Comparison of the effects of endotoxin on limb, respiratory, and
cardiac muscle.
Supinski, G., D. Nethery, D. Stofan, A. Dimarco.
Pulmonary Division, Department of Medicine Case Western Reserve
University and Metrohealth Medical Center, Cleveland, Ohio
APStracts 3:0249A, 1996.
Recent work has shown that endotoxin administration produces
reductions in respiratory muscle contractility and an increase in
indices of free radical mediated lipid peroxidation within these
muscles. It is not known, however, if endotoxin induced lipid
peroxidation occurs only in the respiratory muscles or is a
widespread phenomenon affecting all striated muscles. To examine this
issue, we examined the effect of administration of a range of doses
of endotoxin on the isometric force generating ability and lipid
peroxidation of three muscles: the diaphragm (DIA), a leg muscle
(i.e. the flexor halluces longus, FHL), and papillary cardiac muscle
(CARD). Studies were performed on hamsters divided into groups
injected over two days with either saline, low, medium or high doses
of endotoxin. Animals were sacrificed on the third study day, force
generation by the three muscles was examined in vitro and muscles
were assayed for 8-isoprostane, an index of lipid peroxidation. We
found that endotoxin produced significant reductions in both FHL and
diaphragm force generation. For example, for control, low, medium and
high dose groups, diaphragm twitch force averaged 6.0 + 0.6, 4.3 +
0.4, 2.8 + 0.4 and 2.9 + 0.6 N/cm2, respectively (p<.0003, with
control muscles different from all endotoxin groups), while FHL
twitch force averaged 3.0 + 0.2, 1.7 + 0.2, 2.2 + 0.3 and 1.7 + 0.3
N/cm2, respectively for these groups (p<.003, with control
muscles different from endotoxin groups). CARD force generation was
unaffected, however, by endotoxin. Changes in 8-isoprostane largely
paralleled alterations in force, with endotoxin eliciting marked
increases in DIA and FHL 8-isoprostane levels but no change in CARD
8-isoprostane. For example 8-isoprostane averaged 296 + 38 and 934 +
152 picogm/gm for diaphragm muscles of control and high dose
endotoxin groups, respectively (p<.03), and averaged 254 + 35
and 681 + 69 picogm/gm for FHL muscles from these two groups
(p<.05). These findings suggest that: a) lipid peroxidation and
muscle dysfunction in response to endotoxin administration are not
limited to the respiratory muscles, but also occur in limb skeletal
muscle; and b) cardiac muscle appears to be resistant to this
particular mechanism of endotoxin induced dysfunction.
Received 13 January 1995; accepted in final form 2 May 1996.
APS Manuscript Number A52-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96