Chemical preconditioning: A cytoprotective strategy

Abstract

Brief ischemic or hypoxic episodes may increase or decrease tolerance towards subsequent severe ischemia in heart and brain. A similar phenomenon is observed after mild chemical inhibition of oxidative phosphorylation--chemical preconditioning. We have shown that chemical preconditioning can be induced by chemical inhibition of mitochondrial complex I and mitochondrial complex II. With a time interval of three hours between chemical pretreatment and massive inhibition of oxidative phosphorylation, recovery of population spike amplitude in hippocampal region CA1 after stimulation of the Schaffer collaterals was 31 +/- 9% in controls, 98 +/- 14% after i.p. treatment with 1 mg/kg body weight haloperidol, an inhibitor of mitochondrial complex I and 90 +/- 7% with pretreatment with 3-np, an inhibitor of mitochondrial complex II. Activation of ATP regulated potassium channels partakes in mediating the preconditioning effect. We conclude that chemical preconditioning is a practical prophylactic pharmacologic strategy to increase hypoxic tolerance.