Augmentation of diastolic function with phosphodiesterase inhibition in congestive heart failure.
Phosphodiesterase inhibition promotes both cellular uptake and release of calcium, which should thus facilitate both myocardial relaxation and myocardial contraction. To test the hypothesis that phosphodiesterase inhibition augments both diastolic and systolic ventricular function, parameters of left ventricular ejection and filling were measured in patients with dilated cardiomyopathy before and after therapy with the phosphodiesterase inhibitor enoximone. Baseline radionuclide ventriculography was performed in all subjects with derivation of left ventricular ejection fraction and peak diastolic filling rate. These parameters were again assessed after 3 months of therapy with either placebo (six patients) or enoximone (seven patients). Ejection fraction increased significantly (p less than 0.05) in the enoximone group (change from baseline = 11 +/- 14 ejection fraction units) but did not change in the placebo group (0.2 +/- 5 ejection fraction units). Enoximone administration was associated with a significant (p less than 0.05) increase in peak filling rate, from 0.9 +/- 0.5 to 1.4 +/- 0.5 end-diastolic volumes per second, which was noted in the placebo group (1.2 +/- 0.6 to 1.4 +/- 0.9 end-diastolic volumes per second; p = not significant). Thus, in comparison with placebo, exoximone augmented both diastolic and systolic function in dilated cardiomyopathy. This identifies an additional influence of this class of inotropic agent on the function of the intact ventricle that is consistent with previously described cellular mechanisms and that may significantly contribute to a restoration of normal hemodynamic status in dilated cardiomyopathy.
Binkley
P F
PF
Department of Medicine, Ohio State University, Columbus.
Shaffer
P B
PB
Ryan
J M
JM
Leier
C V
CV
D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003971:Diastole / Q000187:drug effects*; D004452:Echocardiography; D017335:Enoximone; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D011897:Random Allocation
D002316:Cardiotonic Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D017335:Enoximone