Heparin added to cardioplegic solution inhibits tumor necrosis factor-α production and attenuates myocardial ischemic-reperfusion injury

Dimitry Pevni, Inna Frolkis*, Itzhak Shapira, Doron Schwartz, Yael Yuhas, Idit F. Schwartz, Tamara Chernichovski, Gideon Uretzky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Tumor necrosis factor (TNF)-α is known to be a proinflammatory cytokine that has a pronounced negative inotropic effect and plays an important role in ischemic-reperfusion injury. Methods: Twenty isolated rat hearts were randomly divided equally into two groups (heparin and nonheparin) and were perfused with a Krebs-Henseleit solution using a modified Langendorff model. The influence of heparin on the synthesis and release of TNF-α by isolated rat hearts after 1 h of global cardioplegic ischemia and on left ventricular (LV) performances during 30 min of postischemic reperfusion was investigated. Results: Significant mean (± SEM) amounts of TNF-α in myocardial tissue (1,149 ± 33.7 pg/g) and effluent (951.8 ± 27.3 pg/mL) from the coronary sinus were detected after global cardioplegic ischemia. The addition of heparin to the cardioplegic solution significantly improved the recovery of LV function in the postischemic heart (p < 0.0001 for all measurements). TNF-α protein production in the heparin-treated hearts was below detectable levels despite a postischemic increase of TNF-α messenger RNA expression in both heparin-treated hearts and non-treated hearts (0.71 ± 0.06 and 0.8 ± 0.12 relative optical density, respectively). Conclusion: This study shows, for the first time, that heparin causes the inhibition of TNF-α protein synthesis and release from the isolated ischemic rat heart within the posttranscriptional stage, and that it prevents the depression of LV function caused by ischemic-reperfusion injury.

Original languageEnglish
Pages (from-to)1805-1811
Number of pages7
JournalChest
Volume128
Issue number3
DOIs
StatePublished - Sep 2005

Keywords

  • Cardioplegia
  • Isolated perfused heart
  • Messenger RNA
  • Tumor necrosis factor-α

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