Evaluation of the vasodilator vs inotropic effect of milrinone using an animal model of left ventricular failure: reversal of disopyramide depression of the myocardium with milrinone.
Milrinone (M) has been shown to improve left ventricular (LV) performance in animal and human studies. M has strong vasodilator action, and whether increased LV performance is due primarily to vasodilation or to a direct positive inotropic effect is unclear. Ten mongrel dogs were studied. Disopyramide caused a significant and sustained decrease in LV function and was a good model for myocardial depression. At equal reduction in systemic vascular resistance (SVR), M reversed this LV depression to a significantly greater degree than nitroprusside (NP) did. At equal levels of vasodilation, M produced significantly greater improvement in indices of LV function than NP did in our model of disopyramide-induced LV failure. This suggest that its effect on LV function is not due entirely to afterload reduction, or to reflex sympathetic stimulation, but has a substantial component of direct inotropic stimulation. This study also demonstrated a reversal of disopyramide-induced LV dysfunction by M, which may be clinically useful since, as in many antiarrhythmics, myocardial depression may be a limiting factor in its use.
Goldberg
E
E
Department of Medicine, Beth Israel Medical Center, Mount Sinai School of Medicine, City University of New York, New York.
Berdoff
R
R
Spivack
G
G
Haimowitz
A
A
Tay
S
S
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004195:Disease Models, Animal; D004206:Disopyramide / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011728:Pyridones; D014665:Vasodilator Agents; D009599:Nitroprusside; D004206:Disopyramide; D020105:Milrinone