Induction of the haem oxygenase gene expression during the reperfusion of ischemic rat myocardium.

A variety of stress including oxidative stress, hyperthermia and heavy metals can induce the expression of haem oxygenase in mammalian tissue. In this study we examined whether an ischemic stress could induce haem oxygenase in heart. Isolated perfused rat hearts were subjected to either 5 or 20 min of ischemia followed by 15, 30, 45 and 60 min of reperfusion in each case. The results of our study indicate that haem oxygenase is not induced by ischemia, but can be induced by reperfusion. The induction of haem oxygenase is a function of the duration of reperfusion. This induction can be blocked by pre-perfusing the hearts with oxygen free radical scavengers, superoxide dismutase (SOD) and catalase. Haem oxygenase was also induced in the hearts by perfusing them with oxygen free radical generating system. This induction was also blocked by SOD and catalase. Immunohistochemical localization revealed that haem oxygenase-1 is primarily accumulated in the perivascular region and in the cardiomyocytes. This suggests that it is oxygen free radicals that is produced during the reperfusion is the stimulus for the expression of haem oxygenase in the ischemic/reperfused myocardium.