Effect of levosimendan on myocardial contractility, coronary and peripheral blood flow, and arrhythmias during coronary artery ligation and reperfusion in the in vivo pig model.
OBJECTIVE
To determine whether levosimendan, a calcium sensitiser that facilitates the activation of the contractile apparatus by calcium, improves myocardial contractile function during severe ischaemia and reperfusion without exacerbating the incidence of arrhythmias.


METHODS
Pigs were pretreated orally twice daily for 10 days with 0.08 mg/kg levosimendan or placebo. On day 11 the left main coronary artery was ligated for 30 minutes, followed by 30 minutes of reperfusion. A bolus dose of levosimendan, 11.2 microg/kg intravenously, or placebo was given 30 minutes before coronary ligation, followed by a continuous infusion of 0.2 microg/kg/min levosimendan or placebo for the remainder of the experiment.


RESULTS
During the ischaemic period, cardiac output was higher in the levosimendan group than in the placebo group (mean (SD): 2.6 (0.5) v 2.0 (0.2) l/min, p < 0.05) and systemic vascular resistance was lower (2024 (188) v 2669 (424) dyne.s(-1).cm(-5), p < 0.005). During reperfusion, cardiac output and contractility (LV(max)dP/dt (pos), 956 (118) v 784 (130) mm Hg/s, p < 0.05) were increased by levosimendan. The incidence of ischaemic ventricular fibrillation and tachycardia was similar in the two groups but there were more arrhythmic events (ventricular tachycardia and ventricular fibrillation) in the levosimendan treated group (8/12 levosimendan v 1/9 control p = 0.05).


CONCLUSIONS
Levosimendan improved cardiac output and myocardial contractility during coronary artery ligation and reperfusion. However, it increased the number of arrhythmic events during ischaemia in this model of in vivo regional ischaemia.
du Toit
E
E
MRC Inter-University Cape Heart Research Group, University of Cape Town, Cape Town, South Africa. EFDT@maties.sun.ac.za
Hofmann
D
D
McCarthy
J
J
Pineda
C
C
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D006835:Hydrazones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects*; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D000077464:Simendan; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan