Intra-Arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model

Abstract

Background-Recent clinical studies have demonstrated that hypothermia to 32°to 34°C provides significant clinical benefit when induced after resuscitation from cardiac arrest. However, cooling during the postresuscitation period was slow, requiring 4 to 8 hours to achieve target temperatures after return of spontaneous circulation (ROSC). Whether more rapid cooling would further improve survival remains unclear. We sought to determine whether cooling during cardiac arrest before ROSC (ie, "intra-arrest" hypothermia) has survival benefit over more delayed post-ROSC cooling, using a murine cardiac arrest model. Methods and Results-A model of potassium-induced cardiac arrest was established in C57BL/6 mice. After 8 minutes of untreated cardiac arrest, resuscitation was attempted with chest compression, ventilation, and intravenous fluid. Mice were randomized to 3 treatment groups (nϭ10 each): an intra-arrest hypothermia group, in which mice were cooled to 30°C just before attempted resuscitation, and then rewarmed after 1 hour; a post-ROSC hypothermia group, in which mice were kept at 37°C for 20 minutes after successful ROSC and then were cooled to 30°C for 1 hour; and a normothermic control group, in which mice were kept at 37°C. The intra-arrest hypothermia group demonstrated better 72-hour survival than delayed hypothermia and normothermia groups (6/10 versus 1/10 and 1/10 survivors, respectively, PϽ0.05), with similar differences seen at 6-hour survival and on neurological scoring. Conclusions-Timing of hypothermia is a crucial determinant of survival in the murine arrest model. Early intra-arrest cooling appears to be significantly better than delayed post-ROSC cooling or normothermic resuscitation. (Circulation.

Combination of Intravenous Ascorbic Acid Administration and Hypothermia After Resuscitation Improves Myocardial Function and Survival in a Ventricular Fibrillation Cardiac Arrest Model in the Rat

“…The neurologic outcomes of the studied animals were evaluated with neurologic function scoring at the sixth, 24th, 48th, and 72nd hours following ROSC (Table 1). 19 Assessments were performed independently by two investigators. Any discrepancies were resolved by an independent assessment by a third investigator, and the score chosen by the majority was accepted.…”

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

“…However, the optimal timing and duration of hypothermia after arrest with respect to reperfusion remains unclear, with the suggestion that "sooner is better" in terms of cooling onset relative to reperfusion (31a). Indeed, cooling in our mouse model of cardiac arrest is highly protective against cardiac and neurological injury when induced during ischemia (i.e., during cardiac arrest) and maintained for 1 h after reperfusion (i.e., ROSC) (1). Delaying hypothermia by even minutes into reperfusion after cardiac arrest abrogates protection (1).…”

How Can we Study Cardiopulmonary Resuscitation and Cardiac Arrest in Animals: a Review

“…The intravenous administration of potassium chloride was also shown to induce a very reproducible cardiac arrest in rodents [9,13,14]. It leads to a quasi-immediate cardiac arrest with asystole.…”

“…On the other hand, spontaneous heart rate is much higher in rodents than in large animals and humans as usual values average 260-450 or 500-600 beats per minute in awake rats and mice, respectively [7,8]. This directly impacts the required chest compression rate in those species as mice should undergo ≈400 compressions per min to be resuscitated [9][10][11][12][13][14]. Magnetic resonance imaging also showed that usual ejection fraction are higher in mice as compared to humans (75% vs 55%) [15].…”

“…In survivors, neurological function is typically assessed using clinical deficit scores with specific grids for each species. They are based on the clinical evaluation of consciousness, behavior, breathing, reflexes, and locomotion tests [9,[11][12][13][28][29][30][31]41,50,53]. Neurological recovery can be further assessed with quantitative behavioral tests in rodents, such as the T maze or the Morris maze test [59][60][61].…”