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Influence of phosphodiesterase inhibition on myocardial energetics in dilative cardiomyopathy
G Hasenfuss1, C Holubarsch, W H Heiss
1Department of Internal Medicine, University of Freiburg, F.R.G.
Insights
Enoximone, a phosphodiesterase inhibitor, reduced cardiac workload and improved hemodynamics in patients with dilative cardiomyopathy. However, it decreased myocardial contraction economy, suggesting potential negative effects on heart energy efficiency.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Idiopathic dilative cardiomyopathy (IDCM) is characterized by impaired left ventricular function.
- Phosphodiesterase (PDE) inhibitors are used to improve cardiac performance.
- The specific effects of enoximone on myocardial energetics in IDCM require further elucidation.
Purpose of the Study:
- To investigate the effects of enoximone on left ventricular (LV) hemodynamics and myocardial energetics in patients with IDCM.
- To assess the impact of PDE inhibition on cardiac workload and oxygen consumption.
- To evaluate the changes in myocardial contraction economy.
Main Methods:
- A study involving 10 patients diagnosed with IDCM.
- Intravenous administration of enoximone.
- Measurement of LV systolic pressure, end-diastolic pressure, end-diastolic volume, heart rate, and LV systolic stress-time integral.
- Calculation of myocardial oxygen consumption and myocardial contraction economy.
Main Results:
- Enoximone significantly reduced LV systolic pressure, end-diastolic pressure, and end-diastolic volume.
- LV pressure-volume work and heart rate increased significantly.
- Myocardial oxygen consumption per beat decreased by 18%, while LV systolic stress-time integral decreased by 49%.
- Myocardial contraction economy was significantly reduced after enoximone administration.
Conclusions:
- Enoximone demonstrates both vascular and myocardial effects in patients with IDCM.
- The drug leads to a decreased economy of myocardial contraction, potentially impacting cardiac efficiency.
- Further research into the molecular mechanisms underlying these energetic changes is warranted.
Abstract:
The effects of inhibition of phosphodiesterase by enoximone on left ventricular haemodynamics and myocardial energetics were investigated in 10 patients with idiopathic dilative cardiomyopathy. After intravenous administration of enoximone, there was a significant reduction of left ventricular systolic pressure from 126 +/- 21 to 93 +/- 16 mm Hg, of left ventricular end-diastolic pressure from 16 +/- 8 to 5 +/- 3 mm Hg and of left ventricular end-diastolic volume from 287 +/- 54 to 215 +/- 69 ml. Left ventricular pressure-volume work decreased significantly from 12.1 +/- 3.6 to 7.6 +/- 2.8 mm Hg.l. Heart rate was 87 +/- 17 before and 103 +/- 18 min-1 after administration of enoximone (p less than 0.01). Left ventricular systolic stress-time integral, a major determinant of myocardial oxygen consumption, decreased by 49% from 91 +/- 32 to 46 +/- 15 10(3) dyn.s/cm2 (p less than 0.01). In contrast myocardial oxygen consumption per beat was reduced by only 18%, from 138 +/- 28 to 113 +/- 17 microliters O2/100 g (p less than 0.01). The economy of myocardial contraction as calculated by the ratio of systolic stress-time integral to myocardial oxygen consumption per beat was 675 +/- 192 before and 370 +/- 128 dyn.s.100 g/cm2.microliter O2 after administration of enoximone. In conclusion, the phosphodiesterase inhibitor enoximone exhibits vascular and myocardial effects. The myocardial effects result in decreased economy of myocardial contraction. The possible molecular mechanisms of these energetic changes are discussed.