Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs

Abstract

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.