Role of ATP-sensitive K+ channels in ischemic preconditioning of skeletal muscle against infarction

Abstract

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.

Mitochondrial KATPchannels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction

“…We observed previously in the pig that 8 ϫ 13 cm LD muscle flaps sustained 42-45% infarction when subjected to 4 h of warm ischemia and 48 h of reperfusion (1,14,28,30,31). Therefore, the same I/R time was used in the present studies.…”

Ischaemic preconditioning does not alter the determinants of endurance running performance in the heat

“…Bushell and Klenerman (2002) have mimicked the protective effects of IP through adenosine infusion. Adenosine may proffer beneficial clinical and exertional effects by acting as a vasodilator (Gustafsson et al 1993), and/or opening potassium (K ATP ) channels, which in turn preserves energy (Pang et al 1997;Cohen et al 2000). This may occur reduced mitochondrial oxygen consumption (Cooper & Brown 2008), although a reduced oxygen consumption for a given submaximal exercise intensity is not uniformly observed (De Groot et al 2010).…”

Disruption of Sur2 -containing K ATP channels enhances insulin-stimulated glucose uptake in skeletal muscle

“…The vascular K ATP channel plays a role in regulation of vascular tone, and treatment with agents such as diazoxide and pinacidil, which open the K ATP channel, results in vasodilatation (6). In skeletal muscle, the function of the K ATP channel is less well defined, but it may also be responsible for protection against ischemic damage (10).…”