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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 aa3 redox state. In one-half of the pigs, the pump-perfused hindlimb was also infused with 10 micrograms.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 preischemic hindlimb or systemic measurements. Hindlimb VO2 and cytochrome aa3 redox state began to decrease at a significantly higher DO2 in glibenclamide-treated compared with control pigs. At this critical DO2, the O2 extraction ratio (VO2/DO2) was 53 +/- 4% in the glibenclamide group and 73 +/- 5% in the control group (P < 0.05). Hindlimb vascular resistance increased significantly with ischemia in the glibenclamide group but did not change in the control group. 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.
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C Chopin, and
B A Dupuis
October 1996,
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P Menager, and
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C Chopin, and
B A Dupuis
June 1997,
The American journal of physiology,
B Vallet, and
S E Curtis, and
B Guery, and
J Mangalaboyi, and
P Menager, and
S M Cain, and
C Chopin, and
B A Dupuis
February 1992,
The Journal of pharmacology and experimental therapeutics,
B Vallet, and
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B Guery, and
J Mangalaboyi, and
P Menager, and
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C Chopin, and
B A Dupuis
January 1999,
Methods and findings in experimental and clinical pharmacology,
B Vallet, and
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B Guery, and
J Mangalaboyi, and
P Menager, and
S M Cain, and
C Chopin, and
B A Dupuis
December 1997,
The American journal of physiology,
B Vallet, and
S E Curtis, and
B Guery, and
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P Menager, and
S M Cain, and
C Chopin, and
B A Dupuis
July 2002,
Nihon rinsho. Japanese journal of clinical medicine,
B Vallet, and
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B Guery, and
J Mangalaboyi, and
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C Chopin, and
B A Dupuis
April 1980,
Journal of applied physiology: respiratory, environmental and exercise physiology,
B Vallet, and
S E Curtis, and
B Guery, and
J Mangalaboyi, and
P Menager, and
S M Cain, and
C Chopin, and
B A Dupuis
November 1997,
Stroke,
B Vallet, and
S E Curtis, and
B Guery, and
J Mangalaboyi, and
P Menager, and
S M Cain, and
C Chopin, and
B A Dupuis
July 1993,
Progress in neurobiology,
B Vallet, and
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B Guery, and
J Mangalaboyi, and
P Menager, and
S M Cain, and
C Chopin, and
B A Dupuis
January 1991,
The Japanese journal of physiology,
