The metabolic responses from rest to steady state determine
contractile function in ischemic skeletal muscle.
Timmons, James A., Simon M. Poucher, Dumitru Constantin-Teodosiu, Ian
A. Macdonald, and Paul L. Greenhaff.
Department of Physiology and Pharmacology, University Medical
School, Queen's Medical Center, Nottingham NG7 2UH, United Kingdom;
Cardiovascular and Musculoskeletal Research Department, Zeneca
Pharmaceuticals, Macclesfield, SK10 4TG, United Kingdom
APStracts 4:0097E, 1997.
Skeletal muscle contraction during ischemia, such as that experienced
by peripheral vascular disease patients, is characterised by rapid
fatigue. Using a canine gracilis model, we tested the hypothesis that
a critical factor determining force production during ischemia is the
metabolic response during the transition from rest to steady state.
Dichloroacetate (DCA) administration prior to gracilis muscle
contraction, increased pyruvate dehydrogenase complex activation and
resulted in acetylation of 80% of the free carnitine pool to
acetylcarnitine. After 1 min of contraction, phosphocreatine (PCr)
degradation in the DCA group was 50% lower than in the control group
(P<0.05) during conditions of identical force production. Following
6 min of contraction, steady-state force production was 30% higher in
the DCA group (P<0.05) and muscle ATP, PCr and glycogen degradation
and lactate accumulation were lower (P<0.05 in all cases). It
appears, therefore, that an important determinant of contractile
function during ischemia are the mechanisms by which ATP regeneration
occurs during the rest to steady state transition period.
Received 11 November 1996; accepted in final form 27 March 1997.
APS Manuscript Number E565-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 13 May 1997