Related Experiment Videos
Augmentation of diastolic function with phosphodiesterase inhibition in congestive heart failure
P F Binkley1, P B Shaffer, J M Ryan
1Department of Medicine, Ohio State University, Columbus.
Insights
Phosphodiesterase inhibition with enoximone improved both systolic and diastolic function in patients with dilated cardiomyopathy. This inotropic agent enhanced ejection fraction and peak filling rates, aiding hemodynamic restoration.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Phosphodiesterase inhibition influences cellular calcium handling, affecting myocardial contraction and relaxation.
- Dilated cardiomyopathy is characterized by impaired systolic and diastolic ventricular function.
Purpose of the Study:
- To evaluate the effects of phosphodiesterase inhibition on ventricular function in patients with dilated cardiomyopathy.
- To test if phosphodiesterase inhibition augments both diastolic and systolic ventricular function.
Main Methods:
- Patients with dilated cardiomyopathy underwent radionuclide ventriculography to assess ejection fraction and peak diastolic filling rate.
- Measurements were taken at baseline and after 3 months of therapy with either enoximone or placebo.
Main Results:
- Enoximone significantly increased ejection fraction (11 +/- 14 units) compared to placebo (0.2 +/- 5 units).
- Enoximone significantly increased peak filling rate (0.9 +/- 0.5 to 1.4 +/- 0.5 end-diastolic volumes/sec).
- Placebo group showed no significant changes in ejection fraction or peak filling rate.
Conclusions:
- Enoximone augmented both diastolic and systolic function in dilated cardiomyopathy.
- This effect is consistent with cellular mechanisms and may restore normal hemodynamic status.
Abstract:
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.