(Circulation. 1995;91:838-844.)
© 1995 American Heart Association, Inc.
Articles |
Metabolic Determinants of Defibrillation
Role of Adenosine
From the Department of Medicine and the Division of Cardiology, The New York Hospital–Cornell Medical Center, New York, NY.
Background The single most important determinant of cardiac arrest outcome is the duration of ventricular fibrillation (VF) preceding delivery of a high-energy shock, because of the adverse effect of VF duration on defibrillation threshold (DFT). Although a metabolic mechanism has been proposed, hypoxia, metabolic acidosis, or alkalosis do not adversely affect DFT. However, since (1) catecholamines and adenosine levels are markedly increased during hypoxia, (2) exogenous catecholamines decrease DFT, and (3) adenosine is a potent antagonist of the electrophysiological effects of catecholamines on ventricular myocardium, we hypothesized that release of adenosine during prolonged VF adversely affects DFT and that this effect occurs through an antiadrenergic mechanism.
Methods and Results DFT was determined in dogs during infusion of adenosine (300 µg · kg-1 · min-1) and dipyridamole (0.25 mg/kg), an adenosine uptake blocker, a regimen that resulted in adenosine levels in the myocardial effluent equivalent to those achieved after 5 minutes of VF. Adenosine increased transthoracic DFT in each dog by 49±14% (n=21) (mean±SEM) and transmyocardial DFT in a separate group of 10 dogs by 103±16%, P=.0003. Pretreatment with the specific A1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) 5 mg/kg completely abolished the effects of adenosine on DFT. The effects of adenosine on DFT were also examined in the denervated state (propranolol 0.2 mg/kg plus bilateral vagotomy). In contrast to its effect in the innervated condition, adenosine had no effect on DFT in the same dogs when denervated, 49±11 versus 53±10 J (P=NS).
Conclusions Adenosine significantly increases transthoracic and transmyocardial DFT, effects that are mediated by the A1 adenosine myocardial receptor through an antiadrenergic mechanism. These results suggest that enhanced release of adenosine during VF may have a deleterious effect on defibrillation and that intramyocardial delivery of a specific A1 adenosine antagonist during VF may facilitate defibrillation and significantly reduce defibrillation threshold.
Key Words: electrophysiology • dipyridamole • fibrillation
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