title: A selective alpha(2)-adrenergic agonist for cardiac resuscitation.
abstract: The effects of selective alpha(2)-adrenergic agonist alpha-methylnorepinephrine on the initial success of resuscitation and postresuscitation myocardial function were compared with nonselective alpha- and beta-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 alpha(2)-adrenergic agonist, alpha-methylnorepinephrine (alpha-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 alpha-MNE (100 microg/kg) or epinephrine (20 microg/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 alpha-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 alpha-MNE, respectively, after resuscitation. Epinephrine and alpha-MNE increased postresuscitation heart rate by 38% and 15%, respectively. Accordingly, significantly less postresuscitation impairment followed the administration of alpha-MNE. alpha-MNE, a selective alpha-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.
authors.affiliation: Institute of Critical Care Medicine, Palm Springs, CA 92262-5309, USA. weilm@911research.com
authors.forename: Kada
authors.initials: K
authors.lastname: Klouche
authors.forename: Max Harry
authors.initials: MH
authors.lastname: Weil
authors.forename: Wanchun
authors.initials: W
authors.lastname: Tang
authors.forename: Heitor
authors.initials: H
authors.lastname: Povoas
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamohara
authors.forename: Joe
authors.initials: J
authors.lastname: Bisera
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004837:Epinephrine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D023421:Models, Animal; D008771:Nordefrin / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D014662:Vasoconstrictor Agents
chemical_list: D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D008771:Nordefrin; D004837:Epinephrine