title: Epinephrine increases the severity of postresuscitation myocardial dysfunction.
abstract: BACKGROUND
  Epinephrine has been the mainstay for cardiac resuscitation for more than 30 years. Its vasopressor effect by which it increases coronary perfusion pressure is likely to favor initial resuscitation. Its beta-adrenergic action, however, may have detrimental effects on postresuscitation myocardial function when administered before resuscitation because it increases myocardial oxygen consumption. In the present study, our focus was on postresuscitation effects of epinephrine when this adrenergic agent was administered during cardiopulmonary resuscitation. Postresuscitation myocardial functions were compared with those of a selective alpha-adrenergic agent, phenylephrine, when epinephrine was combined with a beta 1-adrenergic blocking agent, esmolol, and saline placebo.
  
  
  RESULTS
  Ventricular fibrillation was induced in 40 Sprague-Dawley rats. Mechanical ventilation and precordial compression was initiated either 4 or 8 minutes after the start of ventricular fibrillation. The adrenergic drug or saline placebo was administered as a bolus after 4 minutes of precordial compression. Defibrillation was attempted 4 minutes later. Left ventricular pressure, dP/dt40, and negative dP/dt were continuously measured for an interval of 240 minutes after successful cardiac resuscitation. Except for saline placebo, comparable increases in coronary perfusion pressure were observed after each drug intervention. The number of countershocks required for restoration of spontaneous circulation was significantly greater for epinephrine-treated animals (10 +/- 8) when compared with phenylephrine-treated animals (1.8 +/- 0.4, P < .01) and with animals treated with epinephrine combined with esmolol (1.6 +/- 0.9, P < .01). After resuscitation, dP/dt40 and negative dP/dt were significantly decreased and left ventricular end-diastolic pressure was significantly increased in each animal when compared with prearrest levels. However, the greatest impairment followed epinephrine, and this was associated with significantly greater heart rate and the shortest interval of postresuscitation survival of 8 +/- 4 hours, whereas placebo controls survived for 12 +/- 11 hours. Phenylephrine-treated animals survived for 41 +/- 10 hours (P < .01 versus epinephrine), and animals that received a combination of epinephrine and esmolol survived for 35 +/- 11 hours (P < .01 versus epinephrine). When the duration of untreated cardiac arrest was increased from 4 to 8 minutes, the severity of postresuscitation left ventricular dysfunction was magnified, but disproportionate decreases in postresuscitation survival were again observed with placebo and epinephrine when compared with alpha-adrenergic agonists.
  
  
  CONCLUSIONS
  In an established rodent model after resuscitation following cardiac arrest, epinephrine significantly increased the severity of postresuscitation myocardial dysfunction and decreased duration of survival. More selective alpha-adrenergic agonist or blockade of beta 1-adrenergic actions of epinephrine reduced postresuscitation myocardial impairment and prolonged survival.
authors.affiliation: Institute of Critical Care Medicine, Palm Springs, Calif 92262, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: M H
authors.initials: MH
authors.lastname: Weil
authors.forename: S
authors.initials: S
authors.lastname: Sun
authors.forename: M
authors.initials: M
authors.lastname: Noc
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: R J
authors.initials: RJ
authors.lastname: Gazmuri
mesh_terms: D000322:Adrenergic Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D016887:Cardiopulmonary Resuscitation; D004359:Drug Therapy, Combination; D004554:Electric Countershock; D004837:Epinephrine / Q000009:adverse effects* / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D010656:Phenylephrine / Q000627:therapeutic use; D011412:Propanolamines / Q000627:therapeutic use; D051381:Rats; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000628:therapy
chemical_list: D000322:Adrenergic Agonists; D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D010656:Phenylephrine; C036604:esmolol; D004837:Epinephrine