Sevoflurane exposure generates superoxide but leads to decreased superoxide during ischemia and reperfusion in isolated hearts

Reactive oxygen species (ROS) are largely responsible for cardiac injury consequent to ischemia and reperfusion, but, paradoxically, there is evidence suggesting that anesthetics induce preconditioning (APC) by generating ROS. We hypothesized that sevoflurane generates the ROS superoxide (O-s(.-)), that APC attenuates O-2(.-) formation during ischemia, and that this attenuation is reversed by bracketing APC with the O-2(.-) scavenger manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the putative mitochondrial adenosine triphosphate-sensitive potassium (mK(ATP)) channel blocker 5-hydroxydecanoate (5-HD). O-2(.-) was measured continuously in guinea pig hearts by using dihydroethidium. Sevoflurane was administered alone (APC), with MnTBAP, or with 5-HD before 30 min of ischemia and 120 min of reperfusion. Control hearts underwent no pretreatment. Sevoflurane directly increased O-2(.-); this was blocked by MnTBAP but not by 5-HD. O-2(.-) increased during ischemia and during reperfusion. These increases in O-2.- were attenuated in the APC group, but this was prevented by MnTBAP or 5-HD. We conclude that sevoflurane directly induces O-2(.-) formation but that O-2(.-) formation is decreased during subsequent ischemia and reperfusion. The former effect appears independent of mK(ATP) channels, but not the latter. Our study indicates that APC is initiated by ROS that in turn cause mK(ATP) channel opening. Although there appears to be a paradoxical role for ROS in triggering and mediating APC, a possible mechanism is offered.