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.


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.
Gürke
L
L
Department of Surgery, University of Basel, Basel, Switzerland. lguerke@access.ch
Mattei
A
A
Chaloupka
K
K
Marx
A
A
Sutter
P M
PM
Stierli
P
P
Harder
F
F
Heberer
M
M
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
D015221:Potassium Channels; D018047:Receptors, Purinergic P1