The observed alterations of most of the analysed blood parameters showed, that they underlie an influence by CPB. The above mentioned increase in plasma AST ac tivity is expected to occur after reperfusion, as it repre sents a marker table 1 for liver, skeletal and cardiac muscle damage. The observed decrease in AST activity during Inhibitors,Modulators,Libraries the cooling period might be due to haemodilution asso ciated with CPB. Although the increase of creatinine remained within the reference range, the course of this parameter indi cates an impaired renal function developing throughout the experiment, possibly caused by I R induced renal tis sue damage as reported. The increased levels of cardiac troponin, CK MB and LDH were in accordance with findings 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 Inhibitors,Modulators,Libraries 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 Inhibitors,Modulators,Libraries 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 Inhibitors,Modulators,Libraries 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 expression patterns of stress pro Inhibitors,Modulators,Libraries teins could be detected. As assessed by STAT3 phos phorylation, an inflammatory response was observed in all organs as expected. 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 experiments and based on literature a number of I R induced alternations of the protein expression 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 expected changes were not entirely confirmed by the presented experiments. 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 then for the heart as opposed to other or gans.