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


Zhang M., Xu Y., Saini H. K., TURAN B., Liu P. P., Dhalla N. S.

American Journal of Physiology - Heart and Circulatory Physiology, vol.289, no.2 58-2, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 289 Issue: 2 58-2
  • Publication Date: 2005
  • Doi Number: 10.1152/ajpheart.00178.2005
  • Journal Name: American Journal of Physiology - Heart and Circulatory Physiology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: tumor necrosis factor, nuclear factor-kappa B, heart failure, cardiomyopathy, ischemia, reperfusion, NECROSIS-FACTOR-ALPHA, NF-KAPPA-B, PROINFLAMMATORY CYTOKINES, INJURY, INVOLVEMENT, EXPRESSION, MUSCLE, CELLS, PERFORMANCE, INHIBITION
  • Lokman Hekim University Affiliated: No

Abstract

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)-α in myocardium and PTXF has been shown to depress the production of TNF-α in failing heart, this study examined the hypothesis that PTXF may attenuate cardiac dysfunction and reduce TNF-α 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-α, nuclear factor-κB (NF-κB), and phosphorylated NF-κB contents were decreased in ischemic heart but were markedly increased within 2 min of starting reperfusion. The ratio of cytosolic-to-homogenate NF-κB was decreased, whereas the ratio of particulate-to-homogenate NF-κB was increased in I/R hearts. These changes in TNF-α and NF-κB protein contents as well as in NF-κB 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-κB and the production of TNF-α content. Copyright © 2005 the American Physiological Society.