Respiratory muscle injury, fatigue and serum skeletal troponin I in rat

Jeremy A. Simpson, Jennifer Van Eyk, Steve Iscoe

Research output: Contribution to journalArticle

Abstract

To evaluate injury to respiratory muscles of rats breathing against an inspiratory resistive load, we measured the release into blood of a myofilament protein, skeletal troponin I (sTnI), and related this release to the time course of changes in arterial blood gases, respiratory drive (phrenic activity), and pressure generation. After ∼1.5 h of loading, hypercapnic ventilatory failure occurred, coincident with a decrease in the ratio of transdiaphragmatic pressure to integrated phrenic activity (Pdi/ ∫ Phr) during sighs. This was followed at ∼1.9 h by a decrease in the Pdi/∫ Phr ratio during normal loaded breaths (diaphragmatic fatigue). Loading was terminated at pump failure (a decline of Pdi to half of steady-state loaded values), ∼2.4 h after load onset. During 30 s occlusions post loading, rats generated pressure profiles similar to those during occlusions before loading, with comparable blood gases, but at a higher neural drive. In a second series of rats, we tested for sTnI release using Western blot-direct serum analysis of blood samples taken before and during loading to pump failure. We detected only the fast isoform of sTnI, release beginning midway through loading. Differential detection with various monoclonal antibodies indicated the presence of modified forms of fast sTnI. The release of fast sTnI is consistent with load-induced injury of fast glycolytic fibres of inspiratory muscles, probably the diaphragm. Characterization of released fast sTnI may provide insights into the molecular basis of respiratory muscle dysfunction; fast sTnI may also prove useful as a marker of impending respiratory muscle fatigue.

Original languageEnglish (US)
Pages (from-to)891-903
Number of pages13
JournalJournal of Physiology
Volume554
Issue number3
DOIs
StatePublished - Feb 1 2004

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ASJC Scopus subject areas

  • Physiology

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