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


CONCLUSIONS
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.
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
S M
SM
Kolseth
N P L
NP
Rolim
Ø
Ø
Salvesen
D O
DO
Nordhaug
A
A
Wahba
M A
MA
Høydal
D000818:Animals; D002118:Calcium; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006835:Hydrazones / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000150:complications*; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077464:Simendan
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D002118:Calcium
Ca2+ sensitivity; Ca2+ transients; contractility; heart failure; inotropic drug; preload