Mechanisms of ischemic preconditioning in skeletal muscle

Background. Ischemic preconditioning (IP) (one or more cycles each consisting of a short period of ischemia and a short period of reperfusion, before the sustained ischemia) reduces ischemia-related organ damage in heart and skeletal muscle but the underlying mechanisms are not clear. This study was intended to assess the possible involvement of K-ATP channels and of adenosine receptors in IP of skeletal muscle in a rat model of skeletal muscle ischemia. Materials and methods. Groups of 8-15 rats were given the following in vivo treatments: ischemia-reperfusion (I-R: 2.5 h tourniquet-induced ischemia of the right hindlimb, then 2 h reperfusion); IP (three cycles of 5 min ischemia, then 5 min reperfusion) before I-R;cromakalim and I-R; glibenclamide, cromakalim; and I-R; glibenclamide, IF, and I-R; [R]-N-6-[1-methyl-2-phenylethyl]adenosine (R-PLA) and I-R; adenosine and I-R; and glibenclamide, IF, and I-R. Parameters of muscle function (postischemic maximal force, performance, contraction index, and force after 1 min of stimulation) were then assessed in vitro in the extensor digitorum longus muscle. Results. Pretreatment with either IF or the K-ATP channel opener cromakalim significantly improved postischemic muscle function. The protective effect of cromakalim was not seen when the K-ATP channel blocker. glibenclamide was added. Glibenclamide, however, did not block IF-induced protection. Pretreatment with the adenosine A, receptor agonist 8-(p-sulfophenyl)-theophyllin (8-SPT) or with adenosine did not improve postischemic muscle function. The adenosine receptor agonist did not block IF-induced protection against ischemic damage. Conclusions. The results show significant improvements in postischemic skeletal muscle function after IF or cromakalim pretreatment but they do not support a role for K-ATP channels or for adenosine receptors in IP of skeletal muscle. (C) 2000 Academic Press.