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

Chest. 2005 Sep;128(3):1805-11. doi: 10.1378/chest.128.3.1805.

Abstract

Objectives: Tumor necrosis factor (TNF)-alpha 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 non-heparin) and were perfused with a Krebs-Henseleit solution using a modified Langendorff model. The influence of heparin on the synthesis and release of TNF-alpha 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-alpha 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-alpha protein production in the heparin-treated hearts was below detectable levels despite a postischemic increase of TNF-alpha messenger RNA expression in both heparin-treated hearts and nontreated 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-alpha 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.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cardioplegic Solutions / pharmacology*
  • Heart / drug effects*
  • Heart / physiology
  • Heparin / pharmacology*
  • Male
  • Models, Animal
  • Myocardial Reperfusion Injury / prevention & control*
  • Perfusion / methods
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Anti-Inflammatory Agents
  • Cardioplegic Solutions
  • Tumor Necrosis Factor-alpha
  • Heparin