Fengqing Song

The effects of epinephrine on outcomes of normothermic and therapeutic hypothermic cardiopulmonary resuscitation

Objective:To investigate the effects of epinephrine when administered during either normothermic or therapeutic hypothermic cardiopulmonary resuscitation on postresuscitation myocardial and cerebral function and survival. Design:Prospective, randomized, placebo-controlled experimental study. Setting:University-affiliated animal research laboratory. Subjects:Thirty-two healthy male Sprague-Dawley rats. Interventions:Ventricular fibrillation was induced and untreated for 8 mins. The animals were then randomly assigned to one of four groups: normothermic placebo control; normothermic epinephrine; hypothermic placebo control; and hypothermic epinephrine. Hypothermia was initiated coincident with the start of cardiopulmonary resuscitation. The blood temperature was reduced and maintained at 32 ± 0.2°C and continued for 4 hrs after resuscitation. Normothermic animals were maintained at 37 ± 0.2°C. Either placebo or epinephrine (20 &mgr;g/kg) was administered 5 mins after the start of cardiopulmonary resuscitation and 3 mins before defibrillation. Measurements and Main Results:Postresuscitation cardiac output, ejection fraction, and myocardial performance index were measured hourly for 4 hrs after resuscitation; neurologic deficit scores were measured daily for 7 days, and durations of survival were observed for up to 3 mos. Except for three normothermic control animals, all animals were resuscitated. When epinephrine was administered during normothermic cardiopulmonary resuscitation, postresuscitation myocardial function was severely impaired when compared with the normothermic control group. However, postresuscitation myocardial function was significantly better in animals treated with epinephrine during hypothermic cardiopulmonary resuscitation when compared with hypothermic controls. This was associated with significantly fewer postresuscitation ventricular arrhythmias, less ST-segment elevation, better postresuscitation neurologic deficit scores, and longer duration of survival. Conclusions:Epinephrine, when administered during normothermic cardiopulmonary resuscitation, significantly increases the severity of postresuscitation myocardial dysfunction and decreases the duration of survival. These detrimental effects of epinephrine, however, no longer exist when it is administered during therapeutic hypothermic cardiopulmonary resuscitation.

Pharmacologically induced hypothermia with cannabinoid receptor agonist WIN55, 212-2 after cardiopulmonary resuscitation*

Objective:To investigate whether hypothermia could be induced pharmacologically after resuscitation with the cannabinoid CB1/CB2 receptor agonist in a rat model and its effects on outcomes of cardiopulmonary resuscitation. Design:Prospective, randomized, placebo-controlled experimental study. Setting:University-affiliated animal research laboratory. Subjects:Ten healthy male Sprague-Dawley rats. Interventions:Ventricular fibrillation was induced and untreated for 6 mins. Defibrillation was attempted after 8 mins of cardiopulmonary resuscitation. Thirty minutes after resuscitation, animals were randomized to receive either WIN55, 212-2 (1.0 mg/kg/hr) or vehicle placebo (1.4 mL/kg/hr) for 6 hrs. Before infusion, the temperature was maintained at 37°C in all the animals with the help of a heating lamp. The same temperature environment was maintained for both groups after infusion. Measurements and Main Results:Hemodynamic measurements and cardiac output, ejection fraction, and myocardial performance index were measured at baseline and hourly for 6 hrs after resuscitation. Survival time up to 72 hrs was observed. Results:Blood temperature decreased progressively after infusion of WIN55, 212-2 from 37°C to 34°C 4 hrs after resuscitation. There was no significant change in blood temperature after 6 hrs of placebo infusion of the same volume and same infusate temperature. Significantly better postresuscitation myocardial function and longer durations of survival were observed in WIN55, 212-2-treated animals. Conclusions:The selective cannabinoid agonist, WIN55, 212-2, produced a significant reduction in blood temperature and improved postresuscitation myocardial functions and survival after cardiopulmonary resuscitation. The study results may provide a further option for early and effective induction of therapeutic hypothermia in settings of cardiopulmonary resuscitation.

Cholecystokinin octapeptide induces hypothermia and improves outcomes in a rat model of cardiopulmonary resuscitation.

Objectives:To investigate the effects of cholecystokinin octapeptide on thermoregulation, postresuscitation myocardial function, neurologic outcome, and duration of survival in a rat model of cardiopulmonary resuscitation. Design:Prospective, randomized, placebo-controlled experimental study. Setting:University-affiliated animal research laboratory. Subjects:Ten male Sprague-Dawley rats. Interventions:Ventricular fibrillation was induced and untreated for 6 mins. Defibrillation was attempted after 8 mins of cardiopulmonary resuscitation. Animal temperature was adjusted to 37.0°C with the aid of a heating lamp. At 30 mins after resuscitation, animals were randomized to receive an intravenous injection of either cholecystokinin octapeptide (200 &mgr;g/kg in 0.3 mL saline) or vehicle placebo (0.3 mL saline). The ambient temperature settings and that of the distance of the heating lamp from the animal remained the same in both groups throughout the entire experiment. Measurements and Main Results:Body temperature, hemodynamic measurements, and postresuscitation myocardial function, including cardiac output, left ventricular ejection fraction, and myocardial performance index, were measured together with neurologic deficit scores and duration of survival. Results:After injection of cholecystokinin octapeptide, blood temperature decreased progressively from 37.0°C to 34.8°C 5 hrs after resuscitation and returned to 37.0°C at 9 hrs after injection. In the control group, blood temperature was sustained at 37.0°C ± 0.2°C during the same period of observation. Myocardial and neurologic function and duration of survival were significantly better in the cholecystokinin octapeptide-treated animals when compared to the control group. Conclusions:In a rat model of cardiopulmonary resuscitation, cholecystokinin octapeptide induced mild hypothermia, attenuated postresuscitation myocardial dysfunction, and improved neurologic outcome and duration of survival.

Apoptosis is not involved in the mechanism of myocardial dysfunction after resuscitation in a rat model of cardiac arrest and cardiopulmonary resuscitation.

Objective:To investigate the presence of apoptosis after the global myocardial ischemia of cardiopulmonary resuscitation and the regional myocardial ischemia after left anterior descending coronary artery occlusion and relate it to the severity of postresuscitation myocardial dysfunction. Design:Prospective animal study. Setting:University-affiliated animal research laboratory. Subjects:Male Sprague-Dawley rats. Interventions:Fifteen male Sprague-Dawley rats weighing 450–550 g were randomized to: (1) 8 mins of untreated cardiac arrest followed by 6 mins of cardiopulmonary resuscitation; (2) left anterior descending coronary artery occlusion for 45 mins followed by 4 hrs of reperfusion; and (3) left anterior descending coronary artery sham group. Cardiac functions, including ejection fraction, analog differentiation of left ventricular pressure at 40 mm Hg, and rate of maximal left ventricular pressure decline were continuously measured for 4 hrs. The hearts were then harvested for the terminal transferase-mediated 2′-deoxyuridine, 5′-triphosphate nick end-labeling assay analysis. Measurements and Main Results:Myocardial function was significantly impaired after resuscitation from cardiac arrest and reperfusion from left anterior descending coronary artery occlusion (p < .01). There was no difference in the percentage of apoptotic cells between the cardiopulmonary resuscitation animals and sham-operated animals. Fewer apoptotic cells were observed in cardiac arrest/cardiopulmonary resuscitation animals in comparison to left anterior descending coronary artery occlusion animals (p < .05), even though myocardial function was more severely impaired after resuscitation (p < .01). Conclusions:Myocardial function was significantly impaired after cardiac arrest/cardiopulmonary resuscitation and ischemia/reperfusion. However, apoptosis was not involved in the mechanism of postresuscitation myocardial dysfunction in this setting.

Effect of therapeutic hypothermia vs δ-opioid receptor agonist on post resuscitation myocardial function in a rat model of CPR

AIM This study is to compare the effect of the δ-opioid receptor agonist, D-Ala(2)-D-Leu(5) enkephalin (DADLE) with normothermic control and therapeutic hypothermia on post resuscitation myocardial function and 72-h survival in a rat model of cardiac arrest and resuscitation. METHODS Ventricular fibrillation (VF) was induced in 15 male Sprague-Dawley rats. After 8 min of untreated VF, cardiopulmonary resuscitation was performed for 8 min before defibrillation. Animals were randomized to three groups of five: (a) normothermia; (b) hypothermia (32 °C); and (c) normothermia with DADLE intravenous infusion (1 mg/kg h(-1)). Hypothermia and drug infusion were started after successful defibrillation. Myocardial functions, including cardiac output (CO), left ventricular ejection fraction (LVEF), and myocardial performance index (MPI) were measured echocardiographically together with duration of survival. RESULTS The 72-h survival was significantly greater in the hypothermic group than in both DADLE and normothermic group (p = 0.02). However, the survival time of the DADLE treated animals was significantly longer than that of the normothermia group (51.8 ± 18.9 vs 18.8 ± 10.1h, p < 0.01). DADLE group showed significantly better CO (PR 60 min, p = 0.049), better LVEF (PR 60 min, p = 0.044; PR 240 min, p < 0.001) and lower MPI (PR 60 min, p = 0.043; PR 240 min, p = 0.045) than normothermic group. Hypothermia group also showed significantly better CO (PR 60m in, p = 0.044; PR 240 min, p = 0.007), better LVEF (PR 60 min, p = 0.001; PR 240 min, p < 0.001) and lower MPI (PR 60 min, p = 0.003; PR 240 min, p = 0.012) than the normothermic group. CONCLUSIONS DADLE attenuated post resuscitation myocardial dysfunction and increased short term survival time. However, the 72-h survival in the DADLE group was less than that in the hypothermia group.