Ischemic preconditioning: triggering role of nitric oxide-derived oxidants in isolated hearts

There is evidence that oxidants generated during ischemic preconditioning (IPC) trigger or mediate cardioprotection. We examined whether a causal relationship exists between oxidant formation during ischemic preconditioning and cardioprotection. We monitored formation of dityrosine in crystalloid-perfused guinea pig isolated hearts after a preconditioning protocol and after prolonged ischemia. Superoxide dismutase, catalase, and glutathione (SCG), or the L-arginine analogue NGnitro L-arginine methyl ester (L-NAME) were given during preconditioning. Dityrosine was observed in the coronary effluent immediately after both stimuli, but not after bracketing with SCG or L-NAME. After prolonged ischemia, dityrosine was significantly lower in the IPC group than in other groups. IPC was evidenced by improved mechanical and metabolic function on reperfusion, and by reduced infarction. These effects were abrogated by either SCG or L-NAME. These data support the hypothesis that the formation of nitric oxide-derived oxidants during ischemic preconditioning is causally related to myocardial adaptation to reperfusion injury.