Separation between vasodilation and positive inotropism by assessment of myocardial energetics in patients with dilated cardiomyopathy.
Phosphodiesterase inhibitors have vasodilating and positive inotropic properties, and these compounds may have energy saving effects due to vasodilation and energy consuming effects due to inotropism. In order to differentiate between the effects, it is necessary to relate myocardial oxygen consumption to its hemodynamic determinants. Myocardial oxygen consumption per beat was related to the following parameters: dp/dtmax, mean velocity of fiber shortening, pressure-volume work, peak developed wall stress, and stress-time integral. The best linear relationship was found between myocardial oxygen consumption per beat and the corresponding stress-time integral (r = 0.71; p less than 0.001) in patients with idiopathic dilative cardiomyopathy. Using i.v. nitroprusside as a pure vasodilator, myocardial oxygen consumption per beat and stress-time integral decreased along this established relationship. In contrast, the phosphodiesterase inhibitor enoximone given intravenously decreased the stress-time integral significantly more than the myocardial oxygen consumption per beat. We conclude from these data that phosphodiesterase inhibitors possess vasodilating properties which reduce the myocardial oxygen demand. In addition, they do have positive inotropic effects which increase the myocardial oxygen demand. Myocardial oxygen consumption always reflects the sum of both effects. The balance between the energy saving and the energy consuming effects may determine the efficacy of phosphodiesterase inhibitors, especially in the long-term treatment of chronic heart failure.
Holubarsch
C
C
Medizinische Universitätsklinik, Innere Medizin III, Kardiologie, Universität Freiburg, FRG.
Hasenfuss
G
G
Allgeier
M
M
Heiss
H W
HW
Just
H
H
D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D017335:Enoximone; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D007093:Imidazoles; D014665:Vasodilator Agents; D009599:Nitroprusside; D017335:Enoximone