Publikationsserver der RWTH Aachen University
Expression des 'Vascular endothelial growth factor' bei Kindern mit angeborenem Herzfehler : Einfluss der präoperativen Hypoxämie und der Herzoperation
Abstract
dc:descriptionChildren with cyanotic congenital heart disease (C-CHD) often develop collateral blood vessels that could be interpreted as a form of abnormal angiogenesis (Starnes et al., 2000). Since vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, we examined in this study whether children with cyanotic congenital heart disease have elevated plasma levels of VEGF in comparison to children with acyanotic congenital heart disease (A-CHD), and if there is a correlation between plasma VEGF levels and the expression of VEGF-mRNA in the myocardium. To test the hypothesis if VEGF has a protective influence on the cardiovascular system and on the postoperative course, we measured the plasma levels of VEGF during and after cardiac surgery. 27 patients, who underwent heart surgery with extracorporeal circulation (ECC), were divided into 2 groups: the C-CHD group (n = 15) and the A-CHD group (n = 12). Median age of the whole study population was 4,5 months (Range 0,3 - 19,5 months). Median age was 5,0 (0,3 - 19,5) months in the cyanotic group and 4,3 (2,5 - 13,5) months in the acyanotic group. Blood samples were collected pre-, intra- and postoperatively and a biopsy of myocardium (right atrium) was taken during the operation. VEGF concentrations were measured in the plasma by enzyme-linked immunosorbent assay (ELISA). The VEGF-mRNA expression in the myocardium was detected by Real-Time-Polymerase Chain Reaction (Real-Time-PCR). Results were analyzed with respect to preoperative clinical data, ECC-parameters, postoperative clinical data and postoperative laboratory findings, respectively. Mean systemic oxygen saturation (SaO2) and plasma VEGF levels were measured preoperatively to verify the influence of preoperative hypoxaemia on the expression of VEGF. Before the operation, plasma VEGF levels were higher in the C-CHD group compared to the A-CHD group, but the difference did not reach statistical significance (71,24 ± 17,95 pg/ml vs. 60,51 ± 15,16 pg/ml). No correlation was found between preoperative VEGF levels and arterial oxygen saturation, even though mean systemic oxygen saturation was significantly lower in the cyanotic group than in the acyanotic group (85,13 ± 2,39 % vs. 97,33 ± 0,60 %, p < 0,001). Postoperative plasma VEGF levels (taken 24h after surgery) were markedly reduced (factor 2) compared to the preoperative values. After starting the ECC, VEGF levels decreased significantly in both groups (C-CHD group and A-CHD group: p < 0,005). While in the A-CHD group VEGF levels continuously dropped until the end of the operation, the C-CHD group VEGF levels increased immediately after ECC was stopped. Furthermore, the plasma VEGF levels increased postoperatively in both groups. The mean value of VEGF-mRNA copies was higher in the A-CHD group than in the C-CHD group (1,77 ± 0,06 vs. 1,53 ± 0,09, p = 0,06). This suggests that the myocardium of children with C-CHD may be a location of lower transcription of VEGF-mRNA in comparison to other organs. Since the plasma levels of VEGF were higher in patients with C-CHD, a lower myocardial expression of VEGF may lead to a compensatory overexpression of VEGF in other cells and organs induced by hypoxaemia. We could not show any correlation between plasma VEGF and myocardial VEGF-mRNA for the whole group (C-CHD group and A-CHD group). However, in the A-CHD subgroup, plasma VEGF levels correlated with the expression of myocardial VEGF-mRNA (p = 0,05). In our study the expression of VEGF (in plasma and myocardium) was not correlated with patient’s age. However patient’s age had an influence on ECC-parameters, cardiovascular complications and the postoperative period. Indeed, younger children showed a greater risk for complications. The results of the present study demonstrate that the plasma VEGF levels (systemic production) were higher in the C-CHD group than in the A-CHD group. In contrast, the expression of myocardial VEGF-mRNA tended to be higher in the A-CHD group than in the C-CHD group. While the expression of myocardial VEGF-mRNA had a protective influence, the plasma levels of VEGF correlated with poor outcome.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2009
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Fenske, Eva
- Contributors dc:contributor
-
- Seghaye, Marie-Christine
Subjects
dc:subject × 12Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger