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 degree sign] Celsius) 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 degree sign] Celsius (n = 10), 34 degree sign] Celsius (n = 10), 31 degree sign] Celsius (n = 11), or 28 degree sign] Celsius (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 degree sign] Celsius, 31 degree sign] Celsius, and 34 degree sign] Celsius CPB but not in the 37 degree sign] animals; CMRO2, remained lower with 37 degree sign] Celsius (1.8 +/- 0.2 ml center dot] min sup -1 center dot] 100 g sup -1) than with 28 degree sign] Celsius (3.1 +/- 0.1 ml center dot] min sup -1 center dot] 100 g sup -1; P < 0.05). The EEG scores after CPB were depressed in all groups and remained significantly lower in the 37 degree sign] Celsius animals. With 28 degree sign] Celsius and 31 degree sign] Celsius CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischemia at 37 degree sign] Celsius and remained significantly greater during reperfusion in the 34 degree sign] Celsius and 37 degree sign] Celsius groups. Cortical biopsy specimens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37 degree sign] Celsius animals. S-100 protein in cerebrospinal fluid was greater in the 37 degree sign] Celsius (6 +/- 0.9 micro gram/l) and 34 degree sign] Celsius (3.5 +/- 0.5 micro gram/l) groups than the 31 degree sign] Celsius (1.9 +/- 0.1 micro gram/l) and 28 degree sign] Celsius (1.7 +/- 0.2 micro gram/l) animals.