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Alterations in plasma soluble vascular endothelial growth factor receptor-1 (sFlt-1) concentrations during coronary artery bypass graft surgery: relationships with post-operative complications.

Denizot Y, Leguyader A, Cornu E, Laskar M, Orsel I, Vincent C, Nathan N - J Cardiothorac Surg (2008)

Bottom Line: Patients with and without complications had similar pre-operative plasma sFlt-1 levels.Lowered plasma sFlt-1 levels were observed at the end of ECC in patients with haematological (p = 0.001, ANOVA) or cardiovascular (p = 0.006) impairments, but not with respiratory ones (p = 0.053), as compared to patients with uneventful surgery.These results identify an association between specific post-CABG complication and the lower release of sFlt-1 during ECC. sFlt-1-induced VEGF neutralisation might, thus, be beneficial to reduce the development of post-operative adverse effects after CABG.

View Article: PubMed Central - HTML - PubMed

Affiliation: UMR CNRS 6101, Centre National de la Recherche Scientifique, Université de Limoges, France. yves.denizot@unilim.fr

ABSTRACT

Background: Plasma concentrations of sFlt-1, the soluble form of the vascular endothelial growth factor receptor (VEGF), markedly increase during coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). We investigated if plasma sFlt-1 values might be related to the occurrence of surgical complications after CABG.

Methods: Plasma samples were collected from the radial artery catheter before vascular cannulation and after opening the chest, at the end of ECC just before clamp release, after cross release, after weaning from ECC, at the 6th and 24th post-operative hour. Thirty one patients were investigated. The presence of cardiovascular, haematological and respiratory dysfunctions was prospectively assessed. Plasma sFlt-1 levels were measured with commercially ELISA kits.

Results: Among the 31 investigated patients, 15 had uneventful surgery. Patients with and without complications had similar pre-operative plasma sFlt-1 levels. Lowered plasma sFlt-1 levels were observed at the end of ECC in patients with haematological (p = 0.001, ANOVA) or cardiovascular (p = 0.006) impairments, but not with respiratory ones (p = 0.053), as compared to patients with uneventful surgery.

Conclusion: These results identify an association between specific post-CABG complication and the lower release of sFlt-1 during ECC. sFlt-1-induced VEGF neutralisation might, thus, be beneficial to reduce the development of post-operative adverse effects after CABG.

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Related in: MedlinePlus

Comparison of plasma sFlt-1 levels for complicated and uncomplicated patients during the course of CABG. Plasma sFlt-1 values are expressed in pg per mg protein. T0: before vascular cannulation and after opening the chest; T1: during extracorporeal circulation (ECC); T2: at the end of ECC before cross clamp release; T3: after cross clamp release; T4: the 6th post-operative hour; T5: the 24th post-operative hour. A: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 7 patients with hematological impairments (open squares). B: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 9 patients with cardiovascular impairments (open squares). C: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 13 patients with respiratory impairments (open squares). D: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 3 patients who died postoperatively (open squares). Results were expressed as means ± SD Statistical differences were made using ANOVA test.
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Figure 2: Comparison of plasma sFlt-1 levels for complicated and uncomplicated patients during the course of CABG. Plasma sFlt-1 values are expressed in pg per mg protein. T0: before vascular cannulation and after opening the chest; T1: during extracorporeal circulation (ECC); T2: at the end of ECC before cross clamp release; T3: after cross clamp release; T4: the 6th post-operative hour; T5: the 24th post-operative hour. A: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 7 patients with hematological impairments (open squares). B: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 9 patients with cardiovascular impairments (open squares). C: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 13 patients with respiratory impairments (open squares). D: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 3 patients who died postoperatively (open squares). Results were expressed as means ± SD Statistical differences were made using ANOVA test.

Mentions: When sFlt-1 was evaluated during the course of CABG surgery significant differences were found between complicated and uneventful patients. Thus, lower circulating sFlt-1 levels were observed in patients with hematological (p = 0.001, ANOVA test) and cardiovascular (p = 0.006) impairments (Figure 2A and 2B, respectively). In contrast sFlt-1 values were not significantly (p = 0.053) different in patients with respiratory impairments as compared with uneventful patients (Fig 2C). Finally lower sFlt-1 levels (p = 0.013) were also evidenced for the 3 patients who died postoperatively (Figure 2D). This study confirms in a set of complicated patients the release of sFlt-1 during CABG with ECC; sFlt-1 values of uneventful patients being previously reported separately [14]. In this study all patients received aprotinin. The use of aprotinin in cardiac surgery is currently the subject of much debate since aprotinin might have modified the inflammatory response of our patients [18]. However all patients (both uneventful and complicated) received aprotinin. Thus, it is not the use of aprotinin by itself that reduced sFlt-1 release in complicated patients. In this study we investigated CABG surgery with ECC. In the last few years, off-pump coronary artery bypass grafting has gained widespread attention as an alternative technique to conventional on-pump coronary artery bypass grafting. However the available literature does not permit definitive conclusions to be made on the advantages of off-pump surgery with respect to the systemic inflammatory response [19]. Moreover mortality, stroke, myocardial infarction and renal failure were not improved [20]. Clearly investigation of sFlt-1 and VEGF release during off-pump cardiac surgery would be of interest to ensure the involvement of angiogenic/anti-angionic pathways during this type of cardiac surgery.


Alterations in plasma soluble vascular endothelial growth factor receptor-1 (sFlt-1) concentrations during coronary artery bypass graft surgery: relationships with post-operative complications.

Denizot Y, Leguyader A, Cornu E, Laskar M, Orsel I, Vincent C, Nathan N - J Cardiothorac Surg (2008)

Comparison of plasma sFlt-1 levels for complicated and uncomplicated patients during the course of CABG. Plasma sFlt-1 values are expressed in pg per mg protein. T0: before vascular cannulation and after opening the chest; T1: during extracorporeal circulation (ECC); T2: at the end of ECC before cross clamp release; T3: after cross clamp release; T4: the 6th post-operative hour; T5: the 24th post-operative hour. A: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 7 patients with hematological impairments (open squares). B: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 9 patients with cardiovascular impairments (open squares). C: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 13 patients with respiratory impairments (open squares). D: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 3 patients who died postoperatively (open squares). Results were expressed as means ± SD Statistical differences were made using ANOVA test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2365942&req=5

Figure 2: Comparison of plasma sFlt-1 levels for complicated and uncomplicated patients during the course of CABG. Plasma sFlt-1 values are expressed in pg per mg protein. T0: before vascular cannulation and after opening the chest; T1: during extracorporeal circulation (ECC); T2: at the end of ECC before cross clamp release; T3: after cross clamp release; T4: the 6th post-operative hour; T5: the 24th post-operative hour. A: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 7 patients with hematological impairments (open squares). B: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 9 patients with cardiovascular impairments (open squares). C: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 13 patients with respiratory impairments (open squares). D: sFlt-1 levels in 15 uncomplicated patients (solid squares) and 3 patients who died postoperatively (open squares). Results were expressed as means ± SD Statistical differences were made using ANOVA test.
Mentions: When sFlt-1 was evaluated during the course of CABG surgery significant differences were found between complicated and uneventful patients. Thus, lower circulating sFlt-1 levels were observed in patients with hematological (p = 0.001, ANOVA test) and cardiovascular (p = 0.006) impairments (Figure 2A and 2B, respectively). In contrast sFlt-1 values were not significantly (p = 0.053) different in patients with respiratory impairments as compared with uneventful patients (Fig 2C). Finally lower sFlt-1 levels (p = 0.013) were also evidenced for the 3 patients who died postoperatively (Figure 2D). This study confirms in a set of complicated patients the release of sFlt-1 during CABG with ECC; sFlt-1 values of uneventful patients being previously reported separately [14]. In this study all patients received aprotinin. The use of aprotinin in cardiac surgery is currently the subject of much debate since aprotinin might have modified the inflammatory response of our patients [18]. However all patients (both uneventful and complicated) received aprotinin. Thus, it is not the use of aprotinin by itself that reduced sFlt-1 release in complicated patients. In this study we investigated CABG surgery with ECC. In the last few years, off-pump coronary artery bypass grafting has gained widespread attention as an alternative technique to conventional on-pump coronary artery bypass grafting. However the available literature does not permit definitive conclusions to be made on the advantages of off-pump surgery with respect to the systemic inflammatory response [19]. Moreover mortality, stroke, myocardial infarction and renal failure were not improved [20]. Clearly investigation of sFlt-1 and VEGF release during off-pump cardiac surgery would be of interest to ensure the involvement of angiogenic/anti-angionic pathways during this type of cardiac surgery.

Bottom Line: Patients with and without complications had similar pre-operative plasma sFlt-1 levels.Lowered plasma sFlt-1 levels were observed at the end of ECC in patients with haematological (p = 0.001, ANOVA) or cardiovascular (p = 0.006) impairments, but not with respiratory ones (p = 0.053), as compared to patients with uneventful surgery.These results identify an association between specific post-CABG complication and the lower release of sFlt-1 during ECC. sFlt-1-induced VEGF neutralisation might, thus, be beneficial to reduce the development of post-operative adverse effects after CABG.

View Article: PubMed Central - HTML - PubMed

Affiliation: UMR CNRS 6101, Centre National de la Recherche Scientifique, Université de Limoges, France. yves.denizot@unilim.fr

ABSTRACT

Background: Plasma concentrations of sFlt-1, the soluble form of the vascular endothelial growth factor receptor (VEGF), markedly increase during coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). We investigated if plasma sFlt-1 values might be related to the occurrence of surgical complications after CABG.

Methods: Plasma samples were collected from the radial artery catheter before vascular cannulation and after opening the chest, at the end of ECC just before clamp release, after cross release, after weaning from ECC, at the 6th and 24th post-operative hour. Thirty one patients were investigated. The presence of cardiovascular, haematological and respiratory dysfunctions was prospectively assessed. Plasma sFlt-1 levels were measured with commercially ELISA kits.

Results: Among the 31 investigated patients, 15 had uneventful surgery. Patients with and without complications had similar pre-operative plasma sFlt-1 levels. Lowered plasma sFlt-1 levels were observed at the end of ECC in patients with haematological (p = 0.001, ANOVA) or cardiovascular (p = 0.006) impairments, but not with respiratory ones (p = 0.053), as compared to patients with uneventful surgery.

Conclusion: These results identify an association between specific post-CABG complication and the lower release of sFlt-1 during ECC. sFlt-1-induced VEGF neutralisation might, thus, be beneficial to reduce the development of post-operative adverse effects after CABG.

Show MeSH
Related in: MedlinePlus