An Experimental Circulatory Arrest Model in the Rat to Evaluate Calcium Antagonists in Cerebral Resuscitation

A circulatory arrest model in the rat was developed for use in cerebral and cardiac resuscitation studies. Whole-body ischemia was produced for 8 to 18 minutes by arresting the heart with a cold potassium chloride cardioplegic solution. Following cardiopulmonary resuscitation, minimal, standardized intensive care was provided. As the duration of ischemia was increased from 8 to 18 minutes, survival immediately following resuscitation decreased from 100% to 25%, and survival at 48 hours after ischemia decreased from 80% to 0%. Thirty per cent of the rats recovering from 11 minutes of ischemia suffered motor seizures. Survival and the incidence of motor seizures appear to be good measures of outcome following ischemic circulatory arrest. These measures can be used to test the possible anti-ischemic actions of calcium antagonists or other drugs

Protection of Ischemic Myocardium by Whole-Body Hypothermia After Coronary Artery Occlusion in Dogs

Anesthetized dogs were cooled to a core body temperature of 26°C or maintained at a body temperature of 37°C during periods of 5 and 10 hours of LAD coronary artery occlusion. Subsequent macroscopic dehydrogenase enzyme mapping showed that ischemic injury was 25 per cent less after 5 hours of coronary occlusion and 20 per cent less after 10 hours of occlusion in hypothermic dogs than in normothermic controls. The heart rate and left ventricular minute work in hypothermic dogs decreased to roughly half the levels measured in normothermic animals, while left ventricular contractility was 10 to 40 per cent lower in hypothermic dogs than in normothermic dogs. However, cardiac index and left ventricular end-diastolic pressure were unchanged by whole body cooling. Thus, hypothermia appeared to diminish the oxygen requirements of the ischemic myocardium without reducing the performance of the heart as a pump. Hypothermia may be useful as a therapeutic adjunct to myocardial revascularization or pharmacologrc interventions

Endotracheal Versus Intravenous Epinephrine During Electromechanical Dissociation with CPR in Dogs

The dose-response curves of epinephrine given either IV or endotracheally (ET) were compared during resuscitation from electromechanical dissociation (EMD). Ten anesthetized dogs were subjected to a two-minute period of electrically induced ventricular fibrillation (VF) followed by defibrillation without CPR to produce EMD. Mechanical CPR was followed by injection of either ET or IV epinephrine. Successful response was defined as a return of pulsatile blood pressure within two minutes of drug administration. Using log-dose increments of epinephrine, experimental trials were repeated in each animal. The IV and ET median effective doses were 14 and 130 g/kg, respectively. When the trials were successful, the time between drug administration and either arterial blood pressure increases or return of spontaneous circulation did not differ significantly for the ET and IV groups. These results show that the dosage for epinephrine delivered ET must be higher than the IV dosage to achieve the same response during CPR

Therapeutic indices for transchest defibrillator shocks: Effective, damaging, and lethal electrical doses

Although prospective studies of defibrillator shock overdose cannot be performed in man, the therapeutic indices of various defibrillating current waveforms can be measured in animals. We determined the ratios TD50/ED50 and LD50/ ED50 (where TD50 = median toxic or damageinducing dose, ED50 = median effective or defibrillating dose, and LD50 = median lethal dose) as measures of the therapeutic index for damped sine wave defibrillator shocks in dogs. Death of an animal and/or any degree of cardiac damage found by gross or microscopic examination were defined as harmful effects of shock, analogous to drug toxicity. In terms of peak current, the ED50, TD50, and LD50 were 1.1, 5.8, and 24 amperes/ kg; the therapeutic indices were TD50/ED50 = 5 for morphologic damage and LD50/ED50 = 22 for death. In terms of delivered energy the ED50, TD50, and LD50 were 1.5, 30, and 470 joules/kg; the therapeutic indices were TD50/ED50 = 20 for damage and LD50/ED50 = 320 for death. These data indicate a reasonable margin of safety for damped sine wave defibrillator shocks in dogs, and are consistent with reported incidences of suspected shockinduced damage in humans

Myocardial Perfusion Pressure: A Predictor of 24Hour Survival During Prolonged Cardiac Arrest in Dogs

Myocardial perfusion pressure, defined as the aortic diastolic pressure minus the right atria1 diastolic pressure, correlates with coronary blood flow during cardiopulmonary resuscitation (CPR) and predicts initial resuscitation success. Whether this hemodynamic parameter can predict 24-h survival is not known. We examined the relationship between myocardial perfusion pressure and 24-h survival in 60 dogs that underwent prolonged (20 min) ventricular fibrillation and CPR. Forty-two (70%) animals were initially resuscitated and 20 (33%) survived for 24 h. Myocardial perfusion pressure was significantly greater when measured at 5, 10, 15 and 20 min of ventricular fibrillation in the resuscitated animals than in the non-resuscitated animals (P \u3c 0.01). Likewise, the myocardial perfusion pressure was also greater in the animals that survived 24 h than in animals that were resuscitated, but died before 24 h (P \u3c 0.02). Myocardial perfusion pressure measured after 10 min of CPR was 11 2 mmHg in animals never resuscitated, 20 3 mmHg in those resuscitated that died before 24 h and 29 2 mmHg in those that survived 24 h (P \u3c 0.05). A myocardial perfusion pressure at 10 min of CPR of 20 mmHg or less is an excellent predictor of poor survival (negative predictive value = 96%). Myocardial perfusion pressure is a useful index of CPR effectiveness and therefore may be a useful guide in helping to optimize resuscitation efforts

Changes in Expired End-Tidal Carbon Dioxide During Cardiopulmonary Resuscitation in Dogs: A Prognostic Guide for Resuscitation Efforts

Expired end-tidal carbon dioxide (PCO2) measurements made during cardiopulmonary resuscitation have correlated with cardiac output and coronary perfusion pressure when wide ranges of blood flow are included. The utility of such measurements for predicting resuscitation outcome during the low flow state associated with closed chest cardiopulmonary resuscitation remains uncertain. Expired end-tidal PCO2 and coronary perfusion pressures were measured in 15 mongrel dogs undergoing 15 min of closed chest cardiopulmonary resuscitation after a 3 min period of untreated ventricular fibrillation. In six successfully resuscitated dogs, the mean expired end-tidal PCO2 was significantly higher than that in nine nonresuscitated dogs only after 14 min of cardiopulmonary resuscitation (6.2 ± 1.2 versus 3.4 ± 0.8 mmHg; p \u3c 0.05). No differences in expired end-tidal PCO2 values were found at 2, 7 or 12 min of cardiopulmonary resuscitation. A significant decline in end-tidal PCO2 levels during the resuscitation effort was seen in the nonresuscitated group (from 6.3 ± 0.8 to 3.4 ± 0.8 mmHg; p \u3c 0.05); while the successfully resuscitated group had constant PCO2 levels throughout the 15 min of cardiac arrest (ranging from 6.8 ± 1.1 to 6.2 ± 1.2 mmHg). Changes in expired PCO2 levels during cardiopulmonary resuscitation may be a useful noninvasive predictor of successful resuscitation and survival from cardiac arrest