Mechanoenergetic effect of pimobendan in failing dog hearts

The effect of cardiotonic drugs with a calcium-sensitizing effect (Ca2+ sensitizers) on cardiac mechanoenergetics in the failing heart is not fully understood. Accordingly, we measured left ventricular (LV) contractility (Emax) and the relation between myocardial oxygen consumption (VO2) and pressure-volume area (PVA; a measure of LV total mechanical energy) before and during enhancement of contractility by infusion of dobutamine (DOB) or pimobendan (PIMO) in six cross-circulated hearts isolated from pacing-induced heart failure (FL) dogs, and compared the results with those reported in normal hearts (NL, n = 12). Although the baseline Emax was much lower in FL dogs than in NL dogs (P < 0.01), DOB and PIMO comparably enhanced Emax in the FL dogs. The O2 cost of contractility, defined as the increase in unloaded VO2 at zero PVA divided by the increase in Emax, obtained during an enhancement of contractility with DOB, was significantly higher in FL dogs than in NL dogs, suggesting that a larger amount of O2 is consumed during Ca2+ cycling with DOB in FL dogs. In contrast, the O2 cost of contractility with PIMO was similar between FL and NL dogs. Furthermore, the VO2 per minute was significantly higher with DOB (P < 0.05) than with PIMO partly because of an excessive positive chronotropic effect of DOB. We concluded that (1) PIMO exerts a positive inotropic effect comparable to that of DOB in both NL and FL dogs; (2) the O2 cost of contractility with DOB is higher in FL dogs than in NL dogs; and (3) PIMO has a relative O2-saving effect compared with DOB in FL dogs.