title: Short-acting beta-adrenergic antagonist esmolol given at reperfusion improves survival after prolonged ventricular fibrillation.
abstract: 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 beta-antagonist esmolol administered at reperfusion would protect against this catecholamine surge and improve survival.
  
  
  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, chi2 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 beta-antagonist administered immediately after defibrillation improves return of spontaneous circulation and 4-hour survival after this prolonged VF.
authors.affiliation: Cardiac Rhythm Management Laboratory, Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, AL 35294-0019, USA. crk@crml.uab.edu
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: Killingsworth
authors.forename: Chih-Chang
authors.initials: CC
authors.lastname: Wei
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ardell
authors.forename: Melody A
authors.initials: MA
authors.lastname: Kingsley
authors.forename: William M
authors.initials: WM
authors.lastname: Smith
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Ideker
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Walcott
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D003131:Combined Modality Therapy; D004554:Electric Countershock; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D007700:Kinetics; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D011412:Propanolamines / Q000627:therapeutic use*; D016019:Survival Analysis; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D016277:Ventricular Function, Left
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C036604:esmolol; D009638:Norepinephrine; D004837:Epinephrine