1 We utilized a rat model of myocardial infarction to investigate whether m
anganese 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 I
P was induced in anaesthetized rats by four 3-min left coronary artery (LCA
) occlusions, each separated by 10 min of reperfusion. Twenty-four hours af
ter the repetitive brief ischaemia, the LCA was occluded for 20 min followe
d 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-S
OD content and activity, and abolished the expected decrease in myocardial
infarct size. Sense or scrambled oligodeoxynucleotides did not abolish eith
er Mn-SOD induction or tolerance to ischaemia/reperfusion.
4 The simultaneous administration of the antibodies to TNF-alpha (0.5 ml) a
nd IL-I beta (0.5 mg) prior to IP abolished the cardioprotection and the in
crease in Mn-SOD activity induced by IF.
5 We conclude that the induction and activation of PI ln-SOD, mediated by T
NF-alpha and IL-I beta after IP, plays an important role in the acquisition
of late-phase cardioprotection against ischaemia/reperfusion injury in rat
s.