Levosimendan improves diastolic and systolic function in failing human myocardium

Ca2+-sensitizers increase myocardial contractility, but may worsen diastoli c dysfunction. Levosimendan, through its unique troponin-C interaction, may preserve diastolic function. We investigated the effects of levosimendan ( 10(-7)-10(-5) M) on diastolic and systolic function in multicellular cardia c muscle preparations from end-stage failing human hearts (1 and 2.5 Hz, 37 degrees C, 1.25 mM [Ca2+], pH 7.4). Levosimendan improved systolic functio n: at 1 Hz, developed force (F-dev) increased from 13.84 +/- 3.27 to 16.40 +/- 3.57 (10(-7) M, P < 0.05), while diastolic force (F-dia) decreased from 5.32 +/- 0.67 to 4.94 +/- 0.61 mN/mm(2) (P < 0.05). Under control conditio ns, the increase in stimulation frequency from 1 to 2.5 Hz resulted in a de crease in F-dev of - 0.51 +/- 1.80 mN/mm(2) (negative force-frequency relat ionship). Levosimendan improved this relationship: at 10-7 M, this change b ecame positive (+1.81 +/- 2.06 mN/mm(2), P < 0.05). Diastolic function was markedly improved in the presence of levosimendan; the increase in F-dia of 1.56 +/- 0.41 mN/mm(2) (control) was attenuated to 0.70 +/- 0.19 nN/mm(2) (P < 0.05). To allow for a more derailed analysis, preparations were someti mes divided into two groups, based on their force-frequency behavior. Twitc h timing parameters were accelerated by levosimendan in preparations with a negative force-frequency relationship. Levosimendan improves both systolic and diastolic function in failing human myocardium. Effects are even more pronounced at higher heart rates and under prevailing diastolic dysfunction . (C) 2000 Elsevier Science B.V. All rights reserved.