Interaction of BAY K-8644 with effects of digoxin in the dog heart-lung preparation. 1988

E Seifen, and R H Kennedy, and A B Seifen
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.

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.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D004077 Digoxin A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) Digacin,Digitek,Digoregen,Digoxina Boehringer,Digoxine Nativelle,Dilanacin,Hemigoxine Nativelle,Lanacordin,Lanicor,Lanoxicaps,Lanoxin,Lanoxin-PG,Lenoxin,Mapluxin,Boehringer, Digoxina,Lanoxin PG,Nativelle, Digoxine,Nativelle, Hemigoxine
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005260 Female Females
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts

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