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


CONCLUSIONS
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.
Pevni
Dimitry
D
Department of Thoracic and Cardiovascular Surgery, Tel Aviv Sourasky Medical Center, 6 Weizmann St, Tel Aviv 64239, Israel.
Frolkis
Inna
I
Shapira
Itzhak
I
Schwartz
Doron
D
Yuhas
Yael
Y
Schwartz
Idit F
IF
Chernichovski
Tamara
T
Uretzky
Gideon
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000893:Anti-Inflammatory Agents; D002314:Cardioplegic Solutions; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin