Effects of levosimendan on right ventricular function and ventriculovascular coupling in open chest pigs.
OBJECTIVE
Levosimendan is a promising calcium sensitizer that potentially could be useful in settings of pulmonary vasoconstriction and right ventricular dysfunction. There is a shortage of information concerning its effects on right ventricular function and ventriculovascular coupling. The aim of the present study was to characterize the effects of levosimendan on right ventricular and pulmonary vascular function by means of pressure-volume and pulsatile flow analysis.


METHODS
Prospective laboratory investigation.


METHODS
University hospital laboratory.


METHODS
Eight landrace pigs (mean weight, 37 kg).


METHODS
Following instrumentation with biventricular conductance catheters, pulmonary and right coronary artery flow probes, a high-fidelity pulmonary pressure catheter, and a right coronary venous catheter, hemodynamic measurements were performed in baseline conditions and during levosimendan infusion at three increasing plasma concentrations (mean values, 27.5, 67.6, and 142.5 ng/mL).


RESULTS
Levosimendan increased heart rate and cardiac output, reduced systemic vascular resistance, and had a positive inotropic effect on the left ventricle and increased left ventricular mechanical efficiency. Moreover, levosimendan increased right ventricular contractility and hydraulic power. However, total pulmonary vascular resistance and characteristic impedance did not change throughout the protocol, and right ventricular mechanical efficiency decreased slightly at the highest concentration of levosimendan.


CONCLUSIONS
At clinical concentrations in the present model, levosimendan increases right ventricular contractility and performance without significantly influencing pulmonary vascular tone. Further studies are required in a model of pulmonary vasoconstriction to disclose possible pulmonary vasodilator effects of levosimendan.
D000818:Animals; D002302:Cardiac Output; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006835:Hydrazones / Q000494:pharmacology*; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D000077464:Simendan; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D016278:Ventricular Function, Right / Q000187:drug effects* / Q000502:physiology
D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan