Central and Regional Vascular Hemodynamics Following Intravenous Milrinone in the Conscious Rat

Abstract

This study examined the hemodynamic and regional vascular profile of intravenous (i.v.) milrinone during increasing doses (3, 6, 12 .mu.g/kg/min, n = 8) and by intraindividual comparison of milrinone and dobutamine (n = 10) in normal conscious rats. At 3 .mu.g/kg/min, Milrinone increased coronary and cerebral blood flow (radioactive microspheres 15 .+-. 5 .mu.m) (7.7-9.8 and 1.05-1.27 ml/min/g respectively, both p < 0.05) without significant changes in systemic hemodynamics. At 6 .mu.g/kg/min milrinone increased skeletal muscle blood flow (0.19-0.24 ml/min/g, p < 0.05) along with increases in cardiac output, stroke volume, and stroke work (all p < 0.05), while systemic vascular resistance decreased (-51%, p < 0.05). When compared with dobutamine, milrinone caused a greater increase in cardiac output (+26% vs. +17%) and a greater reduction in systemic vascular resistance. Milrinone and dobutamine increased renal, intestinal, cerebral, and coronary flow to a similar extent, but only milrinone enhanced hepatic arterial blood flow (+26%, p < 0.05) and tended to increase flow to skeletal muscle (+35%, p = 0.07). We conclude that milrinone exerts significant regional vasodilating effects in a conscious rat model, being most prominent in the coronary and cerebral circulations at a dosage that does not alter central hemodynamics. At higher doses, milrinone causes a balanced increase in regional blood flow including enhanced flow to skeletal muscle. The hemodynamic (particularly as compared with dobutamine) and regional vascular profile of milrinone suggests a predominant vasodilating effect in the rat. Given a similar limited response of rat and diseased human myocardium to milronine, these findings may have important clinical implications.