EFFETS HEMODYNAMIQUES DE LA NIFEDIPINE APRES INJECTION INTRAVEINEUSE OU INTRACORONARIENNE

Nifedipine, as a calcium inhibitor, should have negative inotropic properties. Multiple experimental studies on isolated muscle fibers have demonstrated this negative inotropic effect. On the other hand, clinical experience during therapeutic use and haemodynamic investigations have not demonstrated this negative inotropic effect. This paradox was investigated by intravenous and intracoronary injections of the drug in order to dissociate its peripheral effects from its direct myocardial effects. Left ventricular pressure (LVP) at end systole (ES) and end diastole (ED), the maximal dP/dt (first derivative of the LVP), the velocity of the contractile element at rest and during atrial pacing, were measured before and after intravenous nifedipine infusion. The parameters of isovolumic contraction and relaxation were then measured on a beat-to-beat basis at constant heart rate before and after intracoronary injection. After intravenous nifedipine infusion, we observed a decrease in systemic pressure at rest, and a decrease in LVP-ED and an increase in Vmax during atrial pacing. The decrease in systemic pressure is due to peripheral vasodilation and a decrease in peripheral vascular resistance. The increased heart rate observed after intravenous injection suggests activation of the baroreceptor reflex. From a clinical point of view, this reduction in afterload, independent of the coronary haemodynamic effects, is in itself favourable. The reduction in LVP-ED and the improvement in contractility during atrial pacing suggests improved myocardial cellular metabolism. Recently, the beneficial effects of parenteral nifedipine have been confirmed in human studies in a particularly critical situation: angina refractory to treatment with beta-blockers and nitrates. Nifedipine spectacularly reduces the indications for balloon pumping, until recently the classical mode of treatment of this patient group in our institution. After intracoronary injection of nifedipine, all parameters of isovolumic contraction and relaxation were considerably depressed, and LDV-ED was significantly increased. These effects are due to the electromechanical dissociation observed experimentally after inhibition of intracellular calcium influx. This electromechanical dissociation provokes a transient cardioplegia, which is itself responsible for an important reduction in myocardial oxygen consumption. At the same time the coronary bed is vasodilated and its flow is increased. This double effect justifies intracoronary administration in two specific situations: suppression of spontaneous or catheter-induced spasm during coronary catheterisation; preventive administration before percutaneous transluminal angioplasty.