Long-term prenylamine therapy: effects on responses to myocardial ischaemia in the isolated rat heart.
The effects of long-term administration of prenylamine gluconate were studied to define changes induced by chronic treatment that may alter the responses of the myocardium to ischaemic stress. Prenylamine gluconate was administered orally to rats (10 mg or 100 mg/kg per day) for 2 weeks. At the end of this period, hearts were excised for perfusion studies. In comparison with gluconate-treated controls, hearts from the group treated with the lower dose of prenylamine showed a significant reduction in basal cardiac function that was not apparent in the group treated with the higher dose of prenylamine. After a period (35 min) of ischaemia stress (reduced flow), a reduction in enzyme leakage and an increase in post-ischaemic functional recovery were observed in hearts from animals treated with the lower dose of prenylamine. In contrast, hearts from the group treated with the higher dose showed no significant improvement. However, chronic prenylamine therapy was shown to reduce in a dose-dependent manner the incidence of post-ischaemic arrhythmias. Thus, although the antiarrhythmic efficacy of long-term treatment with this agent appears to be proportional to the dosage, the ability of prenylamine to reduce ischaemic damage and promote functional recovery does not show a linear relationship with the drug dose.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D003327:Coronary Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011299:Prenylamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D006003:Glycogen; D011299:Prenylamine