Cerebral Protection during Controlled Hypoperfusion in a Piglet Model: Comparison of Moderate (25°C) versus Deep (18°C) Hypothermia at Various Flow Rates Using Intraoperative Measurements and Ex vivo Investigation

Abstract

Background During surgical correction of complex cardiac anomalies, some degree of hypoperfusion may be required. The aim of this study was to evaluate the effectiveness and safety of controlled cerebral hypoperfusion at moderate (25°C) versus deep (18°C) hypothermia.

Methods In this study, 56 female piglets (9.4 ± 0.8 kg, 3–4 weeks old) received cardiopulmonary bypass (CPB) at 25, 50, or 100% of the standard flow rate for 60 minutes of cardioplegic cardiac arrest. Body temperature was kept at 18, 25, and 37°C. Routine hemodynamic and functional parameters were measured online until 4 hours of reperfusion. Immunohistology was used to quantify heat shock protein 70 (HSP70) and nitrotyrosine (NO-Tyr) levels in the hippocampus; high-performance liquid chromatography was used to quantify jugular venous blood malondialdehyde (MDA) levels.

Results Reduced CPB flow led to significant reduction of mean arterial pressure by 79%, reduction of jugular venous oxygen saturation (S_vO₂) by 47%, reduction of carotid blood flow by 92%, and increase of serum lactate by 350%. All these changes were significantly enhanced in the 37°C versus the 25 and the 18°C groups. Regional oxygen saturation (rSO₂) was significantly reduced in the 37°C low flow groups. HSP70, NO-Tyr, and MDA were increased in the 25 and 50% flow groups (p < 0.05). There was a significant correlation between rSO₂ and S_vO₂ (r = 0.61) and between S_vO₂ and HSP70 (r = − 0.72).

Conclusions Reduction in global blood flow during CPB leads to comparable biochemical changes in the hippocampus at 25 and 18°C. Regional oxygenation saturation, S_vO₂, and HSP70 are important parameters to evaluate the efficacy of further anti-ischemic therapies during surgical corrections.

Keywords

brain protection - neuropsychological deficit - extracorporeal circulation - cardiac surgery

• References

• 1 Bellinger DC, Wypij D, Kuban KC , et al. Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. Circulation 1999; 100 (5) 526-532
• 2 Hövels-Gürich HH, Seghaye MC, Schnitker R , et al. Long-term neurodevelopmental outcomes in school-aged children after neonatal arterial switch operation. J Thorac Cardiovasc Surg 2002; 124 (3) 448-458
• 3 Bellinger DC, Jonas RA, Rappaport LA , et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med 1995; 332 (9) 549-555
• 4 Dunbar-Masterson C, Wypij D, Bellinger DC , et al. General health status of children with D-transposition of the great arteries after the arterial switch operation. Circulation 2001; 104 (12) (Suppl. 01) I138-I142
• 5 Forbess JM, Visconti KJ, Hancock-Friesen C, Howe RC, Bellinger DC, Jonas RA. Neurodevelopmental outcome after congenital heart surgery: results from an institutional registry. Circulation 2002; 106 (12) (Suppl. 01) I95-I102
• 6 Bellinger DC, Wypij D, duPlessis AJ , et al. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg 2003; 126 (5) 1385-1396
• 7 Likosky DS, Leavitt BJ, Marrin CAS , et al; Northern New England Cardiovascular Disease Study Group. Intra- and postoperative predictors of stroke after coronary artery bypass grafting. Ann Thorac Surg 2003; 76 (2) 428-434, discussion 435
• 8 Ganushchak YM, Fransen EJ, Visser C, De Jong DS, Maessen JG. Neurological complications after coronary artery bypass grafting related to the performance of cardiopulmonary bypass. Chest 2004; 125 (6) 2196-2205
• 9 Bucerius J, Gummert JF, Borger MA , et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg 2003; 75 (2) 472-478
• 10 Nollert G, Möhnle P, Tassani-Prell P , et al. Postoperative neuropsychological dysfunction and cerebral oxygenation during cardiac surgery. Thorac Cardiovasc Surg 1995; 43 (5) 260-264
• 11 Nollert G, Shin'oka T, Jonas RA. Near-infrared spectrophotometry of the brain in cardiovascular surgery. Thorac Cardiovasc Surg 1998; 46 (3) 167-175
• 12 Shin'oka T, Nollert G, Shum-Tim D, du Plessis A, Jonas RA. Utility of near-infrared spectroscopic measurements during deep hypothermic circulatory arrest. Ann Thorac Surg 2000; 69 (2) 578-583
• 13 Sakamoto T, Jonas RA, Stock UA , et al. Utility and limitations of near-infrared spectroscopy during cardiopulmonary bypass in a piglet model. Pediatr Res 2001; 49 (6) 770-776
• 14 Nollert G, Jonas RA, Reichart B. Optimizing cerebral oxygenation during cardiac surgery: a review of experimental and clinical investigations with near infrared spectrophotometry. Thorac Cardiovasc Surg 2000; 48 (4) 247-253
• 15 1996 NRC Guide for the Care and Use of Laboratory Animals. Available at: http://www.nap.edu/readingroom/books/labrats/contents.html . Accessed October 27, 2004
• 16 Paparella D, Brister SJ, Buchanan MR. Coagulation disorders of cardiopulmonary bypass: a review. Intensive Care Med 2004; 30 (10) 1873-1881
• 17 Speziale G, Ferroni P, Ruvolo G , et al. Effect of normothermic versus hypothermic cardiopulmonary bypass on cytokine production and platelet function. J Cardiovasc Surg (Torino) 2000; 41 (6) 819-827
• 18 Boldt J, Knothe C, Welters I, Dapper FL, Hempelmann G. Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ?. Ann Thorac Surg 1996; 62 (1) 130-135
• 19 Caputo M, Bays S, Rogers CA , et al. Randomized comparison between normothermic and hypothermic cardiopulmonary bypass in pediatric open-heart surgery. Ann Thorac Surg 2005; 80 (3) 982-988
• 20 Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995; 268 (5 Pt 1) L699-L722
• 21 Suzuki M, Tabuchi M, Ikeda M, Tomita T. Concurrent formation of peroxynitrite with the expression of inducible nitric oxide synthase in the brain during middle cerebral artery occlusion and reperfusion in rats. Brain Res 2002; 951 (1) 113-120
• 22 Sharp FR, Massa SM, Swanson RA. Heat-shock protein protection. Trends Neurosci 1999; 22 (3) 97-99
• 23 Mezrow CK, Gandsas A, Sadeghi AM , et al. Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest. J Thorac Cardiovasc Surg 1995; 109 (5) 959-975
• 24 Nollert G, Nagashima M, Bucerius J , et al. Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. II. hypoxic versus free radical injury. J Thorac Cardiovasc Surg 1999; 117 (6) 1172-1179
• 25 Anstadt MP, Stonnington MJ, Tedder M , et al. Pulsatile reperfusion after cardiac arrest improves neurologic outcome. Ann Surg 1991; 214 (4) 478-488 , discussion 489–490