Analysis of oral molsidomine effects on ventricular function and dimensions in the conscious dog.
The effects of oral administration of molsidomine (50, 100 and 250 micrograms/kg) on left ventricular function, dimensions and hemodynamics were studied in chronically equipped, resting conscious dogs and compared to those of orally administered nitroglycerin (5, 10 and 20 micrograms/kg), as well as isosorbide dinitrate (50, 100 and 250 micrograms/kg). Enteral absorption of molsidomine was similar to that following intravenous administration of the compound, but was delayed in the case of both nitrates, so that restraint hemodynamic effects were noted. Molsidomine significantly decreased ventricular preload and internal heart dimensions. These effects were longer-lasting and more pronounced than those induced by either nitrate compound. Heart rate and LV dP/dtmax remained unaffected by molsidomine but increased in a dose-dependent fashion after administration of the nitrates. Left ventricular ejection phase contractility decreased with all three compounds. This effect was probably due to the reduced ventricular volumes and dimensions caused by molsidomine and isosorbide dinitrate, and to the additional tachycardia with concomitant reduction in ejection phase induced by nitroglycerin. Ejection time and stroke volume fell with all three agents but the effect occurred with a greater delay of onset and was more persistent after molsidomine. Nitroglycerin was found to increase cardiac output, initially, as a sequel of positive inotropy and chronotropy, with a subsequent decrease of cardiac output. In contrast, cardiac output fell by 28% and 30% (p less than 0.02) after administration of 250 micrograms/kg molsidomine or isosorbide dinitrate, respectively. These results suggest that molsidomine has no direct effects on myocardial hemodynamics and function in the resting, awake dog. The drug exerts its beneficial effects on heart performance by a long-lasting diminution of cardiac preload caused preferentially by dilatation of postcapillary venous vessels.
D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007408:Intestinal Absorption; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D008981:Molsidomine; D005996:Nitroglycerin / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D013558:Sydnones / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D010069:Oxadiazoles; D013558:Sydnones; D014665:Vasodilator Agents; D008981:Molsidomine; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate