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CARDIOVASCULAR ANESTHESIA

Levosimendan, a New Positive Inotropic Drug, Decreases Myocardial Infarct Size via Activation of K_ATP Channels

Judy R. Kersten, MD^*, Matthew W. Montgomery, BS^*, Paul S. Pagel, MD, PhD^*,,§, and David C. Warltier, MD, PhD^*,,,§

Departments of *Anesthesiology, Pharmacology, and Medicine (Division of Cardiovascular Diseases), Medical College of Wisconsin; and §Zablocki Veterans’ Affairs Medical Center, Milwaukee, Wisconsin

Address correspondence and reprint requests to Judy R. Kersten, MD, Medical College of Wisconsin, MEB-Room 462C, 8701 Watertown Plank Rd., Milwaukee, WI 53226.

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 µg/kg bolus followed by an infusion of 0.4 µg · kg^-1 · min^-1) in the presence or absence of glyburide (a K_ATP channel antagonist) pretreatment (100 µg/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.

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