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(Circulation. 2005;111:1504-1509.)
© 2005 American Heart Association, Inc.

Heart Failure

Effects of Intravenous Levosimendan on Human Coronary Vasomotor Regulation, Left Ventricular Wall Stress, and Myocardial Oxygen Uptake

Andrew D. Michaels, MD; Barry McKeown, MD; Michael Kostal, MD; Kalpesh T. Vakharia, BA, BSE; Mark V. Jordan, MD; Ivor L. Gerber, MD; Elyse Foster, MD; Kanu Chatterjee, MB

From the Division of Cardiology, Department of Medicine, University of California at San Francisco Medical Center, San Francisco.

Correspondence to Andrew D. Michaels, MD, FACC, Division of Cardiology, University of California at San Francisco Medical Center, 505 Parnassus Ave, Box 0124, San Francisco, CA 94143-0124. E-mail andrewm{at}medicine.ucsf.edu

Received September 4, 2004; revision received November 20, 2004; accepted January 10, 2005.

Background— Levosimendan is a calcium-sensitizing agent and an inodilator under current investigation in the treatment of decompensated heart failure. The effects of intravenous levosimendan on the human coronary vasculature, together with myocardial wall stress and oxygen uptake, have not been adequately studied.

Methods and Results— Ten adult patients underwent right- and left-heart catheterization. Baseline coronary blood flow was determined with quantitative coronary angiography and an intracoronary Doppler-tipped guidewire. Myocardial oxygen uptake was measured with a coronary sinus catheter. Echocardiography was performed before and 30 minutes after an intravenous infusion of levosimendan (24-µg/kg bolus over 10 minutes) was begun. Pulmonary capillary wedge decreased 37% (P=0.009), cardiac output increased 9% (P=0.04), and systemic vascular resistance decreased 18% (P<0.001). Left ventricular ejection fraction increased 20% (P=0.009), and meridional systolic wall stress decreased 48% (P=0.009). Coronary artery diameter increased 10% at 15 minutes (P=0.001) and 11% at 30 minutes (P=0.01). Coronary artery velocity increased 10% over baseline (P=0.04). Coronary blood flow increased 45% (P=0.02), whereas coronary resistance decreased 36% at 30 minutes (P=0.03). Myocardial oxygen extraction decreased 9% at 30 minutes (P=0.04).

Conclusions— Levosimendan given intravenously exerts vasodilator effects on human coronary conductance and resistance arteries. Despite a decrease in coronary perfusion pressure, coronary blood flow is increased. A reduction in coronary vascular resistance and a decrease in coronary venous oxygen content indicate primary coronary vasodilation by levosimendan. Improved left ventricular systolic function and decreased myocardial oxygen extraction suggest improved myocardial efficiency.

Key Words: blood flow • heart failure • hemodynamics • inotrope • vasodilator agents

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