Prolonged deep hypothermic circulatory arrest in rats can be achieved without cognitive deficits.

Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) enable surgical repair of cardiovascular defects. However, neurological complications can result after both CPB and DHCA. We sought to investigate if 75 min of CPB or DHCA caused motor, cognitive or histological deficits in rats. Three groups were studied: DHCA, CPB, and sham. Rats in the DHCA group were subjected to 75 min DHCA at 15 degrees C, with a total CPB duration of 75 min. Rats in the CPB group were subjected to 75 min of normothermic CPB. Shams received the same anesthesia, cannulations and infusions. Motor function was assessed using beam testing on days 3-13. Cognitive performance was evaluated using Morris water maze tasks on days 7-13. Overall Performance Category (OPC) and Neurologic Deficit Score (NDS) were assessed daily. Histological Damage Score (HDS) was assessed in survivors on day 14. Sustained deficits on beam testing were seen only in the CPB group. Rats in the CPB and DHCA groups exhibited similar cognitive performance vs. sham. There were no differences in OPC or NDS between groups. Neuronal degeneration was present only in small foci in rats after DHCA (n=4/7). However, HDS was not different in individual brain regions or viscera between DHCA or CPB vs. sham. Surprisingly, CPB, but not DHCA was associated with motor deficits vs. sham, and no cognitive deficits were seen in either group vs. sham. Future studies with longer DHCA duration will be necessary to provide targets to assess novel preservation strategies.

Profound hypothermia is superior to ultraprofound hypothermia in improving survival in a swine model of lethal injuries.

BACKGROUND: Rapid induction of profound hypothermia can improve survival from uncontrolled lethal hemorrhage. However, the optimal depth of hypothermia in this setting remains unknown. This experiment was designed to compare the impact of deep (15 degrees C), profound (10 degrees C), and ultraprofound (5 degrees C) hypothermia on survival and organ functions. METHODS: Uncontrolled lethal hemorrhage was induced in 32 swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 minutes later by laceration of the descending thoracic aorta. Hypothermia was induced rapidly (2 degrees C/min) by infusing cold organ preservation solution into the aorta through a thoracotomy. The experimental groups were (n = 8 per group): a normothermic control, and 3 hypothermic groups in which the core temperature was reduced to 15 degrees C, 10 degrees C, and 5 degrees C. Vascular injuries were repaired during 60 minutes of hypothermia. Animals were then rewarmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass, and monitored for 6 weeks for neurologic deficits, cognitive function, and organ dysfunction. RESULTS: All normothermic animals died, whereas 6-week survival rates for the 15 degrees C, 10 degrees C, and 5 degrees C groups were 62.5%, 87.5%, and 25%, respectively (P < .05: normothermic vs 15 degrees C and 10 degrees C; 10 degrees C vs 5 degrees C). The surviving animals from the 15 degrees C and 10 degrees C groups were neurologically intact, displayed normal learning capacity, and had no long-term organ dysfunction. The survivors from the 5 degrees C group displayed slower recovery and impaired cognitive functions. CONCLUSIONS: In a model of lethal injuries, rapid induction of profound hypothermia can prevent death. The depth of hypothermia influences survival, with a better outcome associated with a core temperature of 10 degrees C compared with 5 degrees C.