The involvement of cytokines in the second window of ischaemic preconditioning.
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-1beta (IL-1beta) are involved in the late phase of ischaemic preconditioning (IP). 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. 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. The simultaneous administration of the antibodies to TNF-alpha (0.5 ml) and IL-1beta (0.5 mg) prior to IP abolished the cardioprotection and the increase in Mn-SOD activity induced by IP. We conclude that the induction and activation of Mn-SOD, mediated by TNF-alpha and IL-1beta after IP, plays an important role in the acquisition of late-phase cardioprotection against ischaemia/reperfusion injury in rats.
Yamashita
N
N
The First Department of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hoshida
S
S
Otsu
K
K
Taniguchi
N
N
Kuzuya
T
T
Hori
M
M
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature; D003331:Coronary Vessels; D016207:Cytokines / Q000378:metabolism*; D004790:Enzyme Induction; D006439:Hemodynamics; D019194:Ischemic Preconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000401:mortality; D009206:Myocardium / Q000201:enzymology; D020011:Protective Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000096:biosynthesis; D014693:Ventricular Fibrillation
D016207:Cytokines; D020011:Protective Agents; D013482:Superoxide Dismutase