title: Effects of calcium channel agonism by Bay-K-8644 on ventricular fibrillation threshold of isolated heart.
abstract: The hypothesis tested was that enhanced entry of calcium into cardiac cells would increase the susceptibility to ventricular fibrillation as measured by the ventricular fibrillation threshold (VFT) of the isolated perfused rat heart. Bay-K-8644 was used as a calcium-channel agonist. There was a biphasic effect with a maximal increase in left ventricular systolic pressure and oxygen uptake at a concentration of 10(-7) M. The same concentration caused a major reduction in the VFT. The bell-shaped pattern of fall of the VFT was inversely related to the effect on LV developed pressure. The changes in VFT could be dissociated from those on myocardial metabolites. Although Bay-K-8644 increased the heart rate, reduction of the VFT could also be obtained in paced hearts. The addition of ryanodine, an agent known to interrupt intracellular recycling of calcium through the sarcoplasmic reticulum, was able to abolish approximately half the effect of Bay-K-8644 on the VFT. Therefore, increased entry of calcium via the calcium channel is able to reduce VFT, acting in part through enhanced recycling of calcium through the sarcoplasmic reticulum.
authors.affiliation: Ischaemic Heart Disease Research Unit of the Medical Research Council, Cape Town, South Africa.
authors.forename: M G
authors.initials: MG
authors.lastname: Worthington
authors.forename: L H
authors.initials: LH
authors.lastname: Opie
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000503:physiopathology*
chemical_list: D012433:Ryanodine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000242:Cyclic AMP; D002118:Calcium