Effects of Different Hypothermia on the Results of Cardiopulmonary Resuscitation in a Cardiac Arrest Rat Model

Abstract

Objective. To investigate the optimal temperature of hypothermia treatment in rats with cardiac arrest caused by ventricular fibrillation (VF) after the return of spontaneous circulation (ROSC). Methods. A total of forty-eight male Sprague-Dawley rats were induced by VF through the guidewire with a maximum of 5 mA current and untreated for 8 min. Cardiopulmonary resuscitation (CPR) was performed for 8 min followed by defibrillation (DF). Resuscitated rats were then randomized into the normothermia (37°C) group, milder (35°C) group, mild (33°C) group, or moderate (28°C) group. Hypothermia was immediately induced with surface cooling. The target temperature was maintained for 4 h before rewarming to $37\pm {0.5}^{°}\text{C}$ . Moreover, at the end of the 4 h, a rat in each group was randomly selected to be sacrificed for the cerebral cortex electron microscopy observation ( $n=1$ ). The other resuscitated animals were observed for up to 72 h after ROSC ( $n=7$ ). Left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume (LVEDV) were measured. Survival time, survival rate, and neurological deficit score (NDS) were recorded for 72 h. Results. During hypothermia, higher LVEF was observed in the hypothermia groups when compared with normothermia group (35°C vs. 37°C, $p<0.05$ , 33°C and 28°C vs. 37°C, $p<0.01$ ). Among the hypothermia groups, LVEF was higher in the 28°C group than that of 35°C ( $p<0.05$ ). However, both the heart rate (HR) ( $p<0.01$ ) and LVEDV (28°C vs. 35°C, $p<0.01$ , 28°C vs. 37°C and 33°C, $p<0.05$ ) were lowest in the 28°C group when compared with the other groups. There were no significant differences of LVEF and LVEDV between the group 35°C and 33°C ( $p>0.05$ ). After rewarming, the LVEF of 35°C group was higher than that of group 37°C, 33°C, and 28°C (35°C vs. 37°C and 28°C, $p<0.01$ , 35°C vs. 33°C, $p<0.05$ ). Group 35°C and 33°C resulted in longer survival ( $p<0.01$ ), higher survival rate ( $p<0.01$ ), and lower NDS (35°C vs. 37°C and 28°C, $p<0.01$ , 33°C vs. 37°C and 28°C, $p<0.05$ ) compared with the group 37°C and 28°C. The extent of damage to cerebral cortex cells in group of 35°C and 33°C was lighter than that in group of 37°C and 28°C. The 35°C group spent less time in the process of cooling and rewarming than the group 33°C and 28°C ( $p<0.01$ ). Conclusions. An almost equal protective effect of milder hypothermia (35°C) and mild hypothermia (33°C) in cardiac arrest (CA) rats was achieved with more predominant effect than moderate hypothermia (28°C) and normothermia (37°C). More importantly, shorter time spent in cooling and rewarming was required in the 35°C group, indicating its potential clinical application. These findings support the possible use of milder hypothermia (35°C) as a therapeutic agent for postresuscitation.