Isolated rat hearts were subjected to increasing periods of ischemia and reperfusion for examining the changes in the extent of myocardial IR injury and the level of non-enzymatic antioxidants (VC, VE and GSH). Hearts subjected to prolonged period (40 min) of ischemia followed by reperfusion were inflicted with sustainable tissue damage, which was indicated by the increased extent of LDH leakage measured in the coronary effluent....[ Read more ]

Isolated rat hearts were subjected to increasing periods of ischemia and reperfusion for examining the changes in the extent of myocardial IR injury and the level of non-enzymatic antioxidants (VC, VE and GSH). Hearts subjected to prolonged period (40 min) of ischemia followed by reperfusion were inflicted with sustainable tissue damage, which was indicated by the increased extent of LDH leakage measured in the coronary effluent.

Hearts subjected to IR challenge resulted in a marked decrease in tissue VC level, but myocardial VE and GSH level remained relatively unchanged, except under a more severe IR condition. These results suggest that myocardial VC appeared to be first line of antioxidant defense against IR-induced oxidative stress, with myocardial VE served as the ultimate antioxidant defense.

Pretreatment with Sch B and α-lipoic acid (LA) produced the cardioprotective effect on IR-induced injury to various degrees. Although both Sch B and LA pretreatment could suppress the IR-induced LDH leakage, the effect of LA seemed to be more potent. However, while Sch B pretreatment improved the extent of contractile force recovery of the ischemic-reperfused myocardium, no effect was produced by LA pretreatment. The cardioprotection afforded by Sch B pretreatment was associated with increases in myocardial VC and VE levels, with the effect on VE being more prominent. In contrast, the cardioprotective action of LA pretreatment was found to be associated with elevations in myocardial VC and VE level, but the effect on tissue VC level appeared to be much more dramatic.

Hearts isolated from short-term (2-week) diabetic rats were more resistant to IR injury induced by ischemia followed by 20-min of reperfusion. However, this protective effect observable in diabetic hearts diminished or disappeared with the prolongation in reperfusion time from 20 to 40 min, which was corroborated by the decreased in contractile force recovery.

Differential changes in non-enzymatic antioxidant levels were observed in the diabetic myocardium upon IR challenges. The exposure to oxidative stress arising from the diabetic state may play an important role in priming the myocardium in responding to oxidative challenge. However, prolongation in ischemic and reperfusion period could overcome this preconditioned effect, indicated by the drastic increase in LDH leakage and decrease in contractile force recovery.

The diabetic-associated changes in hearts subjected to IR challenge were partially reversed by insulin treatment, but not Sch B. The inability of Sch B pretreatment to protect against IR injury in diabetic hearts suggests the involvement of a common antioxidant mechanism in the cardioprotection afforded by Sch B and diabetic state. Sch B pretreatment could slightly protect against IR injury in insulin-treated diabetic hearts, and the result suggests that Sch B pretreatment may produce beneficial effect on myocardial non-enzymatic antioxidants in insulin-treated diabetic rats under oxidative stress condition.