EFFECTS OF A NOVEL INOTROPIC AGENT, BAY-Y-5959, IN CONSCIOUS DOGS - COMPARISON WITH DOBUTAMINE AND MILRINONE

Traditional inotropic agents, e.g., those that increase myocardial con traction through enhanced cyclic AMP or those that increase contractil ity at a relatively high O-2 cost are frequently not useful in the cli nical setting. Accordingly, newer agents that operate through differen t mechanisms have been synthesized. The goal of the present study was to compare the effects of a new Ca2+ promotor, BAY y 5959, with more t raditional inotropic agents, dobutamine and milrinone, in 11 conscious dogs chronically instrumented for measurement of left, ventricular (L V) and arterial pressures, LV internal diameter, wall thickness, coron ary blood flow, and arterial and coronary sinus O-2 content. Equi-inot ropic doses of BAY y 5959 (20 mu g . kg(-1). min(-1)), dobutamine (10 mu g . kg(-1). min(-1)), and milrinone (10 mu g . kg(-1). min(-1)) wer e selected, which increased the LV rate of pressure development in sin us rhythm by 71-78% from similar baselines. Heart rate rose with dobut amine (+24 +/- 4%) and milrinone (+23 +/- 2%) but fell with BAY y 5959 (-35 +/- 3%). Dobutamine increased myocardial O-2 consumption (MVo(2) ) by 88 +/- 10%. In contrast, MVo(2) increased less with BAY y 5959 (9 +/- 3%) and milrinone (+16 +/- 5%; P < 0.05). Furthermore, mechanica l efficiency was also calculated either with direct measurement of car diac output or by pressure-volume loops. Dobutamine and milrinone did not change efficiency; however, BAY y 5959 increased efficiency by 19 +/- 5%. With the heart rate held constant, BAY y 5959 increased MVo(2) by 32 +/- 4% but still increased efficiency by 28 +/- 7%. Thus the Ca 2+ promotor BAY y 5959 has unique features that might be desirable for clinical applications where inotropic support is indicated, but incre ased MVo(2) without enhanced mechanical efficiency is deleterious.