Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K(ATP) channels. Anesth Analg 2000 Jan;90(1):5-11
Date
01/07/2000Pubmed ID
10624967DOI
10.1097/00000539-200001000-00003Scopus ID
2-s2.0-0033959417 (requires institutional sign-in at Scopus site) 248 CitationsAbstract
UNLABELLED: 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.
IMPLICATIONS: 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.
Author List
Kersten JR, Montgomery MW, Pagel PS, Warltier DCAuthors
Paul S. Pagel PhD, MS, MD Emeritus Professor in the Anesthesiology department at Medical College of WisconsinDavid C. Warltier PhD Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ATP-Binding Cassette TransportersAnimals
Cardiotonic Agents
Dogs
Glyburide
Hemodynamics
Hydrazones
Hypoglycemic Agents
KATP Channels
Microspheres
Myocardial Infarction
Potassium Channels
Potassium Channels, Inwardly Rectifying
Pyridazines
Ventricular Function, Left
