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Cerebral Perfusion and Metabolism during Experimental Extracorporeal Circulation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neurologic injuries are major causes of mortality and morbidity after cardiac surgery. This thesis aimed to investigate cerebral metabolism and perfusion abnormalities in pigs during hypothermic circulatory arrest, selective antegrade cerebral perfusion (SACP) and extracorporeal circulation following progressive venous stasis.

Hypothermic circulatory arrest induced a metabolic pattern consistent with overt ischaemia, which was absent following SACP. In contrast, metabolism during SACP was influenced by the perfusate temperature, where a colder perfusate (20 °C) preserved cellular metabolism and membrane integrity better than a warmer perfusate (28 °C).

The minimum SACP flow required to maintain metabolism during hypothermia at 20 °C was investigated with magnetic resonance imaging, protein S100β, near infrared spectroscopy and microdialysis. The findings suggested an ischaemic threshold close to 6 ml/kg/min in the present models. Furthermore, regional differences in perfusion with a hemispheric distribution were apparent at all flow levels and differed from earlier studies where the differences were uniform and followed a neuranatomical pattern.

Venus stasis following superior vena cava congestion produced measurable signs of impaired cerebral perfusion and patterns of cerebral ischaemia were evident in individual animals. As venous pressure increased, the mean arterial pressure stayed more or less unchanged, generating reduced cerebral perfusion pressure and consequently an increased risk of ischaemia, which may impair cerebral perfusion, especially in cases of compromised arterial flow during extracorporeal circulation.

In conclusion, cerebral metabolism and perfusion are influenced by temperature, SACP flow levels and venous congestion. In clinical practice, the regional differences in perfusion during SACP may be of pathogenic importance in focal cerebral ischaemia. Furthermore, the reduced superior vena cava cannula flow may pass undetected during bicaval cardiopulmonary bypass if the superior vena cava flow is not specifically monitored.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 85 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 649
Keyword [en]
cerebral perfusion
National Category
Physiology
Research subject
Thorax Surgery
Identifiers
URN: urn:nbn:se:uu:diva-147486ISBN: 978-91-554-8016-5OAI: oai:DiVA.org:uu-147486DiVA: diva2:400464
Public defence
2011-04-08, Enghovssalen, Hus 50,, Thoraxkliniken, Akademiska Sjukuset, 17185, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Funder
Swedish Research Council
Available from: 2011-03-17 Created: 2011-02-25 Last updated: 2011-05-04Bibliographically approved
List of papers
1. Microdialysis and tissue oxygenation predicts safe arterial blood flow during cerebral perfusion
Open this publication in new window or tab >>Microdialysis and tissue oxygenation predicts safe arterial blood flow during cerebral perfusion
(English)Article in journal (Refereed) Submitted
Abstract [en]

Background

The optimal blood flow level for selective antegrade cerebral perfusion (SACP) has not been established. Based on experimental data, an arterial flow below 6 mL/kg/min may be associated with ischemia at 20 °C. To evaluate this possible ischemic threshold, cerebral metabolism was evaluated using microdialysis from the cerebral parenchyma and sagittal sinus at SACP levels of 4 and 6 mL/kg/min.

Methods

Pigs on 20 °C cardiopulmonary bypass (CPB) were assigned to Groups 1-3. In Group 1, SACP was initiated at 4 mL/kg/min and followed by 6 mL/kg/min for 60 + 60 min, respectively. In Group 2, the order was reversed from 6 to 4 mL/kg/min. Group 3 continued on CPB as controls. Cerebral near-infrared spectroscopy was measured continuously while cerebral and sagittal sinus microdialysis samples were analyzed every 30 min.

Results

The tissue oxygenation index was significantly lower in Group 1 compared with Groups 2 and 3 at 90-120 min (p=0.007) and the cerebral lactate/pyruvate ratio was significantly greater at 120 minutes in Group 1 compared to Groups 2 and 3 (p=0.008). Glycerol in the sagittal sinus blood was significantly elevated at 120 min in Groups 1 and 2 compared to the control (p<0.0001). There was no agreement between microdialysis biomarker levels in the brain parenchyma and sagittal sinus blood.

Conclusions

SACP at 6 mL/kg/min preserved metabolism in the present model, whereas at 4 mL/kg/min early signs of disturbed energy metabolism were seen. Microdialysis from the sagittal sinus is feasible but no agreement with parenchymal measurements could be demonstrated.

Keyword
cerebral perfusion
National Category
Physiology
Research subject
Thorax Surgery
Identifiers
urn:nbn:se:uu:diva-147481 (URN)
Available from: 2011-02-25 Created: 2011-02-25 Last updated: 2011-03-30
2. Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade
Open this publication in new window or tab >>Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade
Show others...
2011 (English)In: Annals of Thoracic Surgery, ISSN 0003-4975, Vol. 91, no 4, 1198-1205 p.Article in journal (Refereed) Published
Abstract [en]

Background

Selective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig.

Methods

Two groups of pigs were subjected to SACP at 20°C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg−1 · min−1 and in group 2 (n = 5), flow was kept constant at 6 mL · kg−1 · min−1. Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100β was measured in peripheral blood.

Results

Decreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg−1 · min−1. No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100β were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP.

Conclusions

The findings suggest an ischemic threshold close to 6 mL · kg−1 · min−1 in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.

Keyword
cerebral perfusion
National Category
Physiology
Research subject
Thorax Surgery
Identifiers
urn:nbn:se:uu:diva-147480 (URN)10.1016/j.athoracsur.2010.12.066 (DOI)000288785800057 ()21353198 (PubMedID)
Funder
Swedish Research Council, k2010-64x-08268-23-3
Available from: 2011-02-25 Created: 2011-02-25 Last updated: 2013-08-28Bibliographically approved
3. Venous obstruction and cerebral perfusion during experimental cardiopulmonary bypass
Open this publication in new window or tab >>Venous obstruction and cerebral perfusion during experimental cardiopulmonary bypass
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2010 (English)In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 11, no 5, 561-566 p.Article in journal (Refereed) Published
Abstract [en]

To investigate the effects on cerebral perfusion by experimental venous congestion of the superior vena cava (SVC) during bicaval cardiopulmonary bypass (CPB) at 34 °C, pigs were subjected to SVC obstruction at levels of 75%, 50%, 25% and 0% of baseline SVC flow at two arterial flow levels (low, LQ, high, HQ). The cerebral perfusion was examined with near-infrared spectroscopy (NIRS), cerebral microdialysis and blood gas analysis. SVC obstruction caused significant decreases in the NIRS tissue oxygenation index (TOI) and in SVC oxygen saturations (P<0.05, both groups), while the mixed venous saturation was decreased only in the LQ group. Sagittal sinus venous saturations were measured in the HQ group and found significantly reduced in response to venous congestion (P<0.05). No microdialysis changes were seen at the group level, however, individual ischemic patterns in terms of concomitant venous desaturation, decreased TOI and increased lactate/pyruvate occurred in both groups. The total venous drainage remained stabile throughout the experiment, indicating increased flow in the inferior vena cava cannula. The results indicate that SVC congestion may impair cerebral perfusion especially in the case of compromised arterial flow during CPB. Reduced SVC cannula flow may pass undetected during bicaval CPB, if SVC flow is not specifically monitored.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-140803 (URN)10.1510/icvts.2010.238535 (DOI)000208483300014 ()20696750 (PubMedID)
Available from: 2011-01-10 Created: 2011-01-10 Last updated: 2015-06-30Bibliographically approved
4. Selective antegrade cerebral perfusion at two different temperatures compared to hypothermic circulatory arrest: an experimental study in the pig with microdialysis
Open this publication in new window or tab >>Selective antegrade cerebral perfusion at two different temperatures compared to hypothermic circulatory arrest: an experimental study in the pig with microdialysis
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2009 (English)In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 8, no 6, 647-653 p.Article in journal (Refereed) Published
Abstract [en]

Hypothermic arrest and selective antegrade cerebral perfusion (SACP) is widely used during aortic arch surgery. The microdialysis technique monitors biomarkers of cellular metabolism and cellular integrity over time. In this study, the cerebral changes during hypothermic circulatory arrest (HCA) at 20 degrees C and HCA with SACP at two different temperatures, 20 and 28 degrees C, were monitored. Twenty-three pigs were divided into three groups. A microdialysis probe was fixated into the forebrain. Circulatory arrest started at a brain and body temperature of 20 degrees C or 28 degrees C. Arrest with/without cerebral perfusion (flow 10 ml/kg, max carotid artery pressure 70 mmHg) lasted for 80 min followed by reperfusion and rewarming during 40 min and an observation period of 120 min. The microdialysis markers were registered at six time-points. The lactate/pyruvate ratio (L/P ratio) and the lactate/glucose ratio (L/G ratio) increased significantly (P<0.05), during arrest, in the HCA group. The largest increase of glycerol was found in the group with tepid cerebral perfusion (28 degrees C) and the HCA group (P<0.05). This study supports the use of SACP over arrest. It also suggests that cerebral metabolism and cellular membrane integrity may be better preserved with SACP at 20 degrees C compared to 28 degrees C.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-110757 (URN)10.1510/icvts.2008.200048 (DOI)19324918 (PubMedID)
Available from: 2009-11-24 Created: 2009-11-24 Last updated: 2015-06-12Bibliographically approved

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