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This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/H832    most recent 00178.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Zhang, M. Articles by Dhalla, N. S. Search for Related Content PubMed PubMed Citation Articles by Zhang, M. Articles by Dhalla, N. S.

Pentoxifylline attenuates cardiac dysfunction and reduces TNF- level in ischemic-reperfused heart

¹Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg; and ²Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada

Submitted 22 February 2005 ; accepted in final form 12 April 2005

Although pentoxifylline (PTXF), a phosphodiesterase inhibitor, has been reported to exert beneficial effects in cardiac bypass surgery, its effect and mechanisms against ischemia-reperfusion (I/R) injury in heart are poorly understood. Because I/R is known to increase the level of tumor necrosis factor (TNF)- in myocardium and PTXF has been shown to depress the production of TNF- in failing heart, this study examined the hypothesis that PTXF may attenuate cardiac dysfunction and reduce TNF- content in I/R heart. For this purpose, isolated rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 2–30 min. Although cardiac dysfunction due to ischemia was not affected, the recovery of heart function upon reperfusion was markedly improved by PTXF treatment. This cardioprotective effect of PTXF was dose dependent; maximal effect was seen at a concentration of 125 µM. TNF-, nuclear factor-B (NF-B), and phosphorylated NF-B contents were decreased in ischemic heart but were markedly increased within 2 min of starting reperfusion. The ratio of cytosolic-to-homogenate NF-B was decreased, whereas the ratio of particulate-to-homogenate NF-B was increased in I/R hearts. These changes in TNF- and NF-B protein contents as well as in NF-B redistribution due to I/R were significantly attenuated by PTXF treatment. The results of this study indicate that the cardioprotective effects of PTXF against I/R injury may be due to reductions in the activation of NF-B and the production of TNF- content.

tumor necrosis factor; nuclear factor-B; heart failure; cardiomyopathy; ischemia; reperfusion

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