Hyperactivity of the noradrenergic sympathetic system is one of the essential "compensatory"mechanisms in chronic left ventricular failure. The ensuing stimulation of myocardial beta-adrenergic receptors results in an increase of heart rate and contractility which, to some extent, counterbalances the alteration of left ventricular function, but rapidly reaches its limits: the excessive shortening of diastoles and, mostly, the increase of myocardial oxygen demand neutralize the beneficial haemodynamic effect of beta-adrenergic stimulation, especially when ischaemia is the cause of the heart failure; the chronic exposure of adrenergic receptors to noradrenaline in high concentrations leads to desensitization, to a "down regulation" which primarily affects the beta 1 receptors and spares, at least partly, the myocardial beta 2 receptors which seem to play a quantitatively important inotropic role, particularly in chronic heart failure. These new data on the physiology of the cardiac noradrenergic system have major therapeutic consequences: in practice, the positively inotropic beta-stimulants can only be used for a short period in acute episodes of heart failure; - the use of beta-blockers in low doses is now considered in the treatment of some forms of heart failure; the mechanism of their therapeutic action remains controverted, and their long-term effectiveness in a large patient population is under study; - a new pharmacological class, beta-adrenoceptor partial agonists, seems to give satisfactory clinical and haemodynamic results in mode-rate heart failure, A wider clinical evaluation is needed to determine the therapeutic role of theses new pharmacodynamic agents.
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