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

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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/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 GABAB receptor agonist, injected intravenously prevented these responses. In the present study, we show that low doses of baclofen (0.1, 0.3 and 1 μg/kg), injected intrathecally (i.t.) at the T9 level, reduced the myocardial oxygen demand during PVN stimulation. After 0.3 μg/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 μg/kg), of saclofen, a selective GABAB 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 GABAB 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.

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Authors and Affiliations

  1. Laboratoire de Pharmacologie Cardiovasculaire et Rénale, CNRS URA 589, Faculté de Médecine, Université Louis Pasteur, 11, rrue Humann, F-67000, Strasbourg, France

    Laurent Monassier, Jean Christophe Roegel, Josiane Feldman & Pascal Bousquet

  2. Fundaçao Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Av. Brasil 4365, Caixa Postal 926, 20040, Rio de Janeiro, Brazil

    Eduardo Tibiricca

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  1. Laurent Monassier
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  2. Eduardo Tibiricca
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  3. Jean Christophe Roegel
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  4. Josiane Feldman
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  5. Pascal Bousquet
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Monassier, L., Tibiricca, E., Roegel, J.C. et al. Evidence for a spinal origin of the effect of baclofen on the myocardial oxygen demand indexes. Naunyn-Schmiedeberg's Arch Pharmacol 352, 550–556 (1995). https://doi.org/10.1007/BF00169390

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  • DOI: https://doi.org/10.1007/BF00169390

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