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 (KATP) channels, and cellular location of the channels. Neonatal New Zealand White rabbits at 7-10 days of age (n ϭ 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 Ϯ SD) by 50% (10 Ϯ 5%) versus untreated controls (20 Ϯ 6%). Isoflurane increased recovery of preischemic left ventricular developed pressure by 28% (69 Ϯ 4%) versus untreated controls (54 Ϯ 6%). The mitochondrial KATP channel blocker 5-hydroxydecanoate (5-HD) completely (55 Ϯ 3%) and the sarcolemmal KATP channel blocker HMR 1098 partially (62 Ϯ 3%) attenuated the cardioprotective effects of isoflurane. The combination of 5-HD and HMR-1098 completely abolished the cardioprotective effect of isoflurane (56 Ϯ 5%). We conclude that both mitochondrial and sarcolemmal KATP channels contribute to isoflurane-induced delayed cardioprotection. ischemia; heart; infarct size; volatile anesthetics; myocardial preconditioning BRIEF PERIODS OF ISCHEMIA lead to a reduced severity of cardiac injury following a second sustained period of ischemia. This cardioprotective effect has been termed ischemic preconditioning and has been demonstrated in all species studied. Certain pharmacological agents can mimic the cardioprotective effect of ischemic preconditioning. Recent clinical and experimental data indicate that volatile anesthetics also exert acute protective effects on the myocardium.The protective effects of volatile anesthetics on ischemic myocardium have been termed anesthetic-induced preconditioning because of its remarkable similarity to ischemic preconditioning. Isoflurane improves functional recovery of stunned myocardium in chronically or acutely instrumented dogs after brief periods of coronary artery occlusion and reperfusion (25,26,44). Low doses of the ATP-sensitive K (K ATP ) channel blocker glibenclamide completely abolished the cardioprotective effects of isoflurane (25). These results indicate that K ATP channels are activated by isoflurane and mediate the beneficial effects of isoflurane in stunned myocardium in animal models that respond to acute ischemic preconditioning in a similar fashion to the human heart (5, 45).K ATP channel openers mimic early ischemic preconditioning, whereas K ATP channel blockers prevent ischemic preconditioning. These effects were initially attributed to opening and closing of sarcolemmal K ATP channels, respectively. New evidence suggests, however, that mitochondrial K ATP channels might very well have even a greater influence on preconditioning (35, 37). For instance, diazoxide, an opener of mitochondrial K ATP channels, was demonstrated to exert ca...

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized polyphenols might potentiate DR-induced lifespan extension. Twenty week old C57BL/6 mice were placed on one of three diets: continuous feeding (control), alternate day chow (Intermittent fed, IF), or IF supplemented with polyphenol antioxidants (PAO) from blueberry, pomegranate, and green tea extracts (IF+PAO). Both IF and IF+PAO groups outlived the control group and the IF+ PAO group outlived the IF group (all p < 0.001). In the brain, IF induced the expression of inflammatory genes and p38 MAPK phosphorylation, while the addition of PAO reduced brain inflammatory gene expression and p38 MAPK phosphorylation. Our data indicate that while IF overall promotes longevity, some aspects of IF-induced stress may paradoxically lessen this effect. Polyphenol compounds, in turn, may potentiate IF-induced longevity by minimizing specific components of IF-induced cell stress.