TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

Abstract

Pretreatment with tumor necrosis factor-α (TNF-α) antibodies abolishes myocardial infarct size reduction by late ischemic preconditioning (IP). Whether or not TNF-α is also important for myocardial infarct size reduction by classic IP is unknown. Anesthetized rabbits were untreated ( group 1, n = 7), classically preconditioned by 5 min left coronary artery occlusion/10 min reperfusion ( group 2, n = 6), or pretreated with TNF-α antibodies without ( group 3, n = 6) or with IP ( group 4, n = 6) before undergoing 30 min of occlusion and 180 min of reperfusion. Infarct size in group 1 was 44 ± 11 (means ± SD)% of the area at risk. With a comparable area at risk, infarct size was reduced to 13 ± 7%, 23 ± 8%, and 19 ± 12% (all P < 0.05) in groups 2, 3, and 4, respectively. The circulating TNF-α concentration was increased during ischemia in group 1 from 752 ± 403 to 1,542 ± 482 U/ml ( P < 0.05) but remained unchanged in all other groups. Circulating TNF-α concentration during ischemia and infarct size correlated in all groups ( r = 0.76). IP, TNF-α antibodies, and the combined approach reduced infarct size to a comparable extent. Therefore, the question of whether or not TNF-α is causally involved in the infarct size reduction by IP in rabbits could not be answered.