Intracoronary levosimendan enhances contractile function of stunned myocardium.

A decrease in myofilament sensitivity to Ca2+ has been proposed as a mechanism for reversible contractile dysfunction after ischemia and reperfusion. The direct actions of intracoronary myofilament Ca2+ sensitizers on stunned myocardium have not been examined. Barbiturate-anesthetized dogs (n = 9) were instrumented for measurement of left ventricular (LV) and aortic blood pressure, cardiac output, left anterior descending coronary artery (LAD) blood flow velocity, and subendocardial segment length (percent segment shortening [%SS]). Dogs were subjected to five 5-min LAD occlusions interspersed by 5-min reperfusions. Three hours after the final reperfusion, levosimendan (1.5, 3, 6, and 12 microg/min) was administered via an intracoronary catheter. Hemodynamic effects and regional myocardial function were determined under control conditions, during each LAD occlusion and reperfusion, 3 h after final reperfusion, and after 10 min equilibration at each dose of levosimendan. Three hours after the final reperfusion, %SS and the ratio of effective to total regional work were significantly (P < 0.05) decreased, and postsystolic shortening area was increased, consistent with myocardial stunning. In stunned myocardium, intracoronary levosimendan caused dose-dependent increases in %SS (2 +/- 1 at 3 h after reperfusion to 13% +/- 2% during 12 microg/min), abolished postsystolic shortening area, and restored the ratio of effective to total regional work while producing minimum systemic hemodynamic effects.