DISPARATE INOTROPIC AND LUSITROPIC RESPONSES TO PIMOBENDAN IN CONSCIOUS DOGS WITH TACHYCARDIA-INDUCED HEART-FAILURE

Left ventricular (LV) inotropic and lusitropic responses to a calcium sensitizer, pimobendan, were compared between normal and failing heart s. Heart failure was induced by rapid ventricular pacing in 6 dogs ins trumented with a micromanometer and a conductance catheter. The effect s of pimobendan were evaluated in the conscious state before and after development of heart failure. Pimobendan dose-dependently increased t he slope of the end-systolic pressure-volume (P-V) relation (Ees) in b oth normal and failing hearts, whereas its magnitude was markedly atte nuated in failing hearts. Heart rate (HR) was increased by pimobendan in normal heart but did not change in failing heart. LV relaxation, as sessed by peak -dP/dt and the time constant of isovolumic pressure dec ay (Td), was substantially improved to the same extent in failing and normal hearts. Consequently, Ees and Td exhibited a hyperbolic relatio n over a wide range of contractility states. In normal heart, pimobend an caused a leftward shift of the diastolic P-V relation while maintai ning a similar curve. In failing heart, however, this relation shifted directly downward with a concomitant increase in end-diastolic volume , indicating a reduction in the constraints on LV distention and a res ultant increase in preload reserve. Thus, pimobendan accelerated LV is ovolumic relaxation and improved distensibility in conscious dogs with tachycardia-induced heart failure despite the marked attenuation of i notropic responses.