Role of the vascular endothelium in oxygen extraction during
progressive ischemia in canine skeletal muscle.
Curtis, Scott E., Benoit Vallet, Mark J. Winn, James B. Caufield,
Cheryl E. King, Christopher K. Chapler, and Stephen M. Cain.
DEPARTMENTS OF PEDIATRICS, PHYSIOLOGY AND BIOPHYSICS, PHARMACOLOGY
AND PATHOLOGY, UNIVERSITY OF ALABAMA AT BIRMINGHAM, BIRMINGHAM
ALABAMA, 35294 AND THE DEPARTMENT OF PHYSIOLOGY, QUEEN'S UNIVERSITY,
KINGSTON, ONTARIO, K7L 3N6
APStracts 2:0270A, 1995.
Oxygen uptake (o2) is defended during decreased oxygen delivery (o2)
by an increase in the O2 extraction ratio (O2ER, o2/o2), presumably
by recruitment of capillaries. This study tested the hypothesis that
activity of the microvascular endothelium plays a necessary role in
achieving maximal O2ER. We pump-perfused the vascularly-isolated
hindlimb of 24 anesthetized and paralyzed dogs at progressively lower
flows over a 90 min period. In 8 dogs, hindlimb vascular endothelium
was removed by injecting deoxycholate (DOC) into the perfusing artery
prior to the ischemic challenge. DOC treatment resulted in loss of
normal in vivo and in vitro endothelial-dependent dilatory responses
to acetylcholine but endothelial-independent vascular smooth muscle
responses were intact. Eight other dogs were pre-treated with L-NAME
plus indomethacin (L-I group) to block the synthesis of the
vasodilators nitric oxide and prostacyclin. L-I and DOC treatment
were associated with a 16817% and 6312% increase in hindlimb vascular
resistance, respectively. O2ER at critical o2 (the o2 at which o2
begins to decrease) was 812% in 8 control dogs, 666% in L-I, and 424%
in DOC, indicating a significant oxygen extraction defect in the two
treatment groups. These data suggest that products of the vascular
endothelium play an important role in the matching of oxygen supply
to demand during supply limitation in skeletal muscle.
Received 8 August 1994; accepted in final form 16 May 1995.
APS Manuscript Number A816-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.