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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 295/5/R1695    most recent 90429.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Oliver, S. R. Articles by Clanton, T. L. Search for Related Content PubMed PubMed Citation Articles by Oliver, S. R. Articles by Clanton, T. L.

TEMPERATURE AND FEVER

Thermal tolerance of contractile function in oxidative skeletal muscle: no protection by antioxidants and reduced tolerance with eicosanoid enzyme inhibition

¹University of Florida, Department of Applied Physiology and Kinesiology, Gainesville, Florida; and ²The Ohio State University, The Dorothy M. Davis Heart and Lung Research Institute, Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Columbus Ohio

Submitted 16 May 2008 ; accepted in final form 26 August 2008

Mechanisms for the loss of muscle contractile function in hyperthermia are poorly understood. This study identified the critical temperature, resulting in a loss of contractile function in isolated diaphragm (thermal tolerance), and then tested the hypotheses 1) that increased reactive oxygen species (ROS) production contributes to the loss of contractile function at this temperature, and 2) eicosanoid metabolism plays an important role in preservation of contractile function in hyperthermia. Contractile function and passive force were measured in rat diaphragm bundles during and after 30 min of exposure to 40, 41, 42 or 43°C. Between 40 and 42°C, there were no effects of hyperthermia, but at 43°C, a significant loss of active force and an increase in passive force were observed. Inhibition of ROS with the antioxidants, Tiron or Trolox, did not inhibit the loss of contractile force at 43°C. Furthermore, treatment with dithiothreitol, a thiol (-SH) reducing agent, did not reverse the effects of hyperthermia. A variety of global lipoxygenase (LOX) inhibitors further depressed force during 43°C and caused a significant loss of thermal tolerance at 42°C. Cyclooxygenase (COX) inhibitors also caused a loss of thermal tolerance at 42°C. Blockage of phospholipase with phospholipase A₂ inhibitors, bromoenol lactone or arachidonyltrifluoromethyl ketone failed to significantly prevent the loss of force at 43°C. Overall, these data suggest that ROS do not play an apparent role in the loss of contractile function during severe hyperthermia in diaphragm. However, functional LOX and COX enzyme activities appear to be necessary for maintaining normal force production in hyperthermia.

diaphragm; lipoxygenase; cyclooxygenase; phospholipase A₂; heat stress