A selective α2-adrenergic agonist for cardiac resuscitation

Abstract

The effects of selective α2-adrenergic agonist α-methylnorepinephrine on the initial success of resuscitation and postresuscitation myocardial function were compared with nonselective α- and β-adrenergic epinephrine in a swine model of cardiac arrest. Epinephrine, the primary pharmacological intervention in the treatment of cardiac arrest, improves immediate outcome. However, epinephrine increases the severity of myocardial dysfunction after cardiac resuscitation. Both inotropic and chronotropic actions provoke disproportionate increases in myocardial oxygen consumption by the ischemic heart, prompting this study, in which we hypothesized that a selective α2-adrenergic agonist, α-methylnorepinephrine (α-MNE), would moderate these adverse effects of epinephrine and minimize postresuscitation myocardial dysfunction. After 7 minutes of untreated ventricular fibrillation (VF) in 14 anesthetized male domestic pigs, precordial compression at a fixed rate of 80 compressions/min was begun, along with mechanical ventilation. Either α-MNE (100 μg/kg) or epinephrine (20 μg/kg) was administered as a bolus after 2 minutes of precordial compression. After an additional 4 minutes of precordial compression, defibrillation was attempted. Left ventricular systolic and diastolic function was quantitated with the use of transesophageal echo-Doppler imaging. Comparable increases in coronary perfusion pressure to 15 mm Hg were observed after the administration of both drugs. All animals were successfully resuscitated; epinephrine and α-MNE were equally quick in restoring spontaneous circulation after 7 minutes of untreated VF. Ejection fraction was reduced by 35% and 14% by epinephrine and α-MNE, respectively, after resuscitation. Epinephrine and α-MNE increased postresuscitation heart rate by 38% and 15%, respectively. Accordingly, significantly less postresuscitation impairment followed the administration of α-MNE. α-MNE, a selective α-adrenergic agonist, was as effective as epinephrine in restoring spontaneous circulation after 7 minutes of untreated VF in a porcine model for CPR and demonstrated lesser postresuscitation myocardial injury. (J Lab Clin Med 2002;140:27-34)