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Am J Physiol Heart Circ Physiol 284: H927-H930, 2003. First published December 5, 2002; doi:10.1152/ajpheart.00374.2002
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Vol. 284, Issue 3, H927-H930, March 2003

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

Sergej Belosjorow1, Ines Bolle2, Alexej Duschin1, Gerd Heusch1, and Rainer Schulz1

1 Institut für Pathophysiologie, Zentrum für Innere Medizin and 2 Zentrales Tierlabor des Universitätsklinikums Essen, 45122 Essen, Federal Republic of Germany

Pretreatment with tumor necrosis factor-alpha (TNF-alpha ) antibodies abolishes myocardial infarct size reduction by late ischemic preconditioning (IP). Whether or not TNF-alpha 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-alpha 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-alpha 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-alpha concentration during ischemia and infarct size correlated in all groups (r = 0.76). IP, TNF-alpha antibodies, and the combined approach reduced infarct size to a comparable extent. Therefore, the question of whether or not TNF-alpha is causally involved in the infarct size reduction by IP in rabbits could not be answered.

myocardial infarction; ischemic preconditioning; tumor necrosis factor-alpha ; tumor necrosis factor-alpha antibodies


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