Evidence for a spinal origin of the effect of baclofen on the myocardial oxygen demand indexes

Abstract

In a previous study in anaesthetized rabbits we observed that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) elicited substantial rises in the maximum rate of change of left ventricular pressure (dP/dtmax) 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) receptor agonist, injected intravenously prevented these responses. In the present study, we show that low doses of baclofen (0.1, 0.3 and 1 microgram/kg), injected intrathecally (i.t.) at the T9 level, reduced the myocardial oxygen demand during PVN stimulation. After 0.3 microgram/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 (500 micrograms/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 spinal cord and that GABA(B) receptors probably mediate these effects by modulating the central control of cardiac function. In conclusion, baclofen might be a useful tool to prevent the centrally evoked increases of myocardial oxygen demand.

GABAergic Signaling during Spinal Cord Stimulation Reduces Cardiac Arrhythmias in a Porcine Model

“…The lowest therapeutic dose was chosen based on the literature. [30][31][32][33] For the GABA A/B receptor antagonists, 1,000 µg GABA A antagonist Bicuculline (Sigma-Aldrich, USA) or 3,000 µg GABA B antagonist CGP55845 (Sigma-Aldrich) was dissolved in 2 ml normal saline and warmed to 37°C, and was infused more than 5 minutes using a syringe pump. Given that the peak dorsal horn drug concentration occurs 30 min after intrathecal administrations, each antagonist was applied 30 min before starting ischemia-reperfusion and reapplied at 60-min intervals.…”