Physiologic assessment of the inotropic, vasodilator and afterload reducing effects of milrinone in subjects without cardiac disease.
Milrinone increases left ventricular (LV) shortening. Whether these changes result from vasodilation alone or from a combination of vasodilation and a positive inotropic action is controversial. Load-independent end-systolic indexes of LV contractility were measured over a wide range of aortic pressures generated by methoxamine infusion before and during milrinone administration. Sixteen studies were performed using echocardiography and calibrated carotid pulse tracings in 11 normal subjects. Milrinone loading doses of 30, 45 or 60 micrograms/kg were given intravenously over 10 minutes, followed by a maintenance infusion to achieve steady-state drug levels. Milrinone induced a dose-dependent decrease in baseline (i.e., before methoxamine) total systemic resistance (p less than 0.05) and afterload as measured by end-systolic wall stress (p less than 0.001). The associated changes in the end-systolic pressure-dimension, stress-shortening and stress-velocity of fiber shortening relations were characteristic of a positive inotropic intervention. All end-systolic indexes of LV contractility demonstrated greater inotropic effect at the higher milrinone plasma concentrations. Thus, load-independent indexes of LV contractility show that milrinone has a dose-related positive inotropic effect separate from its vasodilator (total systemic resistance) and afterload (end-systolic stress) reducing effects.
D000293:Adolescent; D000328:Adult; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004562:Electrocardiography; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects*; D011674:Pulse / Q000187:drug effects; D011728:Pyridones / Q000097:blood / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011728:Pyridones; D014665:Vasodilator Agents; D020105:Milrinone