Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs

Background: The aim of this study was to determine whether progressive levels of hypothermia (37, 34, 31, or 28°C) during cardiopulmonary bypass (CPB) in pigs reduce the physiologic and metabolic consequences of global cerebral ischemia. Methods: Sagittal sinus and cortical microdialysis catheters were inserted into anesthetized pigs. Animals were placed on CPB and randomly assigned to 37°C (n = 10), 34°C (n = 10), 31°C (n = 11), or 28°C (n = 10) management. Next 20 min of global cerebral ischemia was produced by temporarily ligating the innominate and left subclavian arteries, followed by reperfusion, rewarming, and termination of CPB. Cerebral oxygen metabolism (CMRO₂) was calculated by cerebral blood flow (radioactive microspheres) and arteriovenous oxygen content gradient. Cortical excitatory amino acids (EAA) by microdialysis were measured using high-performance liquid chromatography. Electroencephalographic (EEG) signals were graded by observers blinded to the protocol. After CPB, cerebrospinal fluid was sampled to test for S-100 protein and the cerebral cortex was biopsied. Results: Cerebral oxygen metabolism increased after rewarming from 28°C, 31°C, and 34°C CPB but not in the 37°animals; CMRO₂ remained lower with 370C (1.8 ± 0.2 ml · min^-1 · 100 g^-1) than with 28°C (3.1 ± 0.1 ml · min^-1 · 100 g^-1; p < 0.05). The EEG scores after CPB were depressed in all groups and remained significantly lower in the 37°C animals. With 28°C and 31°C CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischemia at 37°C and remained significantly greater during reperfusion in the 34°C and 37°C groups. Cortical biopsy specimens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37°C animals. S-100 protein in cerebrospinal fluid was greater in the 37°C (6 ± 0.9 μg/l) and 34°C (3.5 ± 0.5 μg/l) groups than the 31°C (1.9 ± 0.1 μg/l) and 28°C (1.7 ± 0.2 μg/l) animals. Conclusions: Hypothermia to 28°C and 31°C provides significant cerebral recovery from 20 min of global ischemia during CPB in terms of EAA release, EEG and cerebral metabolic recovery, and S-100 protein release without greater advantage from cooling to 28°C compared with 31°C. In contrast, ischemia during 34°C and particularly 37°C CPB showed greater FAA release and evidence of neurologic morbidity. Cooling to 31°C was necessary to improve acute recovery during global cerebral ischemia on CPB.