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

Objectives: Tumor necrosis factor (TNF)-alpha is known to be a proinflammatory cytokine that has a pronounced negative inotropic effect and play's 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-alpha by, isolated rat hearts after I 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,.