Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake.
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.


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-microg/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.
Michaels
Andrew D
AD
Division of Cardiology, Department of Medicine, University of California at San Francisco Medical Center, San Francisco 94143-0124, USA. andrewm@medicine.ucsf.edu
McKeown
Barry
B
Kostal
Michael
M
Vakharia
Kalpesh T
KT
Jordan
Mark V
MV
Gerber
Ivor L
IL
Foster
Elyse
E
Chatterjee
Kanu
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011724:Pyridazines / Q000008:administration & dosage*; D012039:Regional Blood Flow / Q000187:drug effects; D000077464:Simendan; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan