Inhibition by simulated ischemia or hypoxia of delayed afterdepolarizations provoked by cyclic AMP: significance for ischemic and reperfusion arrhythmias.
Controversy exists about the role of an increased level of tissue cyclic adenosine 3'-5' monophosphate (cAMP) in the genesis of early ischemic ventricular arrhythmias. Evidence for an arrhythmogenic role for cAMP was proposed by Podzuweit et al. (1978) and Opie et al. (1979) who argued that ischemic ventricular fibrillation was associated with increased levels of tissue cAMP in the ischemic zone. Lubbe et al. (1978) found that infusion of dibutyryl (dBcAMP), or the beta-adrenergic stimulant epinephrine, or the phosphodiesterase inhibitor theophylline, all produced a marked fall in the ventricular fibrillation threshold and an increase in the duration of the vulnerable period of the isolated perfused rat heart. In contrast, Muller et al. (1986) recently showed that prevention of ventricular fibrillation by beta-adrenergic blockade is not directly associated with decreased levels of cAMP, while Manning et al. (1985) used forskolin to stimulate adenylate cyclase and found that the markedly elevated tissue cAMP levels in the rat heart did not promote ischemic or reperfusion arrhythmias. Some of these contradictions could be resolved if the electrophysiological mechanisms by which increased levels of cAMP might predispose to arrhythmias were better understood. It is known that intracellular injection of cAMP into cardiac myocytes can enhance delayed afterdepolarizations (DADs; Matsuda et al. 1982) and that DADs may explain certain arrhythmias such as those evoked by digitalis toxicity (Ferrier, 1977) or reperfusion (Ferrier et al. 1985).(ABSTRACT TRUNCATED AT 250 WORDS)
Saman
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Ischaemic Heart Disease Research Unit, University of Capetown, Medical School, Observatory, South Africa.
Coetzee
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WA
Opie
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LH
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D003994:Bucladesine / Q000494:pharmacology; D003327:Coronary Disease / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D010477:Perfusion
D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol