One of the major reasons for divergence in I R induced signalling events may be the extent 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 selleck chem inhibitor an explanation for the differ ences between our results and those Inhibitors,Modulators,Libraries of other studies. In contrast, abnormal calcium levels can be excluded in our set up as a trigger for kinase activation and heat shock protein induction, because no difference was no ticed in calcium serum levels. In the presented work we have chosen to undertake a final measurement Inhibitors,Modulators,Libraries of protein expression and phosphor ylation at the end of the complete I R procedure.

Al though this approach has proven valid to demonstrate various aspects of an ideal SIRS I R model, it yet may have led to a simplified picture of events occurring over the time period of the entire experiment. Likewise, the one point detection of the read out measures may have caused a systematic masking of kinase phosphorylation kinetics that are known to Inhibitors,Modulators,Libraries represent a highly time dependent transi ent effect. Furthermore, the truly SIRS dependent molecular effects have to be dissected from other I R vari ables by ongoing experiments. Thus, in following studies the influence of hypothermia, reperfusion and haemolysis on I R and SIRS triggered signalling events shall be further analysed. The following limitations may be applied to our study. Cardiac arrest was achieved by deep hypothermia, no cardioplegic solution was applied.

This was done on pur pose to exclude signalling induced by excessive applica tion of potassium. Since the focus of the study centers on early signalling events which may Inhibitors,Modulators,Libraries protect from or in duce organ damage, we did not investigate angiopathic and apoptotic Inhibitors,Modulators,Libraries changes induced by I R. Moreover the transition from SIRS to MODS was not aim of this study. These points will be considered in ongoing studies. Conclusion We established a CPB rat model that can reproduce com mon pathophysiological and molecular alterations that are associated with the induction of SIRS and the activation of specific signalling cascades. This standardised model may serve http://www.selleckchem.com/products/DAPT-GSI-IX.html as a tool to evaluate the extent of the inflammatory reactions and organ damage associated with I R and SIRS and to investigate the potential of novel therapeutics in a preclinical model. It might be suitable to test the efficacy of immunosuppressive therapeutics applied in major heart surgery using CPB with and without DHCA. The contri bution of the different aspects of CPB might be investi gated in detail, as the role of oxidative stress and inflammation might be further discriminated by ana lysing the involved molecular pathways.