Interaction of BAY K-8644 with effects of digoxin in the dog heart-lung preparation.
Concentration-dependent effects of BAY K-8644, a dihydropyridine calcium channel agonist, on heart rate (HR), left atrial pressure (LAP) and maximal rate of left intraventricular pressure rise (+dP/dtmax) were compared with those of isoproterenol and digoxin in dog heart-lung preparations during exposure to 0.8 vol% halothane. All three agents reduced LAP to nearly equal levels at maximally effective concentrations. Maximal increases in +dP/dtmax induced by BAY k-8644 and digoxin were of similar magnitude (35 and 31%, respectively), and both agents increased HR slightly. Isoproterenol elevated both +dP/dtmax and HR more than twice as much as the other agents. At a concentration which produced only small changes by itself, BAY K-8644 markedly increased the effects of digoxin on LAP and +dP/dtmax. Furthermore, the same concentration of BAY K-8644 significantly reduced toxic effects of digoxin (arrhythmogenesis, elevation of LAP, reduction in systemic output). These data indicate that in the isolated blood-perfused heart digoxin's positive inotropic action may be enhanced by an appropriate concentration of BAY K-8644, while adverse effects are diminished.
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Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
Kennedy
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004077:Digoxin / Q000008:administration & dosage*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000008:administration & dosage; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004077:Digoxin; D007545:Isoproterenol