Alpha-methylnorepinephrine, a selective alpha2-adrenergic agonist for cardiac resuscitation

OBJECTIVES The purpose of this study was to investigate the effects of a selective alpha(2)-adrenergic agonist, alpha-methylnorepinephrine (alphaMNE) as an alternative vasopressor agent during cardiopulmonary resuscitation (CPR). BACKGROUND For more than 40 years, epinephrine has been the vasopressor agent of choice for CPR. Its beta- and alpha(1)-adrenergic effects increase myocardial oxygen consumption, magnify global myocardial ischemia and increase the severity of postresuscitation myocardial dysfunction. METHODS Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. After 8 min of untreated VF, mechanical ventilation and precordial compression began. AlphaMNE, epinephrine or saline placebo was injected into the right atrium 2 min after the start of precordial compression. As an additional control, one group of animals was pretreated with alpha, receptor blocker, yohimbine, before injection of alphaMNE. Defibrillation was attempted 4 min later. Left ventricular pressure, dP/dt(40) negative dP/dt and cardiac index were measured for an interval of 240 min after resuscitation. RESULTS Except for saline placebo and yohimbine-treated animals, comparable increases in coronary perfusion pressure were observed after each drug intervention. All animals were successfully resuscitated. Left ventricular diastolic pressure, cardiac index, dP/dt,, and negative dP/dt were more optimal after alphaMNE; this was associated with significantly better postresuscitation survival. Pretreatment with yohimbine abolished the beneficial effects of alphaMNE. CONCLUSIONS The selective alpha(2)-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival. (J Am Coil Cardiol 2001;37:951-6) (C) 2001 by the American College of Cardiology.