Once initial defibrillation has failed, the advanced cardiac life support (ACLS) guidelines for cardiopulmonary resuscitation (CPR) recommend periodic intravenous administration of epinephrine to increase coronary artery perfusion pressure (CPP) via arterial vasoconstriction to [1]. During prolonged cardiac arrest coronary perfusion pressure and forward blood flow are the major determinants of successful resuscitation, for when CPP is too low, successful resuscitation is unlikely. When the CPP is marginal, resuscitation may be possible; however, 24-h survival is unlikely [2]. When CPR is able to generate CPP above 30 mmHg associated with adequate forward blood flow as reflected in an adequate end-tidal CO2 the 24-h survival rate is greatly improved [2]. The American Heart Association ACLS guidelines recommend epinephrine as the pressor agent of choice during prolonged CPR [1]. These recommendations are based on now classic works [2–8]. Yet, studies have accumulated over the years that have raised concern that epinephrine’s beta-adrenergic effect may increase the myocardial oxygen consumption of the fibrillating heart and predispose to post-defibrillation dysfunction and cardiac arrhythmias [9–16]. Added to this concern was the finding that endogenous catecholamine concentrations are high during ventricular fibrillation even in the absence of epinephrine administration [11]. Ditchey and associates found, in a canine ventricular fibrillation cardiac arrest model, that the balance between myocardial oxygen supply and demand was improved by the administration of propranolol and phenylephrine, an exogenous selective alpha-agonist [9]. The limitations of these studies, however, is that high-dose epinephrine was used and survival was not evaluated. High-dose epinephrine administered during resuscitation initially appeared to be useful, producing higher perfusion pressures, but high-dose epinephrine has not been shown in clinical trials [17,18] nor in some experimental trials [12,13] to improve survival. Studies from our laboratory found that high-dose epinephrine resulted in postresuscitative tachycardia, systemic hypertension and greater early mortality relative to the standard dose [12]. Other laboratories have also documented adverse effects of high-dose epinephrine when given during CPR, including post-resuscitation hyperadrenergic state [14], myocardial necrosis [15], and worsened post-arrest cardiomyopathy [16]. Although pure alpha-agonists have not been shown to be superior to epinephrine [19–22], one could speculate that a combination of an alpha-adrenergic agonist and a beta-blocker might improve hemodynamics during CPR and thus improve long-term survival while avoiding the post resuscitation problem of excessive beta stimulation. * Correspnding author. Tel.: +1-520-626-7383.