Effects of MCI-154, a calcium sensitizer, on left ventricular systolic and diastolic function in pacing-induced heart failure in the dog.
BACKGROUND
MCI-154 is a positive inotropic agent that increases the myofilament response to Ca2+. Whether MCI-154 has beneficial effects on left ventricular dysfunction in chronic heart failure is not known. We examined the effects of MCI-154 on left ventricular systolic and diastolic function in pacing-induced heart failure in dogs.


RESULTS
We studied eight anesthetized dogs before and 2 to 4 weeks after rapid right ventricular pacing. Left cineventriculograms with simultaneous left ventricular pressures (tip manometer) were obtained before and during intravenous administration of MCI-154 (I.O. microgram.kg-1.min-1 for 15 minutes) in the control and heart-failure states. Left ventricular volume dynamics was derived from frame-by-frame (20-ms) analyses of left ventricular angiograms. In heart failure, left ventricular contractility as assessed by shifts of the end-systolic pressure-volume ratio, evaluated by inferior vena cava occlusion, was improved by MCI-154 (+ 1.94 mm Hg/mL, P < .05) to an extent similar to that in the control state (+2.47 mm Hg/mL, P < .05). MCI-154 also accelerated left ventricular relaxation, assessed by the time constant of isovolumic pressure decay (T1/2), in both states. The absolute decrease in T1/2 with MCI-154 in heart failure was significantly greater than in the control state (-8.2 versus -3.1 ms, P < .05). In heart failure, MCI-154 shifted the left ventricular diastolic pressure-volume relation clearly downward, suggesting increased diastolic distensibility.


CONCLUSIONS
MCI-154 improved not only left ventricular systolic function but also diastolic relaxation and distensibility in a chronic heart failure model.
Teramura
S
S
First Department of Internal Medicine, Mie University, Tsu, Japan.
Yamakado
T
T
Maeda
M
M
Nakano
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002303:Cardiac Output, Low / Q000209:etiology / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003971:Diastole; D004285:Dogs; D004548:Elasticity / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology*; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D011724:Pyridazines; C052228:MCI 154; D002118:Calcium