ADRENERGIC AGENTS FOR CARDIOPULMONARY RESUSCITATION

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DESCRIPTION (adapted from the applicant's abstract): The applicant states that until recently, cardiopulmonary resuscitation (CPR) research has focused primarily on the initial stage of cardiac resuscitation (Stage 1) and therapeutic options by which a viable rhythm and spontaneous circulation are restored. However, the applicant indicates that both clinical and experimental observations indicate substantial impairment of cardiac work capability after resuscitation from cardiac arrest (Stage 2); this may explain, at least in part, the fatal outcome of more than one-half of patients in the early hours and days following the initial success of CPR. This application is for support of pre-clinical studies on the combined effects of adrenergic drugs and buffer agents on post-resuscitation myocardial function and 72 hour survival. The goal is to define the rationale for and optimization of pharmacological support such that not only immediate resuscitation but also post-resuscitation ventricular function, survival, and neurological outcome are improved. The adrenergic agent to be used is epinephrine after its beta1-adrenergic actions have been blocked by esmolol. The buffer agents will include a CO2 generating buffer agent (sodium bicarbonate) and a CO2 consuming organic buffer (tromethamine). Controlled experiments on the effects of each of these agents separately on post-resuscitation myocardial function and survival are proposed. The applicant proposes to extend studies such as to expose the combined effects of adrenergic and buffer agents. An established and standardized rodent model will be utilized. Ventricular fibrillation will be induced and resuscitation attempted with electrical defibrillation after an interval of either 12 or 15 minutes of untreated cardiac arrest and an additional 12 min of "conventional" CPR. Post-resuscitation myocardial function, neurological recovery and duration of survival will be compared. Post-resuscitation myocardial function will be compared based on measurements of cardiac output with computation of left ventricular stroke work, aortic and right atrial pressure with computation of coronary perfusion pressure, left ventricular systolic and diastolic pressures, dP/dt40, negative dP/dt, and negative dP/dt50.