title: Modulation of myocardial cyclic AMP and vulnerability to fibrillation in the rat heart.
abstract: In the isolated rat heart, changes in the ventricular fibrillation threshold (VFT) relate to the myocardial cyclic AMP content rather than to the high-energy phosphate content. After coronary ligation the reduction in VFT correlates with the increase in ischemic tissue cyclic AMP. Agents that reduce the myocardial cyclic AMP (propranolol, 16 microM in perfusate, or amiodarone, 42 microM/kg pretreatment) prevent the postligation fall of the VFT without altering high-energy phosphate depletion. Conversely, theophylline (500 microM), which increases cyclic AMP in ischemic myocardium, causes a greater reduction of VFT without increasing high-energy phosphate depletion. Spontaneous ventricular tachycardia and fibrillation are uncommon in coronary ligated hearts in the first 15 min after ligation (10-20%); these arrhythmias are greatly increased either by reducing the perfusate potassium from 5.9 to 3.0 mM or by pretreating hearts with 1-methyl-3-isobutyl xanthine (10 microM), a cyclic-AMP phosphodiesterase inhibitor. Adenosine (100 microM) antagonizes the increased arrhythmogenesis in both low perfusate potassium and cyclic-AMP phosphodiesterase-inhibited hearts, in the latter without reducing the ischemic tissue cyclic AMP levels. The antiarrhythmic action of adenosine in these hearts is independent of reducing tissue cyclic AMP. Adenosine generated in ischemic myocardium may serve as an endogenous antagonist to the arrhythmogenic action of cyclic AMP.
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008026:Ligation; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000378:metabolism*
chemical_list: D013806:Theophylline; D000242:Cyclic AMP; D000241:Adenosine