Diaphragm sarcolemmal injury is induced by sepsis and alleviated by nitric oxide synthase inhibition

Meng Chih Lin, Satoru Ebihara, Qasim E.L. Dwairi, Sabah N.A. Hussain, Liying Yang, Stewart B. Gottfried, Alain Comtois, Basil J. Petrof

    Research output: Contribution to journalArticlepeer-review

    83 Citations (Scopus)

    Abstract

    Endotoxemia is associated with impaired diaphragm contractility, and increased nitric oxide (NO) production has recently been implicated in this phenomenon. However, the precise nature of sepsis-related alterations in diaphragm myofiber function remains unclear. We tested the hypothesis that enhanced NO synthesis during sepsis produces diaphragm sarcolemmal injury with attendant abnormalities of myofiber membrane electrophysiology. Two different rat sepsis models were employed: acute (4 h) intraarterial endotoxin (LPS; 20 mg/kg) and subacute (24 h) peritonitis induced by cecal ligation and perforation (CLP). Diaphragm damage occurred after both LPS and CLP, as indicated by hyperpermeability of myofibers to a low molecular weight tracer dye, which is normally unable to penetrate the sarcolemma. Sarcolemmal injury was significantly correlated with reductions in the resting membrane potential (Em) of single diaphragm myofibers. Western analysis revealed increased diaphragmatic expression of the inducible isoform of NO synthase (iNOS) after LPS and CLP. An inhibitor of NOS activity, LNMMA, significantly decreased morphologic as well as electrophysiologic signs of myofiber membrane injury and dysfunction. Therefore, we conclude that both acute endotoxemia and subacute peritonitis models of sepsis lead to significant sarcolemmal damage and altered Em in diaphragm myofibers. These changes appear to be mediated, at least in part, through the pathway of increased nitric oxide production.

    Original languageEnglish
    Pages (from-to)1656-1663
    Number of pages8
    JournalAmerican journal of respiratory and critical care medicine
    Volume158
    Issue number5 PART I
    DOIs
    Publication statusPublished - 1998

    ASJC Scopus subject areas

    • Pulmonary and Respiratory Medicine
    • Critical Care and Intensive Care Medicine

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