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  • 1.
    Abrahamsson, Pernilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Åberg, Anna-Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Winsö, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Blind, Per Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Outcome of microdialysis sampling on liver surface and parenchyma2016Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 200, nr 2, s. 480-487Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To investigate whether surface microdialysis (μD) sampling in probes covered by a plastic film, as compared to noncovered and to intraparenchymatous probes, would increase the technique's sensitivity for pathophysiologic events occurring in a liver ischemia-reperfusion model. Placement of μD probes in the parenchyma of an organ, as is conventionally done, may cause adverse effects, e.g., bleeding, possibly influencing outcome.

    Methods: A transient ischemia-reperfusion model of the liver was used in six anesthetized normoventilated pigs. μD probes were placed in the parenchyma and on the liver surface. Surface probes were either left uncovered or were covered by plastic film.

    Results: Lactate and glucose levels were significantly higher in plastic film covered probes than in uncovered surface probes throughout the ischemic period. Glycerol levels were significantly higher in plastic film covered probes than in uncovered surface probes at 30 and 45 min into ischemia.

    Conclusions: Covering the μD probe increases the sensibility of the μD–technique in monitoring an ischemic insult and reperfusion in the liver. These findings confirm that the principle of surface μD works, possibly replacing need of intraparenchymatous placement of μD probes. Surface μD seemingly allows, noninvasively from an organ's surface, via the extracellular compartment, assessment of intracellular metabolic events. The finding that covered surface μD probes allows detection of local metabolic changes earlier than do intraparenchymatous probes, merit further investigation focusing on μD probe design.

  • 2. Acosta, Stefan
    et al.
    Nilsson, Torbjörn K
    Örebro universitet, Hälsoakademin.
    Malina, Janne
    Malina, Martin
    L-lactate after embolization of the superior mesenteric artery2007Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 143, nr 2, s. 320-328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Plasma markers for intestinal ischemia have not proven to be accurate. The value of L-lactate is unclear. Experimental models based on open surgery confound the effects of surgical trauma with that of ischemia. The aim was to create an endovascular model for acute superior mesenteric artery thromboembolism, and then to study L-lactate and lactate dehydrogenase (LD) activity in plasma and peritoneal fluid in pigs with extensive, high-grade intestinal ischemia. MATERIALS AND METHODS: Nine pigs underwent full superior mesenteric artery embolization with 4 h of intended intestinal ischemia, whereas six were control animals. Sampling of central venous and arterial blood was performed throughout the experiment, ending with laparotomy to collect peritoneal fluid and segmental intestinal biopsies. A pathologist, blinded to the performed interventions, graded the ischemic lesions. RESULTS: There were no differences in plasma L-lactate (P = 0.61) or LD activity levels (P = 0.69), measured at different time points from baseline to end of study, between animals with extensive, high-grade intestinal ischemia and sham. Intraperitoneal L-Lactate (P = 0.005) and LD activity (P = 0.018) levels were elevated compared with sham. There were differences in grades of ischemia in the duodenum (P = 0.003), small intestine (P < 0.001), proximal (P < 0.001), and sigmoid (P = 0.032) colon between experimental animals and sham. The grade of small bowel ischemia (n = 15) correlated to intraperitoneal fluid L-lactate (r = 0.80; P < 0.001) and LD activity levels (r = 0.72; P = 0.003). CONCLUSIONS: This endovascular study in a porcine model showed that L-lactate and LD activity levels in peritoneal fluid, not in plasma, reflect intestinal ischemia. The study suggests that plasma L-lactate not is a useful early marker in patients with suspicion of intestinal ischemia.

  • 3.
    Asif, Sana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Sedigh, Amir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Nordström, Johan
    Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Brandhorst, Heide
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Jorns, Carl
    Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Lorant, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Magnusson, Peetra U.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Nowak, Greg
    Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Theisinger, Sonja
    Novaliq GmbH, Heidelberg, Germany.
    Hoeger, Simone
    Department of Nephrology, Endocrinology and Rheumatology, University Medical Center Mannheim, Mannheim, Germany.
    Wennberg, Lars
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Brandhorst, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Oxygen-charged HTK-F6H8 emulsion reduces ischemia: reperfusion injury in kidneys from brain-dead pigs2012Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 178, nr 2, s. 959-967Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    Prolonged cold ischemia is frequently associated with a greater risk of delayed graft function and enhanced graft failure. We hypothesized that media, combining a high oxygen-dissolving capacity with specific qualities of organ preservation solutions, would be more efficient in reducing immediate ischemia-reperfusion injury from organs stored long term compared with standard preservation media.

    Methods:

    Kidneys retrieved from brain-dead pigs were flushed using either cold histidine-tryptophan-ketoglutarate (HTK) or oxygen-precharged emulsion composed of 75% HTK and 25% perfluorohexyloctane. After 18 h of cold ischemia the kidneys were transplanted into allogeneic recipients and assessed for adenosine triphosphate content, morphology, and expression of genes related to hypoxia, environmental stress, inflammation, and apoptosis.

    Results:

    Compared with HTK-flushed kidneys, organs preserved using oxygen-precharged HTK-perfluorohexyloctane emulsion had increased elevated adenosine triphosphate content and a significantly lower gene expression of hypoxia inducible factor-1 alpha, vascular endothelial growth factor, interleukin-1 alpha, tumor necrosis factor-alpha, interferon-alpha, JNK-1, p38, cytochrome-c, Bax, caspase-8, and caspase-3 at all time points assessed. In contrast, the mRNA expression of Bcl-2 was significantly increased.

    Conclusions:

    The present study has demonstrated that in brain-dead pigs the perfusion of kidneys with oxygen-precharged HTK-perfluorohexyloctane emulsion results in significantly reduced inflammation, hypoxic injury, and apoptosis and cellular integrity and energy content are well maintained. Histologic examination revealed less tubular, vascular, and glomerular changes in the emulsion-perfused tissue compared with the HTK-perfused counterparts. The concept of perfusing organs with oxygen-precharged emulsion based on organ preservation media represents an efficient alternative for improved organ preservation.

  • 4. Bertges, DJ
    et al.
    Berg, Sören
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Fink, MP
    Delude, RL
    Regulation of hypoxia-inducible factor 1 in enterocytic cells2002Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 160, s. 157-165Artikel i tidskrift (Refereegranskat)
  • 5.
    Björnsson, Bergthor
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Winbladh, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Bojmar, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Trulsson, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Sundqvist, Tommy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Gullstrand, Per
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis2012Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 176, nr 1, s. 55-62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Material and Methods. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceeded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Results. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC = 759 (84) mu M] and the IRI = 732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. Conclusions. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI.

  • 6. Bockhorn, Maximilian
    et al.
    Goralski, Michal
    Prokofiev, Dennis
    Dammann, Philipp
    Grünewald, Petra
    Trippler, Martin
    Biglarnia, Alireza
    Kamler, Markus
    Niehues, Eva M.
    Frilling, Andreja
    Broelsch, Christoph E.
    Schlaak, Jörg F.
    VEGF is important for early liver regeneration after partial hepatectomy2007Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 138, nr 2, s. 291-299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model.

    METHODS:

    To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel density (VD), vessel diameter (VDi), and intersinusoidal space, liver body weight ratio (LBR), hepatic proliferation and biochemical markers were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative RT-PCR.

    RESULTS:

    In the VEGF group, VD, VDi, and LBR were significantly increased compared with anti-VEGF or controls. Blockage of endogenous VEGF led to a marked increase of biochemical markers. Anti-VEGF almost completely suppressed and VEGF markedly enhanced hepatic proliferation in the first 24 h after surgery. This was associated with a modulation of cell cycle control genes (PC4, Gadd45a, Tis21/BTG2), v-jun, and CD14 by VEGF.

    CONCLUSIONS:

    VEGF plays an important role in liver regeneration and this may be due in part through its effects on neovascularization. Whether it may, when given therapeutically, represent a strategy to optimize liver regeneration in problematic patients needs to be clarified.

  • 7.
    Caballero-Corbalán, José
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Brandhorst, Heide
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Malm, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Felldin, Marie
    Foss, Aksel
    Salmela, Kaija
    Tibell, Annika
    Tufveson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Brandhorst, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation2012Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 175, nr 1, s. 163-168Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) has been established as an alternative to University-of-Wisconsin solution (UWS) for abdominal organ preservation, but data about HTK efficiency to preserve pancreata during prolonged cold ischemia time (CIT) are conflicting. In human islet transplantation, HTK provided similar isolation outcomes after short CIT. The present study aimed to investigate whether islets can be successfully isolated from HTK-preserved pancreata after prolonged CIT compared with UWS.

    MATERIALS AND METHODS: Sixty-four human pancreata retrieved from donors meeting criteria for kidney donation were perfused utilizing either HTK or UWS and preserved for more or less than 10 h prior to islet isolation. Along with parameters related to isolation and islet quality assessment, the dry-to-wet weight ratio was evaluated.

    RESULTS: Donor- and procurement-related factors did not vary between HTK- and UWS-perfused pancreata. The dry-to-wet weight ratio was lower in HTK-preserved pancreata indicated tissue edema (21.0% ± 3.5% versus 24.8% ± 2.0%, P = 0.007). Isolation-related variables differed between experimental groups after prolonged CIT with respect to purified packed tissue volume (9.1 ± 5.0 versus 17.2 ± 8.1 μL/g, P = 0.004) and islet yield (1910 ± 980 versus 3150 ± 1420 IE/g, P = 0.012). Islet purity and survival after culture were similar after HTK or UWS perfusion. The preservation solution did not affect in vitro function and transplantability of isolated islets.

    CONCLUSIONS: Compared with UWS, HTK has similar efficiency to preserve human pancreata for subsequent islet isolation during <10 h CIT but seems to be limited for prolonged cold storage.

  • 8.
    Dillström, Maria
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Bjerså, Kristofer
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Engström, My
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Patients' experience of acute unplanned surgical reoperation.2017Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 209, s. 199-205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Undergoing surgery always involves various risks of complications, often depending on the type of surgery. Because of complications, a second surgical intervention, a reoperation, must occasionally be done, which in turn often causes an extended hospital stay, a longer recovery phase, greater suffering for the patient, and higher health care costs. Even though complications after general surgery are relatively common, little is known regarding patient experience of a reoperation. Knowledge of this could impact on care models in the future. The aim of this study was to describe patients' experience of acute, unplanned reoperation during a planned hospital stay.

    MATERIALS AND METHODS: A purposive sampling strategy was used, and 16 patients were included, all who had undergone acute unplanned reoperation during a planned hospital stay. Semi-structured interviews were used to collect data, and a content analysis with an inductive approach was used for data analysis.

    RESULTS: The analysis resulted in two main themes: (1) health professionals' importance, having its foundation in categories trust and information, and (2) reaction, based on the categories anxiety and sadness.

    CONCLUSIONS: Unplanned reoperation caused psychological, social, and existential reactions. Health care professionals were perceived as important because good communication, accurate information, their presence, and creating feelings of confident and safe care were meaningful factors for the patients as they managed the situation.

  • 9.
    Edsberg, Lennart
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Natriuresis and the extracellular volume expansion by hypertonic saline2003Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 113, nr 1, s. 6-12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. The mechanisms governing the duration of the extracellular fluid volume (ECF) expansion as a result of intravenous infusion of hypertonic saline solution are poorly understood. We hypothesized that the duration is closely related to the sodium excretion. Materials and methods. Six conscious splenectomized ewes with a mean body weight of 30 kg were given an intravenous infusion of 4 ml kg(-1) of 7.5% saline solution on two occasions, one over a period of 5 min and another over a period of 20 min. Mass balance and volume kinetic calculations of the distribution and elimination of fluid were performed after repeated sampling of the plasma sodium concentration and the urinary excretion of water and sodium during 3 h. Results. On considering the addition of sodium to and its excretion from the body, the plasma sodium concentration indicated a 10% dilution of the extracellular space. The volume expansion decayed at an average rate of 20% of the volume expansion per hour, which, however, varied greatly in the animals, depending on their capacity to excrete sodium. After 1 h, increasing natriuresis promoted translocation. of water into the cells, which amounted to 25-35% of the total elimination. Computer simulations indicated that tripled natriuresis (up to approximately 750 mmol l(-1)) would increase the rate of elimination to 45% of the volume expansion per hour. Conclusion. The sodium excretion was inversely proportional to the duration of the extracellular volume expansion by 7.5% saline.

  • 10. Eguchi, Susumu
    et al.
    Lilja, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Hewitt, Winston R.
    Middleton, Yvette
    Demetriou, Achilles A.
    Rozga, Jacek
    Loss and recovery of liver regeneration in rats with fulminant hepatic failure1997Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 72, nr 2, s. 112-122Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased in weight four times reaching 30% of the original liver mass, the transplant-bearing rats expired due to inability of the regenerating liver to support the rat.

  • 11.
    Ewaldsson, Carl-Arne
    et al.
    South Hospital, Stockholm, Sweden.
    Vane, Luiz A.
    University of Texas Medical Branch, Galveston, USA.
    Kramer, George C.
    University of Texas Medical Branch, Galveston, USA.
    Hahn, Robert G.
    South Hospital, Stockholm, Sweden.
    Adrenergic drugs alter both the fluid kinetics and the hemodynamic responses to volume expansion in sheep2006Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 131, nr 1, s. 7-14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Plasma volume expansion is often performed during adrenergic therapy in the intensive care unit, but little is known about their combined effects.

    MATERIALS AND METHODS: The influence of three adrenergic drugs (50 microg/kg/min of dopamine, 0.1 microg/kg/min of isoprenaline, or 3 microg/kg/min of phenylephrine) on the relationship between plasma dilution (an index of volume expansion) and the central hemodynamic responses to volume loading with 24 ml/kg of 0.9% saline were evaluated in 6 adult sheep. Kinetic analysis was also applied to the data on plasma dilution and the urinary excretion measured during and after volume loading.

    RESULTS: The adrenergic agents markedly changed the baseline values for all hemodynamic parameters. The kinetic analysis showed that phenylephrine, which is an alpha-adrenergic receptor agonist, promoted renal excretion of infused fluid at the expense of fluid distribution to the periphery (P < 0.05 versus controls). Isoprenaline, which stimulates adrenergic beta-receptors, had the opposite effect. During volume expansion, cardiac atrial pressures increased by 25 to 90%, cardiac output by 13-80% and the arterial pressures by 2 to 22%. Plasma dilution during and after volume loading correlated, in a linear fashion, with these hemodynamic responses. The correlations were strong (r > 0.80) in the control and phenylephrine groups, but weaker in the dopamine and isoprenaline groups. Dopamine was associated with the most variable hemodynamic responses overall.

    CONCLUSIONS: Adrenergic drugs altered the hemodynamics at baseline (direct effects), changed the distribution and elimination of infused 0.9% saline (indirect effects) and, finally, modified most hemodynamic responses to plasma dilution (interaction effects).

  • 12.
    Friberg, B.
    et al.
    Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Heilborn, Berit
    Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Häggmark, Tom
    Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro universitet, Institutionen för medicinska vetenskaper. Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Food deprivation prior to stress reduces stimulated muscle force both before and after hemorrhage in the rat1994Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 16, nr 2, s. 131-137Artikel i tidskrift (Refereegranskat)
  • 13.
    Kiwanuka, Elizabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Hackl, Florian
    Caterson, Edward J.
    Nowinski, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Junker, Johan P. E.
    Gerdin, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Eriksson, Elof
    CCN2 is transiently expressed by keratinocytes during re-epithelialization and regulates keratinocyte migration in vitro by the ras-MEK-ERK signaling pathway2013Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 185, nr 2, s. E109-E119Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular protein that has numerous effects on cell life and cell interactions with the connective tissue. Although the importance of CCN2 for the fibrotic process in wound healing has been well studied, the involvement of CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of the present study was to investigate the role of CCN2 in the epidermis during wound healing. Materials and methods: Immunohistochemistry was done on sections from full-thickness porcine wounds. The effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK), and the effect of adding inhibitors to the ERK/ mitogen-activated protein kinase pathway to human keratinocytes were studied. Results: The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated protein kinase counteracted the effect of CCN2 on migration. Conclusions: CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway.

  • 14.
    Källskog, Örjan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Jansson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Autoregulation of Islet Graft Blood Flow Follows the Implantation2011Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 171, nr 2, s. 865-870Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Transplantation of pancreatic islets necessitates a revascularization, which is associated with a generalized graft vascular dysfunction, manifested, e.g., as a capillary hypertension, a decreased graft blood perfusion and graft hypoxia. Some of these changes can be due to impaired autoregulation of the newly formed vasculature in the islet grafts, and the aim of the present study was to further examine if this was the case.

    MATERIALS AND METHODS: We implanted 250 syngeneic islets under the renal capsule of rats and studied them 1 or 12-13 mo later. The blood perfusion of the whole kidney, renal cortex, and islet grafts were recorded in anesthetized animals with an ultrasound probe or laser-Doppler probes, respectively. The blood pressure in the kidneys was then gradually decreased by an adjustable clamp, during simultaneous measurement of blood flow values. RESULTS: The whole kidney, renal cortex, and islet grafts regulated their blood flow in concert with one another down to pressures of approximately 60 mmHg both 1 and 12-13 mo after implantation. However, the variability was greater at 1 mo.

    CONCLUSION: Islets transplanted under the renal capsule show similar autoregulatory properties with the kidney. It may be that the autoregulatory capacity of the renal interlobular arteries provides the underlying mechanism. This may be of importance for the good long-term survival of transplanted islets at this implantation site in experimental studies.

  • 15. Lund, Tormod
    et al.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Aursnes, Ingrid A
    Scholz, Hanne
    Foss, Aksel
    Rikshospitalet, Oslo.
    Sustained Reversal of Diabetes Following Islet Transplantation to Striated Musculature in the Rat2010Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 160, nr 1, s. 145-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: There is an increasing emphasis in the islet transplant community on the development of alternative sites for islet implantation. Striated musculature constitutes a potential alternative, which has been successfully employed in autotransplantation of parathyroid glands for decades. In the present study, a technique for intramuscular islet transplantation was developed and compared with intraportal islet transplantation in a syngeneic rat model. MATERIALS AND METHODS: Lewis rats were used. Pancreata were digested using Liberase. Islets were either transplanted into m. biceps femoris in a pearls-on-a-string fashion or intraportally, and the ability to reverse diabetes was compared. Eight weeks after transplantation an IVGTT was performed. Real-time quantitative RT-PCR was employed on muscle biopsies to investigate mRNA levels of cytokines in response to the transplant procedure. Explanted livers, muscles, and pancreata were harvested at the end of the experiment for histopathological analyses. RESULTS: 2000 IEQ repeatedly cured diabetic rats at the intraportal site, while 4000 IEQ was required at the intramuscular site. Time to reversal of diabetes, post-transplant weight development, and IVGTT curves did not differ between the groups. Normoglycemia was sustainable to the end of the study (>100 days) for all animals. The transplant procedure upregulated pro-inflammatory cytokines (IL-6 and IL-8) in striated muscle, and peri-islet fibrosis was observed in intramuscular grafts. CONCLUSIONS: Islet transplantation into striated musculature is feasible; however, in its present form the intramuscular site is less efficient compared with the liver in rats. The intramuscular site allows manipulation of the graft and implantation site prior to transplantation and may therefore have implications for islet transplantation in humans.

  • 16. Lundberg, J.
    et al.
    Razuvaev, A.
    Isaksson, B.
    Agustsson, T.
    Jonsson, Stefan
    KTH, Skolan för industriell teknik och management (ITM), Materialvetenskap.
    Holmin, S.
    Liver parenchyma access and lesion marker via the endovascular route2015Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 195, nr 2, s. 488-494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Neoadjuvant chemotherapeutic regimens for metastatic colorectal cancer are now so effective that they can cause "vanishing" lesions. With new advances such as local ablation, intra-arterial treatments in bolus with pumps or with beads, and isolation of hepatic perfusion, the need for a working channel to the liver may be warranted, ideally reducing the risk of spreading neoplastic cells. Materials and methods The endovascular trans-vessel wall Extroducer device makes it possible to gain direct access to the liver parenchyma. The distal tip is then detached, to act as both a marker and a securing plug in the vessel defect. We used ex vivo and in vivo tests to evaluate the device as a working channel for local administration of substances to the parenchyma and as a marker for detection with both transabdominal and intraoperative ultrasonography. Results We could deploy the Extroducer device without any hemorrhagic or thromboembolic complications in vivo, and we were able to detect all markers ex vivo and in vivo using both transabdominal and intraoperative ultrasonography. Furthermore, we found that it is possible to administer substances to the liver parenchyma using the catheter. Conclusions The trans-vessel wall technique can be used to establish a working channel to the liver parenchyma for administration of any substance, such as chemotherapeutic agents or cells. The detached device can also be used as a marker for ultrasound-guided partial liver resection in "vanishing lesions." The technique should have a low risk of seeding of neoplastic cells. This study in large animals forms a strong basis for translation to clinical studies.

  • 17.
    Macarak, Edward J.
    et al.
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Joan & Joel Rosenbloom Res Ctr Fibrot Dis, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA.
    Lotto, Christine E.
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Joan & Joel Rosenbloom Res Ctr Fibrot Dis, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Surg, Philadelphia, PA 19107 USA.
    Koganti, Deepika
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Joan & Joel Rosenbloom Res Ctr Fibrot Dis, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Surg, Philadelphia, PA 19107 USA.
    Jin, Xiaoling
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Joan & Joel Rosenbloom Res Ctr Fibrot Dis, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA.
    Wermuth, Peter J.
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Joan & Joel Rosenbloom Res Ctr Fibrot Dis, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA.
    Olsson, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Montgomery, Matthew
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Joan & Joel Rosenbloom Res Ctr Fibrot Dis, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA.
    Rosenbloom, Joel
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Joan & Joel Rosenbloom Res Ctr Fibrot Dis, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA.
    Trametinib prevents mesothelial-mesenchymal transition and ameliorates abdominal adhesion formation2018Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 227, s. 198-210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intra-abdominal adhesions are a major cause of morbidity after abdominal or gynecologic surgery. However, knowledge about the pathogenic mechanism(s) is limited, and there are no effective treatments. Here, we investigated a mouse model of bowel adhesion formation and the effect(s) of an Federal Drug Administration-approved drug (trametinib) in preventing adhesion formation. Materials and methods: C57BL/6 mice were used to develop a consistent model of intra-abdominal adhesion formation by gentle cecal abrasion with mortality rates of <10%. Adhesion formation was analyzed histologically and immunochemically to characterize the expression of pro-fibrotic marker proteins seen in pathologic scaring and included alpha smooth muscle actin (alpha SMA) and fibronectin EDA (FNEDA) which arises from alternative splicing of the fibronectin messenger RNA resulting in different protein isoforms. Trichrome staining assessed collagen deposition. Quantitative polymerase chain reaction analysis of RNA isolated from adhesions by laser capture microscopy was carried out to assess pro-fibrotic gene expression. To block adhesion formation, trametinib was administered via a subcutaneous osmotic pump. Results: Adhesions were seen as early as post-operative day 1 with extensive adhesions being formed and vascularized by day 5. The expression of the FNEDA isoform occurred first with subsequent expression of alpha SMA and collagen. The drug trametinib was chosen for in vivo studies because it effectively blocked the mesothelial to mesenchymal transition of rat mesothelium. Trametinib, at the highest dose used (3 mg/kg/d), prevented adhesion formation while at lower doses, adhesions were usually limited, as evidenced by the presence of FNEDA isoform but not alpha SMA. Conclusions: Cecal abrasion in mice is a reliable model to study abdominal adhesions, which can be ameliorated using the MEK1/2 inhibitor trametinib. While blocking adhesion formation at the cell and molecular levels, trametinib, at the therapeutic doses utilized, did not impair the wound healing at the laparotomy site. 

  • 18. Martinez-Alvarez, Concepcion
    et al.
    Gonzalez-Meli, Beatriz
    Berenguer-Froehner, Beatriz
    Paradas-Lara, Irene
    Lopez-Gordillo, Yamila
    Rodriguez-Bobada, Cruz
    Gonzalez, Pablo
    Chamorro, Manuel
    Arias, Pablo
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Casado-Gomez, Inmaculada
    Martinez-Sanz, Elena
    Injection and adhesion palatoplasty: a preliminary study in a canine model2013Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 183, nr 2, s. 654-662Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Raising mucoperiosteal flaps in traditional palatoplasty impairs mid-facial growth. Hyaluronic acid-based hydrogels have been successfully tested for minimally invasive craniofacial bone generation in vivo as carriers of bone morphogenetic protein-2 (BMP-2). We aimed to develop a novel flapless technique for cleft palate repair by injecting a BMP-2 containing hydrogel. Material and methods: Dog pups with congenital cleft palate were either non-treated (n = 4) or treated with two-flap palatoplasty (n = 6) or with the proposed injection/adhesion technique (n = 5). The experimental approach was to inject a hyaluronic acid-based hydrogel containing hydroxyapatite and BMP-2 subperiosteally at the cleft palate margins of pups aged six weeks. At week ten, a thin strip of the medial edge mucosa was removed and the margins were closed directly. Occlusal photographs and computed tomography (CT) scans were obtained up to week 20. Results: Four weeks after the gel injection the cleft palate margins had reached the midline and engineered bone had enlarged the palatal bones. Removal of the medial edge mucosa and suturing allowed complete closure of the cleft. Compared to traditional palatoplasty, the injection/adhesion technique was easier, and the post-surgical recovery was faster. CT on week 20 revealed some overlapping or "bending" of palatal shelves in the two-flap repair group, which was not observed in the experimental nor control groups. Conclusion: A minimally invasive technique for cleft palate repair upon injectable scaffolds in a dog model of congenital cleft palate is feasible. Results suggest better growth of palatal bones. This represents an attractive clinical alternative to traditional palatoplasty for cleft palate patients.

  • 19.
    Ogrinc, Greg
    et al.
    VA Outcomes Group, White River Junction VA Medical Center, White River Junction, Vermont.
    Davies, Louise
    VA Outcomes Group, White River Junction VA Medical Center, White River Junction, Vermont.
    Goodman, Daisy
    VA Outcomes Group, White River Junction VA Medical Center, White River Junction, Vermont.
    Batalden, Paul B.
    Högskolan i Jönköping, Hälsohögskolan, The Jönköping Academy for Improvement of Health and Welfare. Högskolan i Jönköping, Hälsohögskolan, HHJ. IMPROVE (Improvement, innovation, and leadership in health and welfare). Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
    Davidoff, Frank
    The Dartmouth Institute for Health Policy and Clinical Practice, Hanover, New Hampshire.
    Stevens, David
    The Dartmouth Institute for Health Policy and Clinical Practice, Hanover, New Hampshire.
    Standards for QUality Improvement Reporting Excellence 2.0: revised publication guidelines from a detailed consensus process2016Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 200, nr 2, s. 676-682Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Since the publication of Standards for QUality Improvement Reporting Excellence (SQUIRE 1.0) guidelines in 2008, the science of the field has advanced considerably. In this article, we describe the development of SQUIRE 2.0 and its key components. We undertook the revision between 2012 and 2015 using (1) semistructured interviews and focus groups to evaluate SQUIRE 1.0 plus feedback from an international steering group, (2) two face-to-face consensus meetings to develop interim drafts, and (3) pilot testing with authors and a public comment period. SQUIRE 2.0 emphasizes the reporting of three key components of systematic efforts to improve the quality, value, and safety of health care: the use of formal and informal theory in planning, implementing, and evaluating improvement work; the context in which the work is done; and the study of the intervention(s). SQUIRE 2.0 is intended for reporting the range of methods used to improve health care, recognizing that they can be complex and multidimensional. It provides common ground to share these discoveries in the scholarly literature (www.squire-statement.org).

  • 20.
    Sedigh, Amir
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Brännström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Magnusson, Peetra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Tufveson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Lorant, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Modifying the vessel walls in porcine kidneys during machine perfusion 2014Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 191, nr 2, s. 455-462Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Endothelial glycocalyx regulates the endothelial function and plays an active role in maintaining vascular homeostasis. During ischemia/reperfusion, the glycocalyx is rapidly shed into the blood stream. A heparin conjugate (CHC; Corline systems AB, Uppsala, Sweden) consists of 70 heparin molecules that have the capacity to adhere strongly to biological tissues expressing heparin affinity. We hypothesized that CHC could be used to restore disrupted glycocalyx in vivo in kidneys from brain-dead pigs.

    Materials and Methods: Brain death was induced in male landrace pigs (n=6) by inflating a balloon catheter in the epidural space until obtaining negative cerebral perfusion. The recovered kidneys (n=5+5) were perfused by hypothermic machine perfusion (HMP) using two Lifeport kidney transporters (Organ Recovery Systems, Chicago, IL, USA). 50 mg CHC (including 25 mg biotinylated CHC) or 50 mg unfractionated heparin (control) was added to the perfusion fluid in the respective machines. In one case, the kidneys were used only for dose escalation of CHC with the same procedure.

    Results: CHC was detected by immunofluorescence and confocal microscopy in the inner surface of vessel walls. The binding of CHC in the kidney was confirmed indirectly by consumption of CHC from the perfusion fluid.

    Conclusions: In this first attempt, we show that CHC may be used to coat the vessel walls of perfused kidneys during HMP, an approach that could become useful in restoring endothelial glycocalyx of kidneys recovered from deceased donors to protect vascular endothelium and possibly ameliorate ischemia/reperfusion injuries.

  • 21. Solberg, Anna
    et al.
    Holmdahl, Lena
    Falk, Peter
    Willén, Roger
    Palmgren, Ingrid
    Ivarsson, Marie-Louise
    Tissue Proteolysis in Appendicitis with Perforation2011Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 169, nr 2, s. 194-201Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Matrix metalloproteinases (MMPs) and serine proteases are able to degrade the extracellular matrix (ECM) and modulate immune responses in the gastrointestinal tract. The purpose of this study was to investigate local proteolysis in perforated appendicitis and its association with the appendix perforation.

    MATERIALS AND METHODS:

    Biopsies were taken at the sites of perforation (n = 15) and with a gradually increased distance from it. The expression and distribution of MMP-1, -2, and -9, the tissue inhibitor of metalloproteinases type (TIMP-1), plasminogen activator inhibitor type1 (PAI-1), and urokinase plasminogen activator (uPA) were measured by ELISA. The distribution of MMP-9, TIMP-1, uPA, and PAI-1 in perforated, nonperforated, and uninflamed appendix was investigated by immunohistochemistry with monoclonal antibody technique.

    RESULTS:

    MMP-1 expression was highest close to the perforation and was gradually decreased in biopsies in more distal locations (P < 0.01). MMP-9 showed a similar pattern being highest at the sites of perforation (P < 0.05), while MMP-2 expression showed a trend in the opposite direction without statistically significance. The expression of TIMP-1 trended lower at the sites of perforation. PAI-1 was highest at the sites of perforation (P < 0.01) and the uPA expression was similarly elevated close to and at the perforation.

    CONCLUSIONS:

    These data indicate a key role of MMP in the pathogenesis of appendix perforation. A local imbalance between MMP-9 and the inhibitor TIMP-1 could potentially contribute to the tissue injury leading to an appendix perforation. The overexpression of PAI-1 at the sites of perforation may also contribute to tissue damage.

  • 22. Suk Suh, K
    et al.
    Lilja, Helene
    Liver Support Research Laboratory, Department of Surgery, Burns and Allen Research Institute, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, 90048.
    Kamohara, Y
    Eguchi, S
    Arkadopoulos, N
    Neuman, T
    Demetriou, AA
    Rozga, J
    Bioartificial liver treatment in rats with fulminant hepatic failure: effect on DNA binding activity of liver-enriched and growth-associated transcription factors1999Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 85, nr 2, s. 243-250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobe necrosis. In FHF rats, lack of regeneration of the residual liver was associated with delayed expression of HGF and HGF receptor c-met and elevated blood HGF and TGF-β1 levels. We then found that intrasplenic hepatocyte transplantation prolonged survival in FHF rats and triggered hepatocyte proliferation in the native liver. The latter effect was associated with accelerated expression of HGF and c-met mRNA in the liver and lowering of blood HGF and TGF-β1 levels. In the present study we show that in FHF rats, treatment with a bioartificial liver (BAL) had similar effects.Materials and methods. FHF was induced in inbred Lewis rats and after 4 h, Group 1 rats were subjected to a 4-h whole blood perfusion through the BAL loaded with 3 × 108 microcarrier-attached syngeneic hepatocytes, whereas Group 2 control rats were treated with the BAL containing microcarriers only.Results. Compared to sham-BAL-treated rats, the test rats lived longer (28 ± 5 vs 17 ± 2 h; P = 0.0005), had better coagulation parameters, maintained higher body core temperature, and showed decreased plasma TGF-β1 levels. In addition, their liver remnants were HGF positive and showed increased DNA binding of transcription factors engaged in the modulation of hepatocyte proliferation (e.g., STAT3) and liver-specific gene expression (e.g., HNF1, HNF4, C/EBP).Conclusions. This study demonstrates that hepatocyte-based extracorporeal support not only can provide metabolic support by increasing the available functional liver mass but also is capable of modifying humoral and molecular mechanisms which are responsible for proliferation and organ-specific functions of residual hepatocytes.

  • 23. Tsai, Jon A
    et al.
    Lund, Mikael
    Lundell, Lars
    Nilsson Ekdahl, Kristina
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    One-lung ventilation during thoracoabdominal esophagectomy elicits complement activation2009Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 152, nr 2, s. 331-337Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. One-lung ventilation (OLV) during thoracoabdominal esophagectomy may induce an inflammatory response that can contribute to the induction and propagation of frequently occurring postoperative respiratory distress. Markers of such a response might be detected in the pulmonary as well as in the systemic circulation. Inflammation and tissue damage may be key pathogenetic pathways and we hypothesized that 1-lung ventilation may induce an inflammatory cascade reflected by markers for such a response. Materials and methods. Thirty patients with esophageal cancer were randomized to OLV (n = 16) or 2-lung ventilation (TLV; n = 14) during the thoracic part of the operation. Compounds involved in inflammation and coagulation were measured perioperatively and during the 1st, 2nd, 3rd, and 10th postoperative d. Results. During the perioperative phase, the proinflammatory cytokine interleukin-6 and thrombin, measured as thrombin-antithrombin complexes, started to increase. Thrombin, which can induce complement activation, peaked at the end of surgery and interleukin-6 at the 1st to 2nd postoperative d, but there were no differences between the OLV and TLV groups. C3a and terminal complement complex (TCC) started to increase on the 2nd postoperative d and continued to do so for the rest of the study period. The increase of TCC was significantly higher in the OLV group compared to the TLV group, whereas C3a attained similar levels in the 2 groups. Conclusions. OLV is associated with an augmented inflammatory response as reflected by the activation of the TCC. This may induce pulmonary tissue damage and recruitment of inflammatory cells.

  • 24. Tsai, Jon A.
    et al.
    Lund, Mikael
    Lundell, Lars
    Nilsson-Ekdahl, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    One-lung ventilation during thoracoabdominal esophagectomy elicits complement activation2009Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 152, nr 2, s. 331-337Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: One-lung ventilation (OLV) during thoracoabdominal esophagectomy may induce an inflammatory response that can contribute to the induction and propagation of frequently occurring postoperative respiratory distress. Markers of such a response might be detected in the pulmonary as well as in the systemic circulation. Inflammation and tissue damage may be key pathogenetic pathways and we hypothesized that 1-lung ventilation may induce an inflammatory cascade reflected by markers for such a response. MATERIALS AND METHODS: Thirty patients with esophageal cancer were randomized to OLV (n = 16) or 2-lung ventilation (TLV; n = 14) during the thoracic part of the operation. Compounds involved in inflammation and coagulation were measured perioperatively and during the 1st, 2nd, 3rd, and 10th postoperative d. RESULTS: During the perioperative phase, the proinflammatory cytokine interleukin-6 and thrombin, measured as thrombin-antithrombin complexes, started to increase. Thrombin, which can induce complement activation, peaked at the end of surgery and interleukin-6 at the 1st to 2nd postoperative d, but there were no differences between the OLV and TLV groups. C3a and terminal complement complex (TCC) started to increase on the 2nd postoperative d and continued to do so for the rest of the study period. The increase of TCC was significantly higher in the OLV group compared to the TLV group, whereas C3a attained similar levels in the 2 groups. CONCLUSIONS: OLV is associated with an augmented inflammatory response as reflected by the activation of the TCC. This may induce pulmonary tissue damage and recruitment of inflammatory cells.

  • 25.
    Winsnes, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Gunnarsson, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Falk, Peter
    Stark, Birgit
    Moskaug, Jan Ø.
    Strigård, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Evaluating full-thickness skin grafts in intraperitoneal onlay mesh position versus onlay position in mice2018Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 230, s. 155-163Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Importance: Hernia surgery requires reinforcement material with few side effects when used in the intraperitoneal position. Autologous skin grafting may meet this requirement, but animal experiments are obligatory before being applied in humans.

    OBJECTIVE: To compare survival and effects of isogeneic full-thickness skin grafts in the intraperitoneal onlay mesh (IPOM) position in mice, with a control group using the onlay position. Primary end point was graft survival and secondary end point adhesion formation and inflammation through NF-κB activity.

    METHODS: Design: Intervention study with 8-week follow-up in accordance with ARRIVE criteria, performed between 2015 and 2016.

    SETTING: Animal laboratory.

    PARTICIPANTS: Transgenic C57BL/6 mice with isogeneic background were used. Recipients were female wild-type phenotype mice >3 mo (n = 24). Donors were male or female mice >7 mo, with phenotype-positive for the luciferase gene (n = 20) or positive for NF-κB-luciferase gene (n = 4).

    INTERVENTION: Full-thickness skin was grafted in the IPOM position and compared with grafts in the onlay position as controls. Survival was evaluated by regular longitudinal postoperative luminescence imaging over 8 wk. Adherence formation was evaluated macroscopically after sacrifice. Inflammation of full-thickness skin grafts in IPOM position of NF-κB mice was evaluated in four additional mice. Main outcome and measure: Survival of grafts, evaluated by luminescence.

    RESULTS: Ten animals received grafts in the IPOM position, and 10 in the onlay position as controls. Graft survival after 8 wk was 100% (20/20). Average luminescence at the end of the 8-week period was 999,597 flux (min 162,800, max 2,521,530) in the IPOM group (n = 10) and 769,708 flux (min 76,590, max 2,164,080) in the onlay control group (n = 10). No adhesions requiring sharp dissection (Jenkins' scale >2) were seen. Four animals with grafts in the IPOM position showed peak inflammation (NF-κB activity) 5 d after surgery subsiding toward the end of follow-up.

    CONCLUSIONS: Full-thickness skin survives as well in the IPOM position as in the onlay control position, and few adherences develop. Further studies are required to fully characterize the tissue remodeling and repair processes associated with IPOM skin grafting. The result is relevant in the search for alternative reinforcement materials to be used in complex hernia surgery in humans.

  • 26. Zaitoun, AA
    et al.
    Apelqvist, G
    Al-Mardini, H
    Gray, T
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi.
    Record, CO
    Quantitative studies of liver atrophy after portacaval shunt in the rat2006Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 131, nr 2, s. 225-232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. It is well known that portacaval shunting ultimately leads to a decrease in liver volume and hepatic function, but the mechanism is uncertain. The aim of the present study was to evaluate the effect of portacaval shunting (PCS) upon the morphological changes that occur in the liver in rats after port caval. anastomosis. Materials and methods. Sixty-six male rats underwent either PCS (n = 35) or sham operations (n = 31). Hormone levels were determined in blood samples taken just before removal and weighing of the livers. Hematoxylin and eosin-stained sections were used for quantitative morphometric analysis. Apoptosis, mitosis, and cellular organelles also were assessed quantitatively. Results. There was a significant reduction in the liver mass together with testosterone levels in PCS rats in comparison with sham rats. The distance between presinusoidal and postsinusoidal vessels was reduced from 500 mu m in the sham rats to 299 mu m in the PCS rats (P = 0.000001). Within the same group, there was a significant reduction in the area of hepatocyte nuclei in zone 3 in comparison with zone 1. Electron microscopy revealed a highly significant (P = 0.0007) reduction in the membrane-bound cytoplasmic organelles of zone 3 hepatocytes in PCS rats in comparison with the sham rats. Apoptosis was increased in zone 3 in PCS rats (P = 0.00001), whereas in zone 1 of the same group, there was an associated increased in mitosis (P = 0.000001). Overall, the degree of apoptosis was in excess of mitosis, resulting in a general loss of liver mass. Conclusion. Morphometric analysis at cellular and subcellular levels confirms the morphological findings of liver atrophy in PCS rats. The mechanism of atrophy is a complex one. Portacaval shunting leads to hepatic atrophy that, in turn, results in microcirculatory and hormonal changes that further contribute to liver cell loss in this animal model. (C) 2006 Elsevier Inc. All rights reserved.

  • 27.
    Åkesson, Oscar
    et al.
    Dept of Clinical Scienses, Lund University.
    Abrahamsson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Blind, Per-Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Surface microdialysis on small bowel serosa in monitoring of ischemia2016Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 204, nr 1, s. 39-46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Ischemic injury of an organ causes metabolic change from aerobic to anaerobic metabolism. It has been shown in experimental studies on the heart and liver that such conversion may be detected by conventional microdialysis probes placed intraparenchymatously, as well as on organ surfaces, by assaying lactate, pyruvate, glucose, and glycerol in dialysate. We developed a microdialysis probe (S-mu D) intended for use solely on organ surfaces. The aim of this study was to assess whether the newly developed S-mu D probe could be used for detection and monitoring of small bowel ischemia. Methods: In anesthetized normoventilated pigs, a control S-mu D probe was applied on the jejunal serosa 50 cm downstream from the duodenojejunal junction (DJJ). Starting 100 cm from DJJ, a 100-cm long ischemic segment was created by division of all mesenteric vessels. S-mu Ds were applied at 2.5, 5, 20, and 50 cm from the starting point of ischemia by serosal sutures. A standard mu D probe was placed in the abdominal cavity as a further control. Dialysate was harvested before inducing ischemia and subsequently every 20 min for 4 h. Central venous blood was drawn every hour to monitor systemic lactate, C-reactive protein, and white blood cell count. Results: Microdialysis lactate levels were significantly higher than baseline from 20 min on into protocol time in the ischemic segment and in the control S-mu D probe. The peritoneal cavity probe showed no significant elevation. Lactate levels from the ischemic segment reached a plateau at 60 min. Courses of pyruvate, glucose, and glycerol levels were in accordance with transition from an aerobic to anaerobic metabolism in the bowel wall. No statistically significant changes in hemoglobin, white blood cell count, or lactate values in central venous blood were recorded. Conclusions: Assaying the aforementioned compounds in dialysate, harvested by the newly developed S-mu D probe, allowed detection and monitoring of small bowel ischemia from 20 min on following its onset.

  • 28.
    Åkesson, Oscar
    et al.
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Falkenback, Dan
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Abrahamsson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Surface Microdialysis Detects Ischemia After Esophageal Resection: An Experimental Animal Study2019Ingår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 245, s. 537-543Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: After an esophageal resection, continuity is commonly restored by a gastric tube reconstruction and an intrathoracic anastomosis to the remaining proximal esophagus. Ischemia of the anastomotic region is considered to play a pivotal role in anastomotic leakage. Microdialysis (μD) is an excellent method to measure local biochemical substances and parameters in a specific organ or compartment aiming at early detection of ischemia. This animal study evaluates ischemia of the gastric tube reconstruction using a novel method-μD on organ surfaces. This promising method may have the potential to detect an anastomotic leakage before clinical symptoms develop.

    METHODS: Anesthetized normoventilated pigs were used. Surface microdialysis (S-μD) catheters and an intraparenchymal oxygen tension catheter were placed on the stomach. A gastric tube was made and the gastroepiploic artery was divided halfway along the greater curvature to produce severe ischemia at the top of the gastric tube. μD data from four locations (gastric tube, ileum and peritoneal cavity) were recorded every 20 min during the experiment. Tissue samples from all catheter sites underwent histopathological analysis. Intraparenchymal oxygen partial pressure, systemic blood tests, and hemodynamic parameters were recorded.

    RESULTS: S-μD data showed values indicating severe ischemia at the top of the gastric tube and intermediate ischemia at the level of transection of the gastroepiploic artery. Ischemia was verified by histopathological analysis of tissue samples and intraparenchymal oxygen tension data.

    CONCLUSIONS: S-μD can detect and grade severity of local ischemia in real time, in an animal model.

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