Delayed cardioprotection by isoflurane: role of K ATP channels

Isoflurane mimics the cardioprotective effect of acute ischemic preconditioning with an acute memory phase. We determined whether isoflurane can induce delayed cardioprotection, the involvement of ATP-sensitive potassium (K ATP ) channels, and cellular location of the channels. Neonatal New Zealand White rabbits at 7–10 days of age ( n = 5–16/group) were exposed to 1% isoflurane-100% oxygen for 2 h. Hearts exposed 2 h to 100% oxygen served as untreated controls. Twenty-four hours later resistance to myocardial ischemia was determined using an isolated perfused heart model. Isoflurane significantly reduced infarct size/area at risk (means ± SD) by 50% (10 ± 5%) versus untreated controls (20 ± 6%). Isoflurane increased recovery of preischemic left ventricular developed pressure by 28% (69 ± 4%) versus untreated controls (54 ± 6%). The mitochondrial K ATP channel blocker 5-hydroxydecanoate (5-HD) completely (55 ± 3%) and the sarcolemmal K ATP channel blocker HMR 1098 partially (62 ± 3%) attenuated the cardioprotective effects of isoflurane. The combination of 5-HD and HMR-1098 completely abolished the cardioprotective effect of isoflurane (56 ± 5%). We conclude that both mitochondrial and sarcolemmal K ATP channels contribute to isoflurane-induced delayed cardioprotection.