L'utilisation des nouveaux agents inotropes dans le traitement des défaillances cardiaques aiguës

Abstract

The drugs, new and old, useful in the treatment of acute cardiac failure, are reviewed in the light of its pathophysiological mechanisms and of the biochemical aspects of myocardial contraction. Two major classes of drugs are considered, those that stimulate cell membrane adenylcyclase, i.e. beta-agonists (dopamine, dobutamine and dopexamine) and alpha-agonists (glucagon, forskolin, calcium agonists), and those that inhibit the cellular phosphodiesterases, i.e. bipyridine derivatives (amrinone and milrinone) and imidazolone derivatives (fenoximone and piroximone). Virtually, all the inotropic agents act by increasing the entry of calcium into the cell by increasing the intracellular AMPc concentration. Dopamine has a dose-related triphasic activity. At low doses, stimulation of renal dopaminergic receptors increases renal blood flow, glomerular filtration rate and sodium clearance. At moderate doses, dopamine stimulates, for the most part, cardiac beta-adrenergic receptors. Higher doses stimulate alpha-1-adrenergic receptors, with an increase in systemic arterial and venous pressures. Dobutamine exerts a potent positive inotropic action, with little effect on vascular tone and less tachycardia than with other catecholamines, resulting in only a slight increase in myocardial oxygen consumption. The dopamine analogue, dopexamine, increases renal blood flow, myocardial contractility and produces peripheral vasodilation. The haemodynamic effects of phosphodiesterase inhibitors are similar to those of dobutamine, except that these drugs are vasodilators, their positive inotropic properties are weak and their haemodynamic effects persist for at least 8 h after a single dose in heart failure patients. Beta-adrenergic agonists should be considered as phosphodiesterase inhibitors should probably be used as second-line drugs, when beta-agonists become ineffective, or for patients with chronic congestive heart failure, especially so as it would seem that only oral preparations of phosphodiesterase inhibitors are effective in long-term treatment.