title: 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.
  
  
  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.
authors.affiliation: Department of Surgery, University of Basel, Basel, Switzerland. lguerke@access.ch
authors.forename: L
authors.initials: L
authors.lastname: Gürke
authors.forename: A
authors.initials: A
authors.lastname: Mattei
authors.forename: K
authors.initials: K
authors.lastname: Chaloupka
authors.forename: A
authors.initials: A
authors.lastname: Marx
authors.forename: P M
authors.initials: PM
authors.lastname: Sutter
authors.forename: P
authors.initials: P
authors.lastname: Stierli
authors.forename: F
authors.initials: F
authors.lastname: Harder
authors.forename: M
authors.initials: M
authors.lastname: Heberer
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D006339:Heart Rate; D019194:Ischemic Preconditioning; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology
chemical_list: D015221:Potassium Channels; D018047:Receptors, Purinergic P1