Mitochondrial superoxide production and respiratory activity: biphasic response to ischemic duration

Long bouts of ischemia are associated with electron transport chain deficits and increases in free radical production. In contrast, little is known regarding the effect of brief ischemia on mitochondrial function and free radical production. This study was undertaken to examine the relationship between the duration of ischemia, effects upon electron transport chain activities, and the mitochondrial production of free radicals. Rat hearts were subjected to increasing ischemic durations, mitochondria were isolated, and superoxide production and electron transport chain activities were measured. Results indicate that even brief ischemic durations induced a significant increase in superoxide production. This rate was maintained with ischemic durations less than 15 min, and then increased further with longer ischemic times. Mechanistically, brief ischemia was accompanied by an increase in NADH oxidase activity, reflected by a specific increase in complex IV activity. In contrast, longer ischemic durations were accompanied by a decrease in NADH oxidase activity, reflected by deficits in complexes I and IV activities.