Levosimendan enhances left ventricular systolic and diastolic function in conscious dogs with pacing-induced cardiomyopathy

We examined the left ventricular (LV) mechanical actions of levosimendan (LSM) before and after the development of pacing-induced cardiomyopathy in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, and cardiac output (CO). The slope (M-w) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), the maximal rate of segment-lengthening Velocity (dL/dt), and a regional chamber-stiffness constant (K-p) On different experimental days, dogs were assigned to receive LSM (12- or 24-mu g/kg loading dose and 0.2 or 0.4 mu g/kg/min infusion) before rapid ventricular pacing was initiated. Dogs were then paced at 240 beats/min for 22 +/- 2 days, and the low and high doses of LSM were repeated on separate days. LSM increased M-w and +dP/dt in dogs before the initiation of pacing, consistent with enhanced myocardial contractility. LSM also improved indices of LV diastolic function (decreases in tau and K-p and increases in dL/dt) in dogs before pacing. Rapid ventricular pacing over a 3-week period increased LV end-diastolic pressure and produced systolic (decreases in M-w and +dP/dt) and diastolic (increases in tau and Kp and decreases in dL/dt) dysfunction. LSM significantly (p < 0.05) increased M-w (54 +/- 3 to 98 +/- 6 mm Hg) +dP/dt and dL/dt (57 +/- 13 to 72 +/- 13 mm/s) and decreased tau (66 +/- 4 to 52 +/- 3 ms) and K-p (1.14 +/- 0.14 to 0.71 +/- 0.03 mm(-1)) in the pres- ence of LV dysfunction. In contrast to the findings in normal dogs, however, LSM did not alter heart rate and calculated in dices of myocardial oxygen consumption in dogs after pacing. The findings indicate that LSM produces favorable alterations in hemodynamics and positive inotropic and lusitropic effects in conscious dogs with left ventricular dysfunction.