Neutrophils contribute to TNF induced myocardial tolerance to ischaemia.
Sublethal endotoxin (ETX) pretreatment of rats induces protection from cardiac ischaemia-reperfusion injury. This protective state is associated with increased endogenous myocardial catalase activity. Since tumour necrosis factor (TNF) is one mediator of ETX effects, we hypothesized that (TNF) pretreatment of the rat (30 micrograms/kg ip) 36 h prior to cardiac ischaemia-reperfusion could induce myocardial protection. We found that TNF administration increased both myocardial tolerance to ischaemia reperfusion injury (modified Langendorff, buffer perfusion, global, normothermic ischaemia) and myocardial catalase activity at 36 h. Moreover, we found that 6 h after TNF administration, myocardial hydrogen peroxide (H2O2, assessed by aminotriazole-H2O2 inactivation of catalase) and myocardial neutrophil accumulation (assessed by histology) were both increased. When neutrophil function was inhibited either by neutrophil depletion (vinblastine) or by ibuprofen treatments of the rat before TNF, the protection previously apparent at 36 h was blocked. We conclude that TNF can induce myocardial resistance to ischaemia reperfusion injury. This protection is related to prior tissue neutrophil accumulation and concomitant increases in H2O2 levels.
Brown
J M
JM
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Anderson
B O
BO
Repine
J E
JE
Shanley
P F
PF
White
C W
CW
Grosso
M A
MA
Banerjee
A
A
Bensard
D D
DD
Harken
A H
AH
D000818:Animals; D002374:Catalase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D014747:Vinblastine; D006861:Hydrogen Peroxide; D002374:Catalase; D007052:Ibuprofen