Ischemic preconditioning attenuates capillary no-reflow induced by prolonged ischemia and reperfusion.
Ischemic preconditioning (IPC) refers to a phenomenon in which a tissue is rendered resistant to the deleterious effects of prolonged ischemia and reperfusion by prior exposure to brief, repeated periods of vascular occlusion. The purposes of this study were to determine whether IPC would reduce the extent of capillary no-reflow in postischemic skeletal muscle and whether the protective effect of IPC was due to activation of ATP-sensitive potassium (KATP) channels. To address the first aim, capillary perfusion was assessed in vascularly isolated canine gracilis muscles subjected to 4.5 h of continuous perfusion, 4 h of ischemia followed by 30 min of reperfusion (I-R), and IPC (4 periods of 5 min ischemia followed by 5 min reperfusion) before I-R. I-R was associated with a reduction in the number of patent capillaries per fiber (0.6 +/- 0.1) relative to nonischemic control muscles (2.5 +/- 0.1), an effect that was attenuated by IPC (1.3 +/- 0.1 patent capillaries fiber). A role for KATP channels in the protective effect of IPC is supported by the observation that administration of a KATP channel antagonist (glibenclamide) 10 min before induction of IPC abolished the protective effect of preconditioning (0.6 +/- 0.1 patent capillaries/fiber). On the other hand, treatment of nonpreconditioned muscles with a KATP channel agonist (pinacidil) mimicked the protection afforded by IPC (1.2 +/- 0.1 patent capillaries/fiber). Moreover, the protective effect of pinacidil treatment was reversed by prior administration of glibenclamide (0.5 +/- 0.1 patient capillaries/fiber). These data indicate that IPC improves postischemic capillary perfusion by a mechanism that involves activation of KATP channels.
Jerome
S N
SN
Department of Physiology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130, USA.
Akimitsu
T
T
Gute
D C
DC
Korthuis
R J
RJ
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002196:Capillaries / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D020110:Pinacidil; D015221:Potassium Channels / Q000502:physiology; D012039:Regional Blood Flow; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide