| dc.contributor.advisor | Hinz, José Prof. Dr. | |
| dc.contributor.author | Bireta, Christian | |
| dc.date.accessioned | 2015-04-13T10:12:46Z | |
| dc.date.available | 2015-04-21T22:50:11Z | |
| dc.date.issued | 2015-04-13 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0022-5FAE-1 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5023 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Einfluss des eNOS T-786C-Polymorphismus auf die 5-Jahres-Mortalität und -Morbidität von Patienten nach herzchirurgischen Eingriffen | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | The eNOS T-786C gene polymorphism and its influence on 5-year mortality and morbidity after on-pump cardiac surgery | de |
| dc.contributor.referee | Hinz, José Prof. Dr. | |
| dc.date.examination | 2015-04-14 | |
| dc.description.abstracteng | Nitric oxide (NO) is an endothelium-derived relaxing factor (EDRF) which represents one of the most relevant molecules involved in biological systems. NO is produced by three nitric oxide synthase (NOS) isoforms: neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) from L-arginine. eNOS is the key enzyme responsible for basal vascular production of NO. The human eNOS gene is located on the chromosome 7 (7q35-36) which consists of 26 exons with an entire length of 21 kb and is constitutively expressed in vascular endothelial cells. Apart from influencing the relaxation of vascular smooth muscle cells, endothelium-derived NO inhibits platelets and leukocytes adhesion to the vascular wall, inhibits vascular smooth cell migration and proliferation, and limits the oxidation of atherogenic low-density lipoproteins. Due to these vasoprotective and anti-atherosclerotic properties it plays a crucial role in the cardiovascular system.
Changes in NO bioavailability have been associated with various diseases of the vascular system such as atherosclerosis, coronary artery disease, coronary spasm and a higher incidence of myocardial infarction. Furthermore, it has been shown that the production of NO is significantly altered during and after cardiopulmonary bypass (CPB). Therefore, changes in eNOS activity and NO bioavailability after cardiac surgery with CPB may lead to vasomotor abnormalities with impaired regulation of myocardial perfusion, altered peripheral vascular resistance, and vascular permeability. Several genetic polymorphism of the eNOS gene has been shown to influence the functional activity of the enzyme and accordingly the NO bioavailability. The eNOS T-786C polymorphism is associated with a decreased promoter activity of the eNOS gene, which leads to a reduced constitutive NO production. Its role in the postoperative course after cardiac surgery has been investigated, however with debating results. In the current study we examine the impact of the eNOS T-786C polymorphism on long term mortality and morbidity after on-pump cardiac surgery.
After approval by the local ethics committee (30/7/05), data of 500 adult patients who underwent cardiac surgery with CPB were analyzed. The determination of the polymorphism was performed by real time PCR and patients were divided into three subgroups according to their genotype: TT, TC and CC. To obtain data regarding the long term mortality and morbidity, data collection was carried out after five years through a special designed questionnaire addressed to the corresponding general practitioner, direct patient contact and obtaining information by the local registration office.
The long-term follow up was complete in all cases and the follow-up time of approximately 5 years. The overall mortality was 25% (n=125) and there was no statistically significant difference with regard to genotype distribution (p=0.09). This mortality is comparable with other international studies and reflects the general mortality of cardiac surgery patients. However, homozygous CC-carriers showed an impaired survival but without statistical significance. Protocol dropouts did not allow for a safe five year morbidity statement. Thus, no genotype was detected as a potential risk factor for increased long-term mortality. Therefore the eNOS T-786C polymorphism can not be used as an independent risk factor for estimating individual survival rates and is not suitable as a screening parameter in long-term mortality of cardiac surgery patients. | de |
| dc.contributor.coReferee | Bickeböller, Heike Prof. Dr. | |
| dc.contributor.thirdReferee | Brockmöller, Jürgen Prof. Dr. | |
| dc.subject.ger | Herzchirurgie | de |
| dc.subject.ger | Genetik | de |
| dc.subject.ger | Stickstoffmonoxid (NO) | de |
| dc.subject.ger | T-786C-Polymorphismus | de |
| dc.subject.eng | cardiac surgery | de |
| dc.subject.eng | genetics | de |
| dc.subject.eng | nitric oxide | de |
| dc.subject.eng | T-786C polymorphism | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5FAE-1-9 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Medizin (PPN619874732) | de |
| dc.subject.gokfull | Herzchirurgie (PPN619875992) | de |
| dc.description.embargoed | 2015-04-21 | |
| dc.identifier.ppn | 821981129 | |