ATP-sensitive K+ channel blockade impairs O-2 extraction during progressive ischemia in pig hindlimb

Tissues maintain O-2 consumption (V overdot O-2) when blood flow and O-2 delivery (D overdot O-2) are decreased by better matching of blood flow to meet local cellular O-2 demand, a process that increases extraction of available O-2. 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 D overdot O-2, V overdot O-2, perfusion pressure, and cytochrome aa(3) redox state. In one-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 preischemic hindlimb or systemic measurements. Hindlimb limb V overdot O-2 and cytochrome aa(3) redox state began to decrease at a significantly higher D overdot O-2 in glibenclamide-treated compared with control pigs. At this critical D overdot O-2, the O-2 extraction ratio (V overdot O-2/D overdot O-2) 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 O-2 needs as blood flow was progressively reduced in the pig hindlimb.