Optimierung der Organprotektion durch Modulation des Ischämie‑/Reperfusionsschadens in der Herzchirurgie

Up to the present day it has still not been clarified what role the so-called ischemia-reperfusion injury (I‑R injury) plays in systemic inflammation in cardiac surgery patients. So far there is no causal prophylaxis or treatment to avoid or at least attenuate I‑R injury and its sequelae. During the postperfusion syndrome mediated by the extracorporeal circulation (ECC), I‑R injury is a relevant problem in any case, whereby it is still not clarified whether it is the result of a causal function or due to inflammation. To investigate this question a small animal ECC model for rats was developed in order to trigger I‑R injury after establishment of deep hypothermic cardiac arrest. In numerous sub-analyses various substances with potential anti-inflammatory characteristics were employed to weaken or even to block the pathomechanism of the systemic inflammatory reaction at different stages. It could be shown that in animal experiments the trace element selenium can reduce the I‑R injury after cardiac arrest. In these experiments a preventive administration of everolimus led to a reduction of the release of inflammatory cytokines by inhibition of the mammalian target of rapamycin (mTOR) signal pathway. The administration of the calcium sensitizing agent levosimendan influenced the secretion of cytokines and apoptosis. Rats that received preoperative levosimendan recovered faster from the sequelae of the cardiac arrest. In the Clinic for Cardiac Surgery of the Heinrich Heine University Düsseldorf levosimendan is also regularly used in patients with impaired pump function after heart transplantation and leads to a significant reduction in mortality, especially when used in a timely fashion. Further studies are needed to show if this positive effect is the result of the modulation of I‑R injury.