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(Circulation. 2004;109:2469-2474.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Short-Acting ß-Adrenergic Antagonist Esmolol Given at Reperfusion Improves Survival After Prolonged Ventricular Fibrillation

Cheryl R. Killingsworth, DVM, PhD; Chih-Chang Wei, PhD; Louis J. Dell’Italia, MD; Jeffrey L. Ardell, PhD; Melody A. Kingsley; William M. Smith, PhD; Raymond E. Ideker, MD, PhD; Gregory P. Walcott, MD

From the Cardiac Rhythm Management Laboratory, Division of Cardiovascular Diseases, Departments of Medicine (C.R.K., C.-C.W., L.J.D., M.A.K., R.E.I., G.P.W.), Biomedical Engineering (W.M.S., R.E.I.), Veterans Affairs (L.J.D.), and Physiology (R.E.I., L.J.D.), University of Alabama at Birmingham, and the Department of Pharmacology (J.L.A.), East Tennessee State University, Johnson City.

Correspondence to Cheryl R. Killingsworth, DVM, PhD, Cardiac Rhythm Management Laboratory, 1670 University Blvd, B140 Volker Hall, Birmingham, AL 35294-0019. E-mail crk{at}crml.uab.edu

Received November 18, 2003; revision received February 3, 2004; accepted February 6, 2004.

Background— High catecholamine concentrations are cytotoxic to cardiac myocytes. We hypothesized that myocardial interstitial catecholamine levels are greatly elevated immediately after long-duration ventricular fibrillation (VF), defibrillation, and reperfusion and that the short-acting ß-antagonist esmolol administered at reperfusion would protect against this catecholamine surge and improve survival.

Methods and Results— In part 1 of this study, catecholamines from myocardial interstitial fluid (ISF) and aortic and coronary sinus plasma were quantified by use of ³H-labeled radioenzymatic assay in 8 open-chest, anesthetized pigs. Eight minutes of electrically induced VF was followed by internal defibrillation and reperfusion. By 4 minutes of VF, ISF norepinephrine increased significantly, from 1.3±0.3 to 7.4±2.4 ng/mL. Epinephrine increased significantly, from 0.4±0.2 to 1.5±0.7 ng/mL. ISF norepinephrine and epinephrine peaked at 219.2±92.1 and 63.7±25.1 ng/mL after defibrillation and reperfusion and decreased significantly to 12.2±3.5 and 6.7±3.1 ng/mL 23 minutes after defibrillation. Transcardiac catecholamine changes were similar. In part 2, 8 minutes of VF was followed by external defibrillation in anesthetized, closed-chest pigs. Animals received 1.0 mg/kg esmolol (n=8) or saline (n=8) intravenously at the start of cardiopulmonary resuscitation (CPR). Advanced cardiac life support, including CPR and epinephrine, was delivered to both groups. Esmolol before reperfusion improved return of spontaneous circulation and 4-hour survival (7/8 versus 3/8 survivors, ² P<0.05).

Conclusions— Transcardiac and ISF norepinephrine and epinephrine levels are briefly massively elevated after 8 minutes of VF, defibrillation, and reperfusion. A short-acting ß-antagonist administered immediately after defibrillation improves return of spontaneous circulation and 4-hour survival after this prolonged VF.

Key Words: catecholamines • cardiopulmonary resuscitation • norepinephrine • defibrillation

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