Journal of Applied Physiology
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J Appl Physiol 102: 1556-1564, 2007. First published November 30, 2006; doi:10.1152/japplphysiol.00785.2006
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Cardiorespiratory failure in rat induced by severe inspiratory resistive loading

Jeremy A. Simpson and Steve Iscoe

Department of Physiology, Queen's University, Kingston, Ontario, Canada

Submitted 14 July 2006 ; accepted in final form 29 November 2006

The mechanisms underlying acute respiratory failure induced by respiratory loads are unclear. We hypothesized that, in contrast to a moderate inspiratory resistive load, a severe one would elicit central respiratory failure (decreased respiratory drive) before diaphragmatic injury and fatigue. We also wished to elucidate the factors that predict endurance time and peak tracheal pressure generation. Anesthetized rats breathed air against a severe load (~75% of the peak tracheal pressure generated during a 30-s occlusion) until pump failure (fall in tracheal pressure to half; mean 38 min). Hypercapnia and hypoxemia developed rapidly (~4 min), coincident with diaphragmatic fatigue (decreased ratio of transdiaphragmatic pressure to peak integrated phrenic activity) and the detection in blood of the fast isoform of skeletal troponin I (muscle injury). At ~23 min, respiratory frequency and then blood pressure fell, followed immediately by secondary diaphragmatic fatigue. Blood taken after termination of loading contained cardiac troponin T (myocardial injury). Contrary to our hypothesis, diaphragmatic fatigue and injury occurred early in loading before central failure, evident only as a change in the timing but not the drive component of the central respiratory pattern generator. Stepwise multiple regression analysis selected changes in mean arterial pressure and arterial PCO2 during loading as the principal contributing factors in load endurance time, and changes in mean arterial pressure as the principal contributing factor in peak tracheal pressure generation. In conclusion, the temporal development of respiratory failure is not stereotyped but depends on load magnitude; moreover respiratory loads induce cardiorespiratory, not just respiratory, failure.

diaphragm; fatigue; heart; injury; troponin



Address for reprint requests and other correspondence: S. Iscoe, Dept. of Physiology, Queen's Univ., Kingston, Ontario, Canada K7L 3N6 (e-mail: iscoes{at}post.queensu.ca)




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J. A. Simpson, K. R. Brunt, and S. Iscoe
Repeated inspiratory occlusions acutely impair myocardial function in rats
J. Physiol., May 1, 2008; 586(9): 2345 - 2355.
[Abstract] [Full Text] [PDF]




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