Abstract 292: Comparison of Pharmacological and Physical Hypothermia in Cerebral and Myocardial Function in a Porcine Model of Cardiac Arrest and Resuscitation

Abstract

Objective: Non-selective cannabinoid (CB) 1/2 receptor agonist, WIN 55,212-2, has been demonstrated to produce pharmacological hypothermia and improved outcomes of CPR in a rat model. In this study, we compared the effects of pharmacological hypothermia induced by WIN 55,212-2 and physical hypothermia by surface cooling in myocardial and neurological function in a porcine model of CPR. Hypothesis: Pharmacological hypothermia by WIN 55,212-2 produced the similar or better cerebral and myocardial function as surface cooling. Methods and results:Ventricular fibrillation (VF) was induced in 14 male domestic pigs weighing between 35 ± 2 kg. CPR was initiated after 7 min of untreated VF. Defibrillation was attempted after 5 min of CPR. If ROSC was not achieved, two mins of CPR was continued and sequenced with defibrillation attempt until ROSC or for a total of 15 mins. At 5 min post resuscitation, animals are randomized to receive intravenous infusion with WIN 55,212-2 at a dose of 1.0 mg/kg/h or surface cooling until blood temperature cooled down to 34 celcius degree and maintained for 4 hrs. When compared to the animals treated with surface cooling, significantly improvement in neurological alertness score (NAS) was observed in the WIN 55,212-2 treated animals at 24 and 48 hrs, but not at 72 hrs (WIN 55,212-2 vs surface cooling: 24 hrs, 93 ± 5 vs 77 ± 12, p<0.01; 48 hrs, 100 ± 0 vs 93 ± 6, p=0.01) (Figure 1A). As to the post resuscitation myocardial function, there was no significant difference in ejection fraction (EF) between these two groups (Figure 1B). Conclusions: Pharmacological hypothermia induced by WIN 55,212-2 exerted better post resuscitation short-term neurological function than physical hypothermia with the similar post resuscitation myocardial function.