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.
Jamali
I N
IN
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
Kersten
J R
JR
Pagel
P S
PS
Hettrick
D A
DA
Warltier
D C
DC
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003331:Coronary Vessels; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D017682:Myocardial Stunning / Q000503:physiopathology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D000077464:Simendan
D002316:Cardiotonic Agents; D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D000077464:Simendan