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Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1196-1204

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

NAJAH ABI-GERGES, BENOIT TAVERNIER, ALEXANDRE MEBAZAA, VALÉRIE FAIVRE, XAVIER PAQUERON, DIDIER PAYEN, RODOLPHE FISCHMEISTER, and PIERRE-FRANÇOIS MÉRY

INSERM U-446, Laboratoire de Cardiologie Cellulaire et Moléculaire, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry; Département d'Anesthésie-Réanimation Chirurgicale 2, Hôpital Claude Huriez, CHU-Lille, Lille; and Département d'Anesthésie-Réanimation, Hôpital Lariboisière, AP-HP, IFR Circulation-Lariboisière, Paris, France

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 beta -adrenergic agonist (isoproterenol) on ICa was increased 12 h after EDTX injection. This change in the beta -adrenergic effect declined 24 h later. The potentiation in the beta -adrenergic stimulation of ICa was mimicked by L858051 (10 µM), a direct activator of adenylyl cyclase, but not by IBMX (200 µM), 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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 Innate ImmunityHome page
H. Schmidt, J. Saworski, K. Werdan, and U. Muller-Werdan
Decreased beating rate variability of spontaneously contracting cardiomyocytes after co-incubation with endotoxin
Innate Immunity, December 1, 2007; 13(6): 339 - 342.
[Abstract] [PDF]


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Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 1999 American Thoracic Society