Rapid Endotoxin-induced Alterations in Myocardial Calcium Handling-Reference-Cited by-同舟云学术

Rapid Endotoxin-induced Alterations in Myocardial Calcium Handling

Published:2001-12-01 Issue:6 Volume:95 Page:1396-1405
ISSN:0003-3022
Container-title:Anesthesiology
language:en
Short-container-title:

Author:

Stamm Christof¹,Cowan Douglas B.²,Friehs Ingeborg³,Noria Sabrena⁴,del Nido Pedro J.⁵,McGowan Francis X.⁶

Affiliation:

1. Research Fellow, Departments of Anesthesia and Cardiac Surgery and Anesthesiology/Critical Care Medicine Laboratory, Children’s Hospital and Harvard Medical School.

2. Instructor, Department of Anesthesia and Anesthesiology/Critical Care Medicine Laboratory, Children’s Hospital and Harvard Medical School.

3. Research Fellow, Department of Cardiac Surgery, Children’s Hospital and Harvard Medical School.

4. Postdoctoral Fellow, Department of Laboratory Medicine and Pathobiology, University of Toronto.

5. Associate Professor, Department of Cardiac Surgery, Children’s Hospital and Harvard Medical School.

6. Associate Professor, Department of Anesthesia and Anesthesiology/Critical Care Medicine Laboratory, Children’s Hospital and Harvard Medical School.

Abstract

Background Bacterial endotoxin (lipopolysaccharide [LPS]) induces septic shock and depressed myocardial contractility. The mechanism of LPS-mediated cardiac dysfunction remains controversial. We hypothesized that LPS exerts significant effects on myocardial excitation-contraction coupling by rapid stimulation of tumor necrosis factor alpha (TNF-alpha) expression in the heart. Methods Isolated rat hearts were studied with and without recirculation of cell-free perfusate. The effects of LPS, exogenous TNF-alpha, anti-TNF-alpha antibody, and ceramidase inhibition were examined. Measurements included myocardial uptake of LPS, left ventricular contractility, myocardial oxygen consumption, intracellular calcium [Ca2+] cycling, and TNF-alpha concentrations in coronary perfusate and myocardium. Results Lipopolysaccharide was rapidly taken up by the perfused heart. With non-recirculating perfusion, LPS had no effect on contractility, oxygen consumption, coronary vascular resistance, or intracellular free calcium concentration ([Ca2+]i). However, with recirculating perfusion contractility was significantly impaired after 30 min of LPS, associated with lower [Ca2+]i levels and attenuated systolic rise in [Ca2+]i. Significant amounts of TNF-alpha accumulated in recirculating perfusate and myocardial tissue from LPS-perfused hearts. Ceramidase inhibition or neutralizing anti-TNF-alpha antibody inhibited the effects of LPS on contractility and [Ca2+]i. Recombinant rat TNF-alpha mimicked the LPS effects with faster onset. Conclusions Lipopolysaccharide exerts rapid, negative inotropic effects on the isolated whole rat heart. The reduction in contractility is associated with depressed intracellular calcium cycling. In response to LPS, TNF-alpha is rapidly released from the heart and mediates the effects of LPS via the sphingomyelinase pathway. The present study for the first time directly links LPS-stimulated TNF-alpha production, abnormal calcium cycling, and decreased contractility in intact hearts.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Link

http://pubs.asahq.org/anesthesiology/article-pdf/95/6/1396/332794/0000542-200112000-00019.pdf

Reference50 articles.

Cited by 37 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Fluids, Vasopressors and Inotropes to Restore Heart-Vessels Coupling in Sepsis: Treatment Options and Perspectives;2024-02-23

2. Fir(e)ing the Rhythm;JACC: Basic to Translational Science;2023-06

3. TRPC channels blockade abolishes endotoxemic cardiac dysfunction by hampering intracellular inflammation and Ca2+ leakage;Nature Communications;2022-12-02

4. CARDIOMYOCYTE REPROGRAMMING IN ANIMAL MODELS OF SEPTIC SHOCK;Shock;2022-11-03

5. Inodilators in septic shock: should these be used?;Annals of Translational Medicine;2020-06