Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K(ATP) channels.
We tested the hypothesis that levosimendan, a new positive inotropic drug that activates adenosine triphosphate-regulated potassium (K(ATP)) channels in vitro, decreases myocardial infarct size in vivo. Myocardial infarct size was measured after a 60-min left anterior descending coronary artery occlusion and 3 h of reperfusion in dogs receiving either IV vehicle (0.9% saline) or levosimendan (24 microg/kg bolus followed by an infusion of 0.4 microg x kg(-1) x min(-1)) in the presence or absence of glyburide (a K(ATP) channel antagonist) pretreatment (100 microg/kg). Levosimendan increased (P < 0.05) the maximal rate of increase of left ventricular pressure and decreased myocardial infarct size from 24%+/-2% (control experiments) to 11%+/-2% of the left ventricular area at risk for infarction. Glyburide did not alter the hemodynamic effects of levosimendan but blocked levosimendan-induced reductions of infarct size. Subendocardial collateral blood flow was similar among groups. However, levosimendan increased subepicardial and midmyocardial collateral perfusion in the absence, but not in the presence, of glyburide. Levosimendan exerts cardioprotective effects via activation of K(ATP) channels at a dose that simultaneously enhances myocardial contractility.


CONCLUSIONS
Levosimendan may be advantageous in patients requiring inotropic support who are also at risk of myocardial ischemia. Activation of adenosine triphosphate-regulated potassium channels during infusion of levosimendan may produce cardioprotective effects while simultaneously enhancing ventricular contractile function.
Kersten
J R
JR
Department of Anesthesiology, Medical College of Wisconsin, 53226, USA.
Montgomery
M W
MW
Pagel
P S
PS
Warltier
D C
DC
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels; D008863:Microspheres; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D015221:Potassium Channels / Q000819:agonists*; D024661:Potassium Channels, Inwardly Rectifying; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D016277:Ventricular Function, Left / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D002316:Cardiotonic Agents; D006835:Hydrazones; D007004:Hypoglycemic Agents; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011724:Pyridazines; C092520:uK-ATP-1 potassium channel; D000077464:Simendan; D005905:Glyburide