Role of ATP-sensitive K+ channels in ischemic preconditioning of skeletal muscle against infarction.
We studied the role and mechanism of ATP-sensitive K+ (KATP) channels in ischemic preconditioning (IPC) of skeletal muscle against infarction in vivo. Surgically denervated, noncontractile latissimus dorsi muscle flaps in pentobarbitone-anesthetized pigs were assigned to nine groups: control; IPC (3 cycles of 10-min ischemia/reperfusion); preischemic lemakalim (LMK, 0.18 mg/muscle); postischemic LMK; sodium 5-hydroxydecanoate (5-HD, 27 mg/muscle) before IPC; glibenclamide (Glib 0.3 mg/kg iv) before IPC; 5-HD before preischemic LMK; 5-HD before ischemia; and Glib before ischemia. Except for Glib, all drugs were delivered to each muscle by 10-min local intraarterial infusion to avoid systemic effects. All muscle flaps underwent 4 h of global ischemia. Infarction was assessed at 48 h of reperfusion. In a separate study, muscle biopsies were taken before, during, and after ischemia for assay of high-energy phosphate and lactate contents and myeloperoxidase (MPO) activity. It was observed that muscle infarction in the IPC (24 +/- 2%) and preischemic LMK (21 +/- 2%) groups were smaller (P < 0.05) than that in the control (42 +/- 2%). The anti-infarction effect of IPC and LMK was blocked by 5-HD or Glib. IPC and preischemic LMK caused a higher (P < 0.05) muscle content of ATP and energy charge potential, a lower (P < 0.05) muscle content of lactate during ischemia, and a lower (P < 0.05) muscle MPO activity throughout 16 h of reperfusion compared with the control. These observations indicated for the first time that KATP channels are also involved in the anti-infarction effect of IPC in noncontractile skeletal muscle in vivo. Presently, the cause and importance of energy-sparing and neutrophil-inhibitory effects of IPC and LMK are not known.
Pang
C Y
CY
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Neligan
P
P
Xu
H
H
He
W
W
Zhong
A
A
Hopper
R
R
Forrest
C R
CR
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004734:Energy Metabolism / Q000187:drug effects*; D019271:Hypoxanthine / Q000378:metabolism; D007238:Infarction / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D019194:Ischemic Preconditioning / Q000379:methods*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology*; D015424:Reperfusion; D013524:Surgical Flaps; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D014970:Xanthines; D010725:Phosphocreatine; D019806:Cromakalim; D019820:Xanthine; D019271:Hypoxanthine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate