METHODS AND 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.