INTRACORONARY LEVOSIMENDAN ENHANCES CONTRACTILE FUNCTION OF STUNNED MYOCARDIUM

A decrease in myofilament sensitivity to Ca2+ has been proposed as a m echanism for reversible contractile dysfunction after ischemia and rep erfusion. The direct actions of intracoronary myofilament Ca2+ sensiti zers on stunned myocardium have not been examined. Barbiturate-anesthe tized dogs (n = 9) were instrumented for measurement of left ventricul ar (LV) and aortic blood pressure, cardiac output, left anterior desce nding coronary artery (LAD) blood flow velocity, and subendocardial se gment length (percent segment shortening [%SS]). Dogs were subjected t o five 5-min LAD occlusions interspersed by 5-min reperfusions. Three hours after the final reperfusion, levosimendan (1.5, 3, 6, and 12 mu g/min) was administered via an intracoronary catheter. Hemodynamic eff ects and regional myocardial function were determined under control co nditions, during each LAD occlusion and reperfusion, 3 h after final r eperfusion, and after 10 min equilibration at each dose of levosimenda n. Three hours after the final reperfusion, %SS and the ratio of effec tive to total regional work were significantly (P < 0.05) decreased, a nd postsystolic shortening area was increased, consistent with myocard ial stunning. Ln stunned myocardium, intracoronary levosimendan caused dose-dependent increases in %SS (2 +/- 1 at 3 h after reperfusion to 13% +/- 2% during 12 mu g/min), abolished postsystolic shortening area , and restored the ratio of effective to total regional work while pro ducing minimum systemic hemodynamic effects.