels. Neither median duration of COVID-19 before admission to ICU (10 days; IQR = 4) or median length of ICU stay (8 days; IQR = 11) correlated with the plasma leptin levels. Leptin levels in COVID-19 were higher in females than in males. Both treatment (e.g. use of corticosteroids) and prophylaxis (vaccines) have been improved since the start of the COVID-19 pandemic, which may contribute to some difficulties in deciphering relations between COVID-19 and leptin.

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  • 30.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Klinisk kemi.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Infektion.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Klinisk kemi.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Slight Increase of Serum S-100B During Porcine Endotoxemic Shock May Indicate Blood-Brain Barrier Damage.2005In: Anesth Analg, ISSN 0003-2999, Vol. 101, no 5, p. 1465-9Article in journal (Refereed)
    Abstract [en]

    Septic shock is a condition that affects many organs, but little is known about the effects on the central nervous system. S-100B, an acidic low molecular weight protein, has attracted considerable interest as a marker for brain damage and disintegration of the blood-brain barrier. It is released into the cerebrospinal fluid and blood from brain tissue after brain damage. We studied S-100B in a porcine model of endotoxemic shock that resembles human Gram-negative septic shock. Ten piglets received IV endotoxin, and plasma samples were collected before the endotoxin infusion and each hour (1-6 h) during the endotoxin infusion. S-100B was measured by sandwich enzyme-linked immunosorbent assay. Low levels of plasma S-100B were detected, but there was a significant increase in S-100B during Hours 1-5 in comparison with the 0 values. We determined that endotoxemia causes a very small but significant increase in the levels of the widely used brain damage marker serum S-100B. However, it cannot be excluded that the increase in S-100B could be caused by release from organs other than the brain.

  • 31.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Fallbeskrivning. Trombocytopeni orsakad av legionärsjuka.2001In: Klinisk Kjemi i Norden, Vol. 3, p. 8-Article in journal (Other academic)
  • 32.
    Larsson, Anders O.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bäckryd, Emmanuel
    Pain and Rehabilitation Center, and Department of Health, Medicine and Caring Sciences, Linköping University, 581 83 Linköping, Sweden..
    Eriksson, Mats B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. NOVA Medical School, New University of Lisbon, 1099-085 Lisbon, Portugal.
    Biomarkers in Pain2023In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 9, article id 2554Article in journal (Other academic)
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  • 33.
    Larsson, Anders O.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Department of Epidemiology, McGill University, Montréal, QC H3A 0G4, Canada; Lady Davis Institute of Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. NOVA Medical School, New University of Lisbon, 1099-085 Lisbon, Portugal.
    Shrunken Pore Syndrome Is Frequently Occurring in Severe COVID-192022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 24, article id 15687Article in journal (Refereed)
    Abstract [en]

    A selective decrease in the renal filtration of larger molecules is attributed to the shrinkage of glomerular pores, a condition termed Shrunken Pore Syndrome (SPS). SPS is associated with poor long-term prognosis. We studied SPS as a risk marker in a cohort of patients with COVID-19 treated in an intensive care unit. SPS was defined as a ratio &lt; 0.7 when the estimated glomerular filtration rate (eGFR), determined by cystatin C, calculated by the Cystatin C Caucasian-Asian-Pediatric-Adult equation (CAPA), was divided by the eGFR determined by creatinine, calculated by the revised Lund-Malmö creatinine equation (LMR). Clinical data were prospectively collected. In total, SPS was present in 86 (24%) of 352 patients with COVID-19 on ICU admission. Patients with SPS had a higher BMI, Simplified Physiology Score (SAPS3), and had diabetes and/or hypertension more frequently than patients without SPS. Ninety-nine patients in the total cohort were women, 50 of whom had SPS. In dexamethasone-naïve patients, C-reactive protein (CRP ), TNF-alpha, and interleukin-6 did not differ between SPS and non-SPS patients. Demographic factors (gender, BMI) and illness severity (SAPS3) were independent predictors of SPS. Age and dexamethasone treatment did not affect the frequency of SPS after adjustments for age, sex, BMI, and acute severity. SPS is frequent in severely ill COVID-19 patients. Female gender was associated with a higher proportion of SPS. Demographic factors and illness severity were independent predictors of SPS.

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  • 34.
    Larsson, Anders O.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Department of Epidemiology, McGill University, Montréal, Quebec, Canada;Lady Davis Institute of Medical Research, Jewish General Hospital, Montréal, Quebec, Canada.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Nyman, Ulf
    Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden..
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. NOVA Medical School, New University of Lisbon, Lisboa, Portugal.
    Estimated glomerular filtration rates are higher when creatinine-based equations are compared with a cystatin C-based equation in coronavirus disease 20192023In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 67, no 2, p. 213-220Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Estimations of glomerular filtration rate (eGFR) are based on analyses of creatinine and cystatin C, respectively. Covid-19 patients in the intensive care unit (ICU) often have acute kidney injury and are at increased risk of drug induced kidney injury. The aim of this study was to compare creatinine-based eGFR equations to cystatin C-based eGFR in ICU patients with COVID-19.

    METHODS: After informed consent, we included 370 adult ICU patients with COVID-19. Creatinine and cystatin C were analyzed at admission to the ICU as part of the routine care. Creatinine-based eGFR (mL/min) was calculated using following equations, developed in chronological order; the Cockcroft-Gault (C-G), MDRD 1999, MDRD 2006, CKD-EPI and LMR equations, which were compared with eGFR calculated using the cystatin C-based CAPA equation.

    RESULTS: The median eGFR when determined by C-G was 99 mL/min and interquartile range (IQR: 67 mL/min). Corresponding estimations for MDRD1999 were 90 mL/min (IQR: 54); MDRD2006: 85 mL/min (IQR: 51); CKD-EPI: 91 mL/min (IQR: 47); and for LMR 83 mL/min (IQR: 41). eGFR calculated using cystatin C and the CAPA equation values was 70 mL/min (IQR: 38). All differences between creatinine based eGFR versus cystatin C based eGFR were significant (p<0.00001).

    CONCLUSIONS: Estimation of GFR based on various analyses of creatinine are higher when compared to a cystatin C-based equation. The C-G equation had the worst performance and should not be used in combination with modern creatinine analysis methods for determination of drug dosage in COVID-19 patients.

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  • 35.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of extensive bleeding in pigs on laboratory biomarkers2021In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 126, no 1, article id e6914Article in journal (Refereed)
    Abstract [en]

    Background: During hemorrhage and resuscitation, clinical and laboratory monitoring is useful to guide further management. However, acute changes in the biochemistry due to blood loss and subsequent crystalloid fluid resuscitation have not been fully studied.

    Materials and methods: Twelve anesthetized, juvenile pigs were used. Atraumatic exsanguination, corresponding to a total blood loss of 40%, was performed through a catheter and completed 2 h after initiation of the experiment. Arterial samples were analyzed by point-of-care testing and venous samples were analyzed. Oxygen delivery was calculated.

    Results: Shortly after 40% hemorrhage and concomitant fluid supplementation, there were significant reductions in arterial hemoglobin and hematocrit (approximately 25%, respectively). Oxygen delivery was less than half of the baseline value. Lactate in arterial blood was more than doubled after 40% exsanguination. On average, no other clinically significant changes in any of the analytes were observed, but interindividual dispersion was pronounced.

    Conclusions: Acute exsanguination was associated with decreased hemoglobin and hematocrit levels and increased lactate levels but limited effects on the other biomarkers that were studied. Increased levels of biomarkers in severely bleeding patients could indicate tissue damage and the source should be further investigated.

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  • 36.
    Larsson, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bondesson, Ulf
    National Veterinary Institute (SVA), Department of Chemistry, Environment and Feed Hygiene, Uppsala, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Intraosseous samples can be used for opioid measurements: An experimental study in the anaesthetized pig2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 2, p. 102-106Article in journal (Refereed)
    Abstract [en]

    Aim.

    The intraosseous route provides access to the systemic circulation in an emergency situation when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. The intraosseous access has also been used for collecting samples for laboratory testing. A question that may arise in an unconscious or severely exhausted patient is whether this condition is caused by an unknown drug. We aimed to evaluate whether intraosseous samples could be used to measure opioids and to study the accuracy and precision of such measurements.

    Methods.

    Five healthy, anaesthetized pigs were treated with a continuous morphine infusion as part of the anaesthesia procedure. Samples for morphine testing were collected hourly for 6 h from two tibial intraosseous cannulae and a central venous catheter.

    Results.

    The differences in morphine concentrations between the two tibial intraosseous cannulae were less than 10% in 32/33 times. The values were also relatively stable over time.

    Conclusion.

    Our findings suggest that intraosseous samples can be used for the analysis of opioids if an IV route is not available.

  • 37.
    Lind, Lars
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Mats
    Department of Surgical Sciences.
    Influence of nervous blockade on insulin-mediated glucose uptake in the human forearm.2003In: Metabolism, ISSN 0026-0495, Vol. 52, no 4, p. 413-7Article in journal (Refereed)
  • 38.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Carlsson, Markus
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Algotsson, Lars
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lukinius, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 10, p. 2782-2790Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury.

    DESIGN:

    Prospective, randomized, placebo-controlled experimental study.

    SETTING:

    University research unit.

    SUBJECTS:

    Twenty-four healthy pigs.

    INTERVENTIONS:

    The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline.

    MEASUREMENTS AND MAIN RESULTS:

    The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups.

    CONCLUSIONS:

    The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury.

  • 39.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Samar, Basu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Oxidative stress in animal models with special reference to esperimental porcine endotoxemia2011In: Studies on experimental models / [ed] Samar Basu & Lars Wiklund, Totowa, NJ: Springer Science+Business Media B.V., 2011, p. 497-510Chapter in book (Refereed)
  • 40.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Inflammatory, coagulatory and circulatory responses to logarithmic increases in the endotoxin dose in the anaesthetised pig2006In: Journal of Endotoxin Research, ISSN 0968-0519, E-ISSN 1743-2839, Vol. 12, no 2, p. 99-112Article in journal (Other academic)
    Abstract [en]

    Although porcine intravenous endotoxin shock models are widely employed in experimental sepsis, endotoxin dose-effect studies are scarce. Our primary aim was to establish the dose response to increasing endotoxin doses in inflammatory, coagulatory and haemodynamic effect variables, as well as to determine the optimal time point for assessment in a pig model. A secondary aim was to study pathophysiological covariations between the different responses. Twenty anaesthetised piglets received endotoxin intravenously in doses of 0.063 (n = 3), 0.25 (n = 3), 1.0 (n = 3), 4.0 (n = 3), 8 (n = 3) and 16 microg/kg/h (n = 2). In addition, non-endotoxin piglets constituted a control group (n = 3). Physiological variables were registered and blood samples analysed for TNF-alpha, IL-6, leukocyte, platelet and haemoglobin concentrations hourly for 6 h. Increases in the endotoxin dose induced significant log-log cytokine responses as well as log-linear leukocyte and platelet responses. Significant log-linear responses were observed for circulatory parameters, plasma leakage, hypoperfusion and pulmonary compliance. Significant covariations in the responses were noted. In conclusion, there were log-log or log-linear responses to endotoxin suggesting a greater effect of a given dose at lower pre-existing endotoxin concentrations and lower doses of < or = 1 microg/kg/h may be of advantage in experiments designed to study potential anti-endotoxin effects of experimental drugs or measures.

  • 41.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Effect of the Administration Rate on the Biological Responses To A Fixed Dose of Endotoxin in the Anesthetized Pig2008In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 29, no 2, p. 173-180Article in journal (Refereed)
    Abstract [en]

    There have been difficulties to demonstrate a relationship between endotoxin concentration and clinical response. One hypothesis for this difficulty might be that a fast increase in endotoxin concentration elicits a stronger biological response than a more gradual one of the same dose. The aim of the present study was to investigate the existence of such a response. Eighteen randomized pigs were given the same amount of endotoxin either with an initial infusion rate of 4 μg kg-1 h-1, which after 1 h was tapered to 0.5 μg kg-1 h-1, and after 2 h to 0.063 μg kg-1 h-1 (group I), or with a reverse escalating order with the lowest infusion rate given first (group II). After 3 h, the endotoxin infusion was stopped, and the pigs were observed for another 3 h. The responses in TNF-α, core temperature, leukocytes, platelets, MAP, left ventricular stroke work index, mixed venous saturation, base excess, pH, and pulmonary compliance were greater in group I than in group II, whereas the IL-6 response did not differ between groups. The biological responses of inflammation, hypotension, hypoperfusion, and organ dysfunction are increased if the organism is exposed to a fixed amount of endotoxin more quickly.

    Abbreviations - BE-Base excess; CI-Cardiac index; DO2-Oxygen delivery; Fio2-fraction of oxygen; Hb-Hemoglobin; LVSWI-Left ventricular stroke work index; MPAP-Mean pulmonary arterial pressure; Paco2-Arterial partial pressure of carbon dioxide; Pao2-Arterial partial pressure of oxygen; pH-Potentia Hydrogenii; SEM-Standard error of the mean; Svo2-Venous oxygen saturation

  • 42.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Early endotoxin-mediated haemostatic and inflammatory responses in the clopidogrel-treated pig2005In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 16, no 7, p. 408-414Article in journal (Refereed)
    Abstract [en]

    We have previously shown that the thrombin inhibiting agent melagatran markedly prolongs aPTT and counteracts creatinine increase in endotoxemic pigs. Against this background the effects of the platelet-inhibiting agent, clopidogrel on basic haemostatic, inflammatory and physiological variables were evaluated during porcine endotoxemia. Clopidogrel (10 mg/kg) or saline was randomly injected i.v. 30 min before start of a 6-h continuous infusion of endotoxin in 12 anaesthetised pigs. Another three pigs were given clopidogrel but not endotoxin. Clopidogrel did not affect physiological variables, formation of activated platelet microparticles, PK, aPTT, platelet count, plasma fibrinogen, TNF-alpha, or IL-6 during porcine endotoxemia. Although renal function, as evaluated by creatinine clearance (CLcr) deteriorated significantly (P = 0.01) in the saline-endotoxin, but not in the clopidogrel-endotoxin group, there was no significant difference between the saline-endotoxin and the clopidogrel-endotoxin groups. Renal biopsies were marked with a FITC-labelled chicken anti-fibrinogen antibody detecting fibrinogen and platelet bound fibrinogen, as a marker of porcine platelet activation, and examined by light microscopy. Evaluation of these immunohistochemical slides did not indicate that clopidogrel, significantly reduced the amount of intrarenal fibrin or fibrinogen depositions. Besides a trend to preserve renal function, clopidogrel did not affect haemodynamics or the coagulatory and inflammatory responses in porcine endotoxemia.

  • 43.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Olovsson, Matts
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Early endotoxin-mediated haemostatic and inflammatory responses in the clopidogrel-treated pig2005In: Platelets, ISSN 0953-7104, Vol. 16, no 7, p. 408-14Article in journal (Refereed)
  • 44.
    Mogensen, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Expected and experienced pain during epidural catheter insertion2014In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 2, p. 214-218Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Insertion of an epidural catheter for pain relief is frequently used in anaesthetic practice. Little is known regarding patients' expected vs. experienced pain and discomfort due to the epidural block procedure. The purpose of this study was to investigate the expected and experienced pain, respectively, associated with the epidural procedure in patients undergoing major abdominal surgery.

    METHODS: Thirty adult, unselected patients scheduled for elective major abdominal surgery were included in this study, which was approved by the ethics committee. Pre-operative insertion of an epidural catheter had to be a part of the anaesthetic routine procedure. Immediately before the epidural procedure, the patients were asked to grade the pain they expected from the procedure on an 11-point numeric rating system scale, ranging from 0 to 10, where '0' is no pain and '10' is worst imaginable pain. When the procedure had been carried out, the patients were once again asked to grade how much pain they had experienced.

    RESULTS: The median expected pain as a result of the epidural procedure was 5.0. Median experienced pain was 2.0. The median difference between the expected and experienced pain was -3.0 (P < 0.0001). The only patient who expected less pain than she subsequently experienced had a paraesthetic sensation. Gender, age, or previous experience from central neuraxial block did not significantly affect neither expected nor experienced pain.

    CONCLUSIONS: Patients expect significantly more pain than they experience from receiving an epidural block.

  • 45.
    Mutscher, Diana K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gustafsson, Urban
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders O
    Department of Medical Sciences.
    Eriksson, Mats
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Ropivacaine may have advantates cmpared to bupivacaine in porcine endotoxemic shock2005Other (Other (popular scientific, debate etc.))
  • 46. Mutschler, Diana K.
    et al.
    Lagrange, A.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wikström, G.
    Lind, L.
    Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordgren, Anders
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Myocardial inflammatory response in the endotoxaemic pig measured by microdialysis in vivo2001Other (Other academic)
  • 47.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lagrange, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wikström, G.
    Lind, L.
    Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Riksstämman 20012001Other (Other academic)
  • 48.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of mechanical ventilation on platelet microparticles in bronchoalveolar lavage fluid2002In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 108, no 4, p. 215-220Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Mechanical ventilation (MV) is considered to contribute to lung injury. Platelet membrane-derived microparticles (PMPs) are procoagulant and participate in the inflammatory process. The bronchoalveolar space could, besides plasma, be a site of origin of these microparticles. We evaluated the presence of these PMPs and two prostaglandin-derived metabolites in bronchoalveolar lavage fluid (BALF) regarding their possible relation to MV.

    MATERIALS AND METHODS: Before and after 1 h of MV, PMPs and prostaglandin metabolites were analyzed, in BALF from 14 anesthetized pigs, by flow cytometry and RIA, respectively. Tracheal mucus from five humans was analyzed for PMPs at extubation after surgery.

    RESULTS: Activated PMPs and prostaglandin metabolites were present in all BALF samples. The time needed to count 5000 cellular events was prolonged six-fold after 1 h of mechanical ventilation (p<0.001). The relative content of PMPs was constant in all samples. The PMPs were thrombogenic, i.e. they were fibrinogen, p-selectin and von Willebrand factor positive. Lavage did not per se affect the period necessary to count 5000 cellular events. PMPs in human tracheal mucus were in the same range as in the pig after 1 h of MV aiming at a PaCO(2) between 5.0 and 5.5 kPa.

    CONCLUSIONS: Activated PMPs are present in the pulmonary air-liquid interface. The prolongation of the time needed to count 5000 cellular events in BALF after MV indicates activation and adherence. Adherent microparticles bind neutrophils, which may aggravate pathological processes leading to pulmonary dysfunction. Evaluation of PMPs in BALF may be useful in evaluating strategies for lung-protective ventilator treatment.

  • 49.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lagrange, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig2006In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 26, no 9, p. 661-667Article in journal (Refereed)
    Abstract [en]

    To evaluate whether etanercept, a tumor necrosis factor (TNF)-blocking agent, may counteract hemodynamic deterioration in endotoxemic shock, we designed a prospective, randomized placebo-controlled trial with parallel groups, consisting of 13 pigs aged 10-14 weeks receiving general anesthesia. Five pigs were given 25 mg of etanercept, 1 h before the start of a 4-h continuous infusion of endotoxin. Another 5 pigs were given the corresponding volume of saline, 1 h before the start of a 4-h continuous infusion of endotoxin. Three pigs were given 25 mg of etanercept, 1 hr before the start of a 4-h continuous infusion of saline. At 1 h of endotoxemia, mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) increased identically in both groups of pigs receiving endotoxin. Thereafter, two distinct different patterns in hemodynamics were observed. TNF-blocked pigs showed significantly lower MPAP and PVRI compared to controls. In the etanercept-treated endotoxemic pigs, Doppler analysis of the diastolic mitral inflow demonstrated a significantly increased E/A-ratio (early mitral wave inflow was divided by the atrial wave) at 2 h. The TNFblocking agent etanercept normalized two hemodynamic features of endotoxin-induced septic shock in pigs: (1) the sustained pulmonary hypertension and (2) diastolic dysfunction.

  • 50.
    Ruge, Toralph
    et al.
    Department of Emergency and Internal Medicine, Skåne University Hospital, 214 28 Malmö, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tydén, Jonas
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Critical Care Medicine (Östersund), Umeå University, 901 87 Umeå, Sweden.
    Johansson, Joakim
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Critical Care Medicine (Östersund), Umeå University, 901 87 Umeå, Sweden.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    A Comparison between Endostatin and Conventional Biomarkers on 30-Day Mortality and Renal Replacement Therapy in Unselected Intensive Care Patients2021In: Biomedicines, E-ISSN 2227-9059, Vol. 9, no 11, article id 1603Article in journal (Refereed)
    Abstract [en]

    Endostatin may predict mortality and kidney impairment in general populations as well as in critically ill patients. We decided to explore the possible role of endostatin as a predictor of 30-day mortality, acute kidney injury (AKI), and renal replacement therapy (RRT) in a cohort of unselected intensive care unit (ICU) patients. Endostatin and creatinine in plasma were analyzed and SAPS3 was determined in 278 patients on ICU arrival at admission to a Swedish medium-sized hospital. SAPS3 had the highest predictive value, 0.85 (95% C.I.: 0.8–0.90), for 30-day mortality. Endostatin, in combination with age, predicted 30-day mortality by 0.76 (95% C.I.: 0.70–0.82). Endostatin, together with age and creatinine, predicted AKI with 0.87 (95% C.I.: 0.83–0.91). Endostatin predicted AKI with [0.68 (0.62–0.74)]. Endostatin predicted RRT, either alone [0.82 (95% C.I.: 0.72–0.91)] or together with age [0.81 (95% C.I.: 0.71–0.91)]. The predicted risk for 30-day mortality, AKI, or RRT during the ICU stay, predicted by plasma endostatin, was not influenced by age. Compared to the complex severity score SAPS3, circulating endostatin, combined with age, offers an easily managed option to predict 30-day mortality. Additionally, circulating endostatin combined with creatinine was closely associated with AKI development

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