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EXPERIMENTAL STUDY

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

Shijie Sun, MD^* , Max Harry Weil, MD, PhD, FACC^* , Wanchun Tang, MD^* , Takashi Kamohara, MD^* and Kada Klouche, MD^*

^* Institute of Critical Care Medicine, Palm Springs, California, USA
Keck School of Medicine of the University of Southern California, Los Angeles, California, USA

Manuscript received July 17, 2000; revised manuscript received October 16, 2000, accepted November 17, 2000.

Reprint requests and correspondence: Dr. Max Harry Weil, The Institute of Critical Care Medicine, 1695 North Sunrise Way, Building #3, Palm Springs, California 92262-5309
weilm{at}aol.com

OBJECTIVES

The purpose of this study was to investigate the effects of a selective alpha₂-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 alpha₁-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 alpha₂-receptor blocker, yohimbine, before injection of alphaMNE. Defibrillation was attempted 4 min later. Left ventricular pressure, dP/dt₄₀, 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/dt₄₀ 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 alpha₂-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.

Abbreviations and Acronyms   alphaMNE = alpha-methylnorepinephrine   CPR = cardiopulmonary resuscitation   dP/dt40 = measured at an intraventricular pressure of 40 mm Hg   FiO2 = inspired oxygen fraction   PCO2 = blood carbon dioxide tension   PETCO2 = end tidal PCO2   VF = ventricular fibrillation

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