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

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.

Release of soluble vascular endothelial growth factor receptor-1 (sFlt-1) during coronary artery bypass surgery.

BACKGROUND: This study was conducted to follow plasma concentrations of sFlt-1 and sKDR, two soluble forms of the vascular endothelial growth factor (VEGF) receptor in patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). METHODS: Plasma samples were obtained before, during and after surgery in 15 patients scheduled to undergo CABG. Levels of sFlt-1 and KDR levels were investigated using specific ELISA. RESULTS: A 75-fold increase of sFlt-1 was found during cardiac surgery, sFlt-1 levels returning to pre-operative values at the 6th post-operative hour. In contrast sKDR levels did not change during surgery. The ECC-derived sFlt-1 was functional as judge by its inhibitory effect on the VEGF mitogenic response in human umbilical vein endothelial cells (HUVECs). Kinetic experiments revealed sFlt-1 release immediately after the beginning of ECC suggesting a proteolysis of its membrane form (mFlt-1) rather than an elevated transcription/translation process. Flow cytometry analysis highlighted no effect of ECC on the shedding of mFlt-1 on platelets and leukocytes suggesting vascular endothelial cell as a putative cell source for the ECC-derived sFlt-1. CONCLUSION: sFlt-1 is released during CABG with ECC. It might be suggested that sFlt-1 production, by neutralizing VEGF and/or by inactivating membrane-bound Flt-1 and KDR receptors, might play a role in the occurrence of post-CABG complication.

Platelet activation after aortic prosthetic valve surgery.

OBJECTIVES: Platelet activation, which may lead to thrombus formation, is poorly understood after valve surgery when analysed by flow cytometry. It is still unclear whether platelet activation is due to the implanted prosthesis itself or to its aortic or mitral position. The present prospective study was aimed at assessing platelet P-selectin expression, platelet-leukocyte conjugate formation and platelet microparticles and comparing biological, bileaflet and tilting disc valvular prostheses in aortic position. METHODS: Thirty-three patients were included (15 bioprostheses, 11 bileaflet and 7 tilting disc mechanical valves). Blood samples were analyzed by flow cytometry immediately before surgery, on postoperative day 8 (D8) and 2 months after surgery (M2). RESULTS: At D8, patients with bileaflet valves demonstrated a significant increase in platelet-leukocyte conjugates and in platelet microparticles whereas only platelet-monocyte conjugates were significantly increased in patients with bioprostheses. At M2, platelet activation had returned to the basic level observed prior to surgery in the bileaflet valve group whereas, it was still increased in the bioprosthesis group. Neither at D8 nor at M2 did patients with tilting disc mechanical valves demonstrate any platelet activation. CONCLUSIONS: Platelet activation after aortic valve replacement was observed with the use of bioprostheses and bileaflet mechanical valves, but not with tilting disc mechanical valves.