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Am J Physiol Heart Circ Physiol 277: H2470-H2475, 1999;
0363-6135/99 $5.00
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Vol. 277, Issue 6, H2470-H2475, December 1999

SPECIAL TOPIC
Endotoxin and ischemic preconditioning: TNF-alpha concentration and myocardial infarct development in rabbits

Sergej Belosjorow1, Rainer Schulz1, Hilmar Dörge1, F. Ulrich Schade2, and Gerd Heusch1

1 Pathophysiologie and Klinische Forschergruppe Schock und 2 Multiorganversagen, Zentrum für Innere Medizin and Zentrum für Chirurgie des Universitätsklinikums Essen, 45122 Essen, Germany

Ischemic preconditioning (IP) and prior exposure to lipopolysaccharides (LPS) reduce infarct size (IS) and serum tumor necrosis factor-alpha (TNF-alpha ) concentration resulting from myocardial ischemia-reperfusion in rabbits. The decrease in TNF-alpha might relate to an induced TNF-alpha inhibitory serum activity (TNF-alpha -ISA). We analyzed TNF-alpha and TNF-alpha -ISA during 30 and 180 min ischemia and reperfusion, respectively, in anesthetized rabbits either untreated (group 1, n = 7), preconditioned (5 and 10 min ischemia and reperfusion, respectively, group 2, n = 9), or exposed to LPS 72 h before ischemia (group 3, n = 9). TNF-alpha -ISA was assessed by coincubating LPS-stimulated rabbit blood with serum of groups 1-3 and measuring TNF-alpha (WEHI assay). With a comparable area at risk, IS in group 1 was 36.9 ± 11.1 (SD)%, and it was reduced to 13.1 ± 11.6% and 17.3 ± 11.3% (both P < 0.05) in groups 2 and 3, respectively. TNF-alpha was increased during ischemia-reperfusion in group 1 but remained unchanged in rabbits subjected to IP or LPS. TNF-alpha -ISA was detected during ischemia-reperfusion in group 2 (29% and 38% of maximum inhibition, respectively) and during baseline, ischemia and reperfusion in group 3 (51%, 46%, 48% of maximum inhibition, respectively) but was absent in group 1. Cardioprotection by IP and LPS is associated with a reduced TNF-alpha and an induced TNF-alpha -ISA during ischemia-reperfusion.

ischemic preconditioning; tumor necrosis factor-alpha


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