title: A comparison of alpha-methylnorepinephrine, vasopressin and epinephrine for cardiac resuscitation.
abstract: The objective of this research was to compare the effects of an alpha- and beta-adrenergic agonist, epinephrine, a selective alpha(2)-adrenergic agonist, alpha-methylnorepinephrine (alpha-MNE), and a non-adrenergic vasopressin on post-resuscitation myocardial function and duration of survival. Epinephrine continues to be the primary adrenergic agent for advanced cardiac life support. However, its major inotropic actions and especially its beta-adrenergic and, to a lesser extent, its alpha(1)-actions increase the severity of global ischemia during cardiac arrest and adversely affect post-resuscitation myocardial function and survival. We had previously observed significantly better outcomes with a selective alpha(2)-adrenergic agonist when compared with epinephrine. Non-adrenergic vasopressin also has promise of more favorable actions. The present study was, therefore, undertaken to compare a selective alpha(2)-adrenergic vasopressor drug with vasopressin, epinephrine, and saline placebo. Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. Mechanical ventilation and precordial compression were initiated after 8 min of untreated VF. About 2 min later, alpha-MNE in a dose of 100 microgram/kg, vasopressin in a dose of 0.4 U/kg, epinephrine in a dose of 30 microgram/kg, or saline control was administered. Defibrillation was attempted after 6 min of CPR. Left ventricular pressure, dP/dt(40), -dP/dt, and cardiac index were measured for an interval of 240 min after resuscitation. Except for saline controls, comparable increases in coronary perfusion pressure (CPP) were observed after each drug intervention. All animals were successfully resuscitated. Post-resuscitation myocardial function and survival were significantly better in animals treated with alpha-MNE. Both post-resuscitation myocardial function and survival were most improved after administration of the selective alpha(2)-adrenergic agonist, intermediate after vasopressin and least after epinephrine and saline placebo.
authors.affiliation: The Institute of Critical Care Medicine, 1695 North Sunrise Way, Bldg. # 3, 92262-5309, Palm Springs, CA, USA.
authors.forename: Kada
authors.initials: K
authors.lastname: Klouche
authors.forename: Max Harry
authors.initials: MH
authors.lastname: Weil
authors.forename: Shijie
authors.initials: S
authors.lastname: Sun
authors.forename: Wanchun
authors.initials: W
authors.lastname: Tang
authors.forename: Dan Hong
authors.initials: DH
authors.lastname: Zhao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002302:Cardiac Output / Q000502:physiology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D008771:Nordefrin / Q000494:pharmacology*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000401:mortality / Q000628:therapy*
chemical_list: D014662:Vasoconstrictor Agents; D014667:Vasopressins; D008771:Nordefrin