Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine.
BACKGROUND
We hypothesized that the effect of pimobendan (UD-CG 115 BS) to increase calcium sensitivity of contractile protein might result in less myocardial oxygen consumption (VO2) in comparison with dobutamine when they enhance ventricular contractility to the same extent. To examine this hypothesis, we compared the effects of pimobendan and dobutamine on left ventricular contractility and energetics using the frameworks of Emax (contractility index) and the relation between VO2 and PVA (systolic pressure-volume area, a measure of left ventricular total mechanical energy).


RESULTS
We measured VO2, Emax, PVA, and force-time integral (FTI) in excised, cross-circulated, nonfailing dog hearts. The slope of the VO2-PVA relation reciprocally indicates the efficiency from PVA-dependent VO2 to the total mechanical energy (contractile efficiency). The VO2 intercept of the VO2-PVA relation, i.e., PVA-independent VO2, reflects energy utilization for excitation-contraction coupling. The ratio of FTI to PVA-dependent VO2 can be called contractile economy. Both drugs comparably enhanced Emax. Although the contractile economy was greater by 14 +/- 19% (p less than 0.05) for pimobendan than for dobutamine, the contractile efficiency was similar between the two drugs. Oxygen cost of contractility, defined as the slope of the relation between the PVA-independent VO2 and Emax, was the same between the two drugs. Other mechanoenergetic effects of both drugs were similar except for a greater coronary vasodilating effect of pimobendan.


CONCLUSIONS
Pimobendan has almost the same mechanoenergetic effects as dobutamine but slightly greater contractile economy and coronary vasodilation. The calcium-sensitizing effect of pimobendan did not save the oxygen cost of contractility.
Hata
K
K
Department of Cardiovascular Dynamics, National Cardiovascular Center, Osaka, Japan.
Goto
Y
Y
Futaki
S
S
Ohgoshi
Y
Y
Yaku
H
H
Kawaguchi
O
O
Takasago
T
T
Saeki
A
A
Taylor
T W
TW
Nishioka
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D006324:Heart Arrest, Induced; D006352:Heart Ventricles; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D011724:Pyridazines; C041648:pimobendan; D004280:Dobutamine; D011189:Potassium Chloride; D011433:Propranolol