Levosimendan improves contractility in vivo and in vitro in a rodent model of post-myocardial infarction heart failure.

AIM

As few studies have presented a thorough analysis of the effect of levosimendan (LEV) on contractility, our purpose was to investigate in vivo cardiac function as well as in vitro cardiomyocyte function and calcium (Ca(2+) ) handling following LEV treatment.

METHODS

Rats with post-myocardial infarction heart failure (HF) induced by ligation of the left anterior descending coronary artery and sham-operated animals were randomized to the infusion of LEV (2.4 μg kg(-1) min(-1) ) or vehicle for 40 min. Echocardiographic examination was coupled to pressure-volume sampling in the left ventricle before (B) and after (40 min) infusion. Isolated left ventricular cardiomyocytes were studied in an epifluorescence microscope.

RESULTS

HF LEV (n = 6), HF vehicle (n = 7), sham LEV (n = 5) and sham vehicle (n = 6) animals were included. LEV infusion compared to vehicle in HF animals reduced left ventricular end-diastolic pressure and mean arterial pressure (both P < 0.001) and improved the slope of the preload-recruitable stroke work (P < 0.05). Administrating LEV to HF cardiomyocytes in vitro improved fractional shortening and Ca(2+) sensitivity index ratio, and increased the diastolic Ca(2+) (all P < 0.01).

CONCLUSION

In HF animals, LEV improved the contractility by increasing the Ca(2+) sensitivity. Furthermore loading conditions were changed, and LEV could consequently change organ perfusion. An observed increase in diastolic Ca(2+) following LEV treatment and clinical implications of this should be further addressed.