Cardiovascular effects of chronic ifenprodil in a model of central sympathetic stimulation

In the present study we investigated the effects of a long-term treatment ( 14 days) with ifenprodil on the excitatory haemodynamic responses induced b y central pharmacological stimulation in anaesthetised rabbits. The intrace rebroventricular injection of L-glutamate (3 mg/kg) induced important rises in dP/dt(max) (32.9%), mean arterial pressure (42.6%) and in the myocardia l oxygen consumption index: the triple product (84.2%). Ifenprodil (1.5, 3 and 6 mg/kg/day, i.p.) reduced the increases in myocardial oxygen demand in duced by intracerebral L-glutamate in a dose-related manner. Interestingly, ifenprodil also reduced in a dose-dependent manner the maximum values of t he oxygen demand indices reached during the central nervous system stimulat ion. These results indicate that the long-term treatment with ifenprodil ca n reduce the myocardial oxygen consumption induced by central nervous syste m stimulation without significant depression of the resting cardiac functio n. This favourable effect of ifenprodil is in fact a consequence of the ass ociation of mild inhibitory effects on the three parameters taken into acco unt in the triple product index of myocardial oxygen consumption. (C) 2000 Editions scientifiques et medicales Elsevier SAS.