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 degrees C) during cardiopulm onary bypass (CPB) in pigs reduce the physiologic and metabolic conseq uences of global cerebral ischemia. Methods: Sagittal sinus and cortic al microdialysis catheters were inserted into anesthetized pigs. Anima ls were placed on CPB and randomly assigned to 37 degrees C (n = 10), 34 degrees C (n = 10), 31 degrees C (n = 11), or 28 degrees C (n = 10) management. Next 20 min of global cerebral ischemia was produced by t emporarily Ligating the innominate and left subclavian arteries, follo wed 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 exc itatory amino acids (EAA) by microdialysis were measured using high-pe rformance liquid chromatography. Electroencephalographic (EEG) signals were graded by observers blinded to the protocol. After CPB, cerebros pinal fluid was sampled to test for S-100 protein and the cerebral cor tex was biopsied. Results: Cerebral oxygen metabolism increased after rewarming from 28 degrees C, 31 degrees C, and 34 degrees C CPB but no t in the 37 degrees animals; CMRO2 remained lower with 37 degrees C (1 .8 +/- 0.2 ml.min(-1).100 g(-1)) than with 28 degrees C (3.1 +/- 0.1 m l.min(-1).100 g(-1); P < 0.05). The EEG scores after CPB were depresse d in all groups and remained significantly lower in the 37 degrees C a nimals. With 28 degrees C and 31 degrees C CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischem ia at 37 degrees C and remained significantly greater during reperfusi on in the 34 degrees C and 37 degrees C groups. Cortical biopsy specim ens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37 degrees C animals. S-10 0 protein in cerebrospinal fluid was greater in the 37 degrees C (6 +/ - 0.9 mu g/l) and 34 degrees C (3.5 +/- 0.5 mu g/l) groups than the 31 degrees C (1.9 +/- 0.1 mu g/l) and 28 degrees C (1.7 +/- 0.2 mu g/l) animals. Conclusions: Hypothermia to 28 degrees C and 31 degrees C pro vides significant cerebral recovery from 20 ruin of global ischemia du ring CPB in terms of EAA release, EEG and cerebral metabolic recovery, and S-100 protein release without greater advantage from cooling to 2 8 degrees C compared with 31 degrees C. In contrast, ischemia during 3 4 degrees C and particularly 37 degrees C CPB showed greater EAA relea se and evidence of neurologic morbidity. Cooling to 31 degrees C was n ecessary to improve acute recovery during global cerebral ischemia on CPB.