ATP-SENSITIVE K-2 EXTRACTION DURING PROGRESSIVE ISCHEMIA IN PIG HINDLIMB( CHANNEL BLOCKADE IMPAIRS O)

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 extra ction of available O-2. This study tested the hypothesis that ATP-sens itive K+ channels play a significant role in the response of pig hindl imb to ischemia. We pump perfused the vascularly isolated but innervat ed right hindlimb of 14 anesthetized pigs with normoxic blood while me asuring 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-perfu sed hindlimb was also infused with 10 mu g . min(-1) . kg(-1) of glibe nclamide, a potent blocker of ATP-sensitive K+ channels. Control anima ls were infused with 5% glucose solution alone. Blood flow was then pr ogressively reduced in both groups in 10 steps at 10-min intervals. Gl ibenclamide had no effect on any preischemic hindlimb or systemic meas urements. Hindlimb limb V overdot O-2 and cytochrome aa(3) redox state began to decrease at a significantly higher D overdot O-2 in glibencl amide-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 ische mia in the glibenclamide group but did not change in the control group . We conclude that ATP-sensitive K+ channels may be importantly involv ed in the vascular recruitment response that tried to meet tissue O-2 needs as blood flow was progressively reduced in the pig hindlimb.