EVIDENCE FOR A SPINAL ORIGIN OF THE EFFECT OF BACLOFEN ON THE MYOCARDIAL OXYGEN-DEMAND INDEXES

In a previous study in anaesthetized rabbits we observed that electric al stimulation of the hypothalamic paraventricular nucleus (PVN) elici ted substantial rises in the maximum rate of change of left ventricula r pressure (dP/dt(max)) and in myocardial oxygen demand indexes (rate- pressure product and triple product), similar to the changes observed during stress or physical effort. Baclofen, a selective GABA(B) recept or agonist, injected intravenously prevented these responses. In the p resent study, we show that low doses of baclofen (0.1, 0.3 and 1 mu g/ kg), injected intrathecally (i.t.) at the T9 level, reduced the myocar dial oxygen demand during PVN stimulation. After 0.3 mu g/kg baclofen i.t., the peak value of the triple product during stimulation was 140 +/- 20 compared with 193 +/- 20 before treatment, An i.t. injection (5 00 mu g/kg), of saclofen, a selective GABA(B) receptor antagonist, did not modify the resting haemodynamics significantly but attenuated the inhibitory effects of baclofen (3 mg/kg i.v.). These results suggest that the main site of the effects of baclofen is located within the sp inal cord and that GABA(B) receptors probably mediate these effects by modulating the central control of cardiac function. In conclusion, ba clofen might be a useful tool to prevent the centrally evoked increase s of myocardial oxygen demand.