Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of actodigin were studied in dogs with decreased cardiac contractility or atrail flutter. When injected at 30 min invervals into dogs with barbiturate-induced heart failure, actodigin caused a marked positive inotropic action of short duration. Actodigin's pronounced but fleeting effect appears to be related to the novel attachment of its steroid nucleus alpha to the carboxyl function in the lactone. Cardiac glycosides with a conventional beta linkage of the lactone ring to the steroid nucleus (e.g., AY-22,248) had positive inotropic actions which were both slower in onset and cumulative when injected every 30 min. Apparently because of its short duration of action, actodigin was not as cardiotoxic as its isomer, AY-22,248. Lastly, a sustained atrail flutter was induced by intercaval crush and faradic atrial stimulation. Both actodigin and ouabain converted this arrhythmia to normal sinus rhythm.
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PMID:Positive inotropic and antiarrhythmic actions of actodigin in dogs (1). 92 6

Six actodigin (AY-22,241)-related semisynthetic glycosides (with the C-3 natural linkage of the lactone ring to the steroid nucleus, transposed to C-2) were assayed in failing hearts of canine heart-lung preparations. Two compounds, with additional small modifications in the steroid nucleus, were incapable of reversing heart failure. Two others, an isodigoxigenin and an isogitoxigenin derivative, were only slightly active. However, the two other actodigin-derived compounds, with methyl groups at the lactone C-4, were very active. Compound 5 had the methyl group in beta position and was 2.5 times more potent than actodigin. Compound 6, with the methyl group in alpha position, had a potency similar to that of actodigin. In the anesthetized and vagotomized dog, their toxic effects (to the point of atrioventricular dissociation) were short lasting and completely reversible. Both of these agents had a wide margin of safety (relationship between the minimal therapeutic, irregularity and lethal doses).
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PMID:Cardiac effects of six actodigin (AY-22,241)-related semisynthetic glycosides. 683 14