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

Abstract

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.