Influence of phosphodiesterase inhibition on myocardial energetics in dilative cardiomyopathy.
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.
D009202:Cardiomyopathies / Q000378:metabolism / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D017335:Enoximone; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D017335:Enoximone