Perioperative Untersuchungen zur antioxidativen Kapazität des Serums von kardiochirugischen Patienten

Postoperative pulmonale Komplikationen nach kardiochirurgischen Eingriffen stellen häufig ein Problem dar. Sie führen zu verlängertem Intensivaufenthalt und tragen zur Entstehung nachfolgender Komplikationen und Organdysfunktionen, bis hin zum Multiorganversagen bei. Die respiratorische Insuffizien...

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Bibliographic Details
Main Author: Sirat, Abdul Sami
Contributors: Vogt, Sebastian (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2009
Online Access:PDF Full Text
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Multiple factors affect pulmonary morbidity after cardiac surgery including cigarette smoking, age, adipositas, surgery-related factors (postoperative pain, dysfunction of the diaphragm), extracorporeal circulation, perioperative respiratory infections as well as side effects of drugs administered. Moreover, open heart surgery induces an inflammatory response. Especially in total cardiopulmonary bypass, the lungs depend on oxygen supply provided by bronchial arterial flow. In case of partial ECC with maintenance of ventilation, less severe pulmonary arterial blood flow deprivation leeds to a reduction in severity of pulmonary injury, because the interrupted blood flow disrupts multiple essential vascular haemostatic mechanisms. Several interacting systems interact in postischemic inflammation and reperfusion injury exist including expression of circulating adhesion molecules and their induction at the endothelial surface, activation of the complement cascade and alterations in anticoagulation defense. Considering the haemostatic changes in the pulmonary vasculature during ECC, the possible involvement of activated leucocytes have been implicated in pathophysiological concepts for the “postpump- syndrom” and ARDS. For example the ECC causes an immediate release of HSP 70 into the circulation and modulates monocyte function by TLR-2 and TLR-4 expression with successive activation of immune responses. The HSP 70- induction may therefore be either protective or enhance injury to myocardial tissue. There is an interference of ischemic response to coronary heart disease and extracorporeal circulation. Detection of anti-HSP 70- antibodies have been shown to correlate with better outcome of patients after CABG- surgery and may play a role in regulation of HSP 70 expression known to protect cardiac tissue from ischemic injury. In accordance with this finding, the detection of these antibodies was directly correlated with a low antioxidative capacity of patient’s sera. Besides surfactant alterations, the lung creates an own stress response scenario, which participates in complex immunological response after extracorporeal circulation. All pathophysiological mechanisms thus far proposed involve release and compensation of free radicals, which are important effectors of tissue injury. Ranking these mechanisms, different authors pronounce a predominant role for the TNFα- IL6-cascade on surgery’s impact, and the importance of oxidative stress exacerbation. A recent paper by Luyten et al. describes a systemic inflammation caused by severe oxidative stress following cardiac surgery. They found both glutathione-peroxidase and superoxide- dismutase increased in their activity although they do not suffice in fully compensating oxidative damage. Therefore, the clinical consequences of a gap in compensation has to be addressed. In our recent study we investigated the antioxidative capacity, including radical bursts (singlet oxygen, peroxynitrite, hydroxylradicals etc.), perioperatively, in the serum of cardiosurgical patients qualified for elective CABG-surgery and focused our interest on respiratory parameters. Until now, there are no exact data available on a possible threshold for AOC findings. Fifty-one patients were involved in this blinded study. We compared parameters of inflammatory response, haemodynamics and pulmonary function between - patients with preoperative “high AOC” and “low AOC”-. The cut off-value was the median of preoperative AOC in the whole sample (0.88 mmol/l). Although there was a deviation in gender within the groups its bias was neglected. We then reinvestigated all the parameters retrospectively and found a difference in inflammatory response. Whereas the cellular component of inflammation is pronounced in the “low-AOC”-group, a higher humoral response is seen in the “high AOC”-group. These data suggest a different augmentation of the preoperative inflammatory status caused by atherosclerosis and refer to a different reaction on cardiosurgical trauma. Therefore it may be useful to enter the “AOC”-parameter into the preoperative diagnostic schedule. Respiratory complications after cardiac surgery are frequent. We evaluated the arterial- alveolar oxygen gradient (AaD02) and the MURRAY-score, which includes artificial ventilation- parameters (PEEP), X-ray findings of the chest (e.g. Dystelectasis, Atelectasis) and airway-blood oxygen tensions, respectively. Indeed, a low preoperative AOC results in a statistically significant lower postoperative AaDO2 – gradient (p < 0.001). Although not significant, the MURRAY- score also reflects this tendency. Both groups had an improvement in postoperative cardiac output, but a clear reduction in pulmonary capillary wedge pressure (PCWP) was only seen in the “high- AOC”-group. Although improvement in cardiac function is surely related to the success in revascularization, altered PCWP- values should also be considered in the context of the endothelial dysfunction. Oxidative stress alters the function of the pulmonary endothelium, especially the modulation of vasomotor tone. Although different enzyme systems contribute to ROS formation and oxidative burden, evidence is accumulating that the initial generation of ROS by NADH-oxidases triggers the release of ROS by other enzymes (e.g. endothelial NO-synthase). In case of extracorporeal circulation a hypoxia- induced ROS- generation in the pulmonary vasculature has to be suggested. Moreover, it seems feasible that initial ROS- induced vasoconstriction is followed by an inflammation- induced relaxation of the endothelium accompanied with a hyporeactivity of the vasculature. Therefore, we found decreased PCWP in both groups. The postoperative reduced PCWP in the “high AOC”- group (p=0.015) may account for a higher “buffer” capacity of blood to released ROS from the pulmonary endothelium and a postulated relaxation . In this group, extended acute inflammatory reactions have to be suggested because of elevated CRP- values and decreased leukocyte counts. Additionally, we found worse MURRAY- scores and elevated AaDO2 gradients in the “high AOC” group. If progressive subsequent myocardial ischemia in the “low AOC” group is the main inducer of lower buffer capacity is still under investigation. Kim and co-workers investigated the association between a systemic inflammation and 10-year risk for coronary heart disease (CHD) in healthy adults in the U. S. They found a low-grade systemic inflammation and hyperhomocysteinemia as an indicator for a higher risk for CHD. In reaction to surgical trauma and ECC the constant low AOC in the correlating group of our study could be seen as a preconditioning effect. These effects result in a stable postoperative time course. Otherwise, in the group with high preoperative AOC levels we suggest no preoperative inflammatory reaction and a primary answer on the surgical impact. Therefore, a release of cytokines and ROS- production with successive affection of the lungs can easily be explained. A study on Interleukin- 18 levels in unstable angina recovers different inflammatory pathways, we did not adress during our analysis. Different groups have pronounced the relative value of Leukocyte counts and CRP in the diagnostic schedule for the risk of CHD. Chronic obstructive pulmonary disease also appears in this context as a rather moderate affector, although known to be linked to cardio-vascular diseases. Moreover, progression in heart failure itself contributes to an increased oxidative stress by a higher activity of myocardial NADPH oxidase. In our study we found no differences in cardiac output, severity of arteriosclerosis (see number of bypass- transplants), age, body mass index or preoperative left ventricle enddiastolic pressure. Because of the “superficial homogeneity” of our patients we recommend the preoperative evaluation of AOC in randomized studies with larger groups of patients to validate the predictive value as a helpful tool for detection of risk groups in patients undergoing cardiovascular surgery and with the intention to pharmacological perioperative treatment. Herein consideration has to be focused on the interactions of CHD, gender, age and Lipoprotein serum composition with the antioxidative status.