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Sequential Changes in Autonomic Regulation of Cardiac Myocytes after In Vivo Endotoxin Injection in Rat

Abstract : We report that in vivo injection of endotoxin (EDTX, 6 mg · kg− 1) induces cardiovascular alterations in rats that closely mimic the clinical situation, as assessed by in vivo hemodynamic measurements in anesthetized and conscious, chronically instrumented animals. The patch-clamp technique was used to characterize the L-type calcium current (ICa) and its autonomic regulation in isolated cardiac myocytes. The density of ICa progressively decreased at 12 and 36 h after EDTX injection. However, the dihydropyridine ( ± )Bay K 8644 (100 nM) enhanced ICa to levels similar to those in control and EDTX-treated myocytes. In addition, the net stimulatory effect of a β -adrenergic agonist (isoproterenol) on ICa was increased 12 h after EDTX injection. This change in the β -adrenergic effect declined 24 h later. The potentiation in the β -adrenergic stimulation of ICa was mimicked by L858051 (10 μ M), a direct activator of adenylyl cyclase, but not by IBMX (200 μ M), a phosphodiesterase inhibitor. Besides, the antiadrenergic effect of acetylcholine on ICa was unchanged 12 h after EDTX injection, but increased 36 h after EDTX injection. These results support the hypothesis that time-dependent changes in the adenylyl cyclase pathway in cardiac myocytes may contribute, via the autonomic regulation of ICa, to the severity of myocardial dysfunction during sepsis.
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Najah Abi-Gerges, Benoit Tavernier, Alexandre Mebazaa, Valérie Faivre, Xavier Paqueron, et al.. Sequential Changes in Autonomic Regulation of Cardiac Myocytes after In Vivo Endotoxin Injection in Rat. American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 1999, 160 (4), pp.1196-1204. ⟨10.1164/ajrccm.160.4.9808149⟩. ⟨hal-03616968⟩

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