Atp-sensitive potassium channel blockade impairs oxygen extraction
during progressive ischemia in piglet hindlimb.
Vallet, Benoit, Scott E. Curtis, Benoit Guery, Jacques Mangalaboyi,
Patrick Menager, Stephen M. Cain, Claude Chopin, Bernard A. Dupuis.
Depts of Intensive Care and Pharmacology and INSERM U279,
University of Lille, 59045 Lille, France, Depts of Physiology and
Biophysics, and Pediatrics, University of Alabama at Birmingham,
Birmingham, Alabama 35294
APStracts 2:0371A, 1995.
Tissues maintain O2 consumption (VO2) when blood flow and O2 delivery
(DO2) are decreased by better matching of blood flow to meet local
cellular O2 demand, a process that increases extraction of available
O2. This study tested the hypothesis that ATP-sensitive K+ channels
play a significant role in the response of pig hindlimb to ischemia.
We pump perfused the vascularly isolated but innervated right
hindlimb of 14 anesthetized pigs with normoxic blood while measuring
hindlimb DO2, VO2, perfusion pressure, and cytochrome a,a3 (cyta,a3)
redox state. In half of the pigs, the pump perfused hindlimb was also
infused with 10 [mu]g.min-1.kg-1 of glibenclamide, a potent blocker
of ATP-sensitive K+ channels. Control animals were infused with 5%
glucose solution alone. Blood flow was then progressively reduced in
both groups in 10 steps at 10 min intervals. Glibenclamide had no
effect on any pre-ischemic hindlimb or systemic measurements.
Hindlimb VO2 and cyta,a3 redox state began to decrease at a
significantly higher DO2 in glibenclamide treated pigs compared to
controls. At this critical DO2, the O2 extraction ratio (VO2/DO2) was
53 + 4% in the glibenclamide group and 73 + 5% in controls (p <
0.05). Hindlimb vascular resistance increased significantly with
ischemia in the glibenclamide group but did not change in controls.
We conclude that ATP-sensitive K+ channels may be importantly
involved in the vascular recruitment response that tried to meet
tissue O2 needs as blood flow was progressively reduced in the pig
hindlimb.
Received 18 August 1994; accepted in final form 18 May 1995.
APS Manuscript Number A874-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.