The increased levels of cardiac troponin, CK MB and LDH were in accordance with findings nearly of other groups and have been reported in humans after CPB and I R, re spectively as compared to the levels before surgery. The increase of IL 6 and TNF during reperfusion is associated with SIRS and may induce JAK STAT signal ling during CPB. The dramatic increase of IL 6 and TNF after the reperfusion is correlated with a strong leucocytosis. At the same time points CRP levels remained low, matching very well the conditions of a beginning SIRS for the intra operative time frame we decided to in vestigate. CRP as a marker of the complement system ac tivation is elevated only after one or two days after surgery.

The present study could demonstrate that I R in jury as applied in the described model leads to an increase of the pro inflammatory cytokines IL 6 and TNF, which can activate intracellular signalling. For the interpret ation of the above data it must be considered that we ob served haemolysis in the reperfusion blood samples and that haemolysis can cause an increase of LDH, AST, ALT, potassium and CK levels. As a further result of SIRS and I R organ specific phosphorylation and e pression patterns of stress pro teins could be detected. As assessed by STAT3 phos phorylation, an inflammatory response was observed in all organs as e pected. Those findings are in agree ment with the increased number of leucocytes and the higher IL 6 plasma levels in I R animals after reperfu sion.

Previous to the presented e periments and based on literature a number of I R induced alternations of the protein e pression level and protein phosphorylation level were anticipated, particularly involving MAPK acti vation as well as heat shock protein induction. However, following our cardiocentric and clinically derived approach those e pected changes were not entirely confirmed by the presented e periments. The anticipated alterations were not present for all of the detected proteins in all organs. How ever, an organ specific pattern of intracellular response to I R has already been suggested, e. g. demonstrating divergent results for the heart as opposed to other or gans. Especially JNK phosphorylation Batimastat pattern were dissimilar for most organs, but contradictory re sults have been reported, indicating that JNK activa tion may differ in I R injury. One of the major reasons for divergence in I R induced signalling events may be the e tent of I R that actually acts on the indi vidual organs, but also the organ inherent tolerance to transient ischemic periods. In case of the heart, the level of induced cardioplegia as applied in different models may represent an e planation for the differ ences between our results and those Ruxolitinib side effects of other studies.