The involvement of cytokines in the second window of ischaemic preconditioning

1 We utilized a rat model of myocardial infarction to investigate whether manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, and tumour necrosis factor- alpha (TNF-alpha) and/or interleukin-1 beta (IL-1 beta) are involved in the late phase of ischaemic preconditioning (IP). 2 IP was induced in anaesthetized rats by four 3-min left coronary artery (LCA) occlusions, each separated by 10 min of reperfusion. Twenty-four hours after the repetitive brief ischaemia, the LCA was occluded for 20 min followed by reperfusion for 48 h. IP reduced the infarct size by approximately 46% as determined after 48 h of reperfusion. 3 Antisense oligodeoxynucleotides to Mn-SOD inhibited the increases in Mn-SOD content and activity, and abolished the expected decrease in myocardial infarct size. Sense or scrambled oligodeoxynucleotides did not abolish either Mn-SOD induction or tolerance to ischaemia/reperfusion. 4 The simultaneous administration of the antibodies to TNF-alpha (0.5 ml) and IL-I beta (0.5 mg) prior to IP abolished the cardioprotection and the increase in Mn-SOD activity induced by IF. 5 We conclude that the induction and activation of PI ln-SOD, mediated by TNF-alpha and IL-I beta after IP, plays an important role in the acquisition of late-phase cardioprotection against ischaemia/reperfusion injury in rats.