Improved Cerebral Resuscitation From Cardiac Arrest in Dogs With Mild Hypothermia Plus Blood Flow Promotion

Abstract

Background and Purpose In past studies, cerebral outcome after normothermic cardiac arrest of 10 or 12.5 minutes in dogs was improved but not normalized by resuscitative (postarrest) treatment with either mild hypothermia or hypertension plus hemodilution. We hypothesized that a multifaceted combination treatment would achieve complete cerebral recovery. Methods With our established dog outcome model, normothermic ventricular fibrillation of 11 minutes (without blood flow) was followed by controlled reperfusion (with brief normothermic cardiopulmonary bypass simulating low flow and low Pa o 2 of external cardiopulmonary resuscitation) and defibrillation at <2 minutes. Controlled ventilation was provided to 20 hours and intensive care to 96 hours. Control group 1 (n=8) was kept normothermic (37.5°C), normotensive, and hypocapnic throughout. Experimental group 2 (n=8) received mild resuscitative hypothermia (34°C) from about 10 minutes to 12 hours (by external and peritoneal cooling) plus cerebral blood flow promotion with induced moderate hypertension, mild hemodilution, and normocapnia. Results All 16 dogs in the protocol survived. At 96 hours, all 8 dogs in control group 1 achieved overall performance categories 3 (severe disability) or 4 (coma). In group 2, 6 of 8 dogs achieved overall performance category 1 (normal); 1 dog achieved category 2 (moderate disability), and 1 dog achieved category 3 ( P <.001). Final neurological deficit scores (0% [normal] to 100% [brain death]) at 96 hours were 38±10% (22% to 45%) in group 1 versus 8±9% (0% to 27%) in group 2 ( P <.001). Total brain histopathologic damage scores were 138±22 (110 to 176) in group 1 versus 43±9 (32 to 56) in group 2 ( P <.001). Regional scores showed similar group differences. Conclusions After normothermic cardiac arrest of 11 minutes in dogs, resuscitative mild hypothermia plus cerebral blood flow promotion can achieve functional recovery with the least histological brain damage yet observed with the same model and comparable insults.