Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate andgadolinium - Possible involvement of mitochondrial adenosine triphosphate-sensitive potassium and stretch-activated channels

Background: Both mitochondrial adenosine triphosphate-sensitive potassium ( MKATP) channels (selectively blocked by 5-hydroxydecanoate) and stretch-act ivated channels (blocked by gadolinium) have been Involved in the mechanism of ischemic preconditioning, Isoflurane can reproduce the protection affor ded by ischemic preconditioning, We sought to determine whether isoflurane- induced preconditioning may involve MKATP and stretch-activated channels. Methods: Anesthetized open-chest rabbits underwent 30 min of coronary occlu sion followed by 3 h of reperfusion, Before this, rabbits were randomized i nto one of six groups and underwent a treatment period consisting of either no intervention for 40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal) followed by a 15-min washout period (isoflurane group; n = 9). The two groups received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or gadolinium (40 mu mol/kg) before coronary occlusion and reperfusion (5-hydroxydecanoate n = 9; gadolinium, n = 7), Tw o additional groups received 5-hydroxydecanoate or gadolinium before isoflu rane exposure (isoflurane-5-hydroxydecanoate, n = 10; isoflurane-gadolinium , n = 8). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. Results: Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27 +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in th e control, isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, i soflurane-gadolinium, and gadolinium groups, respectively). Infarct size av eraged 60 +/- 20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15 % of the risk zone in 5-hydroxydecanoate- and gadolinium-treated controls ( P = nonsignificant), in contrast, Infarct size in the isoflurane group was significantly reduced to 26 +/- 11% of the risk zone (P < 0.05 vs. control) . Both 5-hydroxydecanoate and gadolinium prevented this attenuation: infarc t size averaged 68 +/- 23 and 56 +/- 21% of risk zone in the isoflurane-5-h ydroxydecanoate and isoflurane-gadolinium groups, respectively (P = nonsign ificant vs. control). Conclusion: 5-Hydroxydecanoate and gadolinium inhibited pharmacologic preco nditioning by Isoflurane. This result suggests that MKATP channels and mech anogated channels are probably involved in this protective mechanism.