A palyazatban vegzett munka a kardiovaszkularis sebeszeti beavatkozasok soran kialakulo iszkemias-reperfuzios karosodasok csokkentesenek, kivedesenek lehetősegeit vizsgalja. Munkank soran in vitro miokardium sejttenyeszetben vizsgaltuk az iszkemias pre- es posztkondicionalas szignalmechanizmusaiban az NFkB, az urocortin es a hemoxigenaz-1 szerepet. In vivo allatkiserletes vizsgalataink soran aortakirekesztest kovetően alkalmazott posztkondicionalas citoprotektiv hatasat figyeltuk meg, mely jelentősen csokkentette a kialakulo oxidativ stressz merteket, es mersekelte a lokalis es szisztemas gyulladasos valaszreakciokat, valamint szignifikansan gatolta a proapoptotikus szignalokat. Klinikai vizsgalataink soran leirtuk az akut vegtag iszkemiat kovető reperfuzios folyamatok sejtszintű valtozasait, igazoltuk a posztkondicionalassal kivalthato sejt es szoveti vedelem hatekonysagat. Vizsgalataink hozzajarultak a reperfuzios folyamatok melyebb megismeresehez, valamint sikerult igazolnunk a pre-es posztkondicionalas hatekonysagat kiserletes es klinikai korulmenyek kozott. | In this project we have examined the possible methods for reducing the ischaemic-reperfusion injuries evoked by the cardiovascular surgical interventions. The roles of NFkB, urocortin and haemoxigenase-1 were determined in the signaling pathways of ischaemic pe-and postconditioning in in vitro myocardial cell culture models. In our in vivo animal models we have demonstrated the citoprotective effect of postconditioning after aortic clamping, which could effectively reduce the evoked oxidative stress and systemic and local inflammatory responses. Furthermore postconditioning significantly inhibited the proapoptotic pathways after aortic ischaemia-reperfusion. The pathophysiologic and cellular changes of reperfusion injury in acute limb ischaemia were monitored in our clinical stud. We have confirmed the clinical effectiveness of postconditioning induced citoprotection. Our results help to understand the clinical complications of reperfusion injury and we could evidence the protective potential of pre and postconditioning.

The aim of this study was to investigate the protective effect of urocortin and ischaemic postconditioning against ischaemic reperfusion injury on cultured cardiomyocytes. Isolated neonatal rat ventricular myocytes were divided into 4 groups. Cells were exposed to 30 min ischaemia followed by ischaemic postconditioning (group 1) or urocortin treatment for 10 min (group 2) before the 2 h recovery period in normal cell culture medium. In ischaemic group (group 3) cells underwent only 30 min ischaemia and 2 h recovery. In control group (group 4) cardiac myocytes were incubated in normal cell culture medium. For detecting the cellular injury LDH release, trypan blue staining and ratio of apoptosis/necrosis were examined. Our results show, that LDH content of culture medium, number of trypan blue stained dead cells and the rate of apoptotic and necrotized cells was decreased in both ischaemic postconditioned and urocortin treated compared with ischaemic group. We can conclude that urocortin induced such an efficient cell protective effect as ischaemic postconditioning. Furthermore, urocortin might be also used as a pharmacological postconditioning agent after a prolonged hypoxic stimulus against ischaemic cell injury. Supported by OTKA T-048851; ETT 168/2006; OTKA T-060227 grants.

Urocortin, member of CRF peptides has potent effects on the cardiovascular system inducing protection against ischaemia/reperfusion injury. The aim of this study was to investigate the action of urocortin on cultured cardiomyocytes in the process of pre- and postconditioning.

Cold preservation prior to small-bowel transplantation can moderate tissue injury, although it is unable to protect the bowel graft from acute reperfusion injury. One method to reduce oxidative stress is ischemic preconditioning (IPC). The limited data regarding IPC of the bowel encouraged us to investigate the key factor in this process, i.e., the activation of nuclear factor-kappa binding (NF-kB) in bowel tissue. The intestine was preconditioned by various cycles of IPC on rats. Activation of NF-kB was detected by a chemiluminescence-based ELISA method. Our findings showed that NkB level was elevated significantly 30 min after IPC. One hour following IPC, NF-kB decreased to control level; 2 In after IPC, the level significantly increased again. These changes were independent of the number of IPC cycles. Our experiments with various IPC cycles revealed that even a very short IPC cycle was able to activate the IPC cascade in small-bowel tissue. (c) 2006 Wiley-Liss, Inc.