Mechanisms of Ischemic Preconditioning in Skeletal Muscle

Abstract 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, IP, and I–R; [ R ]-N 6 -[1-methyl-2-phenylethyl]adenosine (R-PIA) and I–R; adenosine and I–R; and glibenclamide, IP, 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 IP 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 IP-induced protection. Pretreatment with the adenosine A 1 receptor agonist 8-( p -sulfophenyl)-theophyllin (8-SPT) or with adenosine did not improve postischemic muscle function. The adenosine receptor agonist did not block IP-induced protection against ischemic damage. Conclusions. The results show significant improvements in postischemic skeletal muscle function after IP or cromakalim pretreatment but they do not support a role for K ATP channels or for adenosine receptors in IP of skeletal muscle.