Vascular endothelial growth factor increases pulmonary vascular permeability in cystic fibrosis patients undergoing lung transplantation.

Vascular endothelial growth factor (VEGF) is the prime regulator of angiogenesis and vascular permeability and its serum levels increase in cystic fibrosis (CF). The mechanisms of VEGF overproduction and its impact on CF lung pathology and pulmonary vascular permeability during lung transplantation are not fully understood. The expression of VEGF, its receptors, hypoxia inducible factor (HIF)-1alpha, beta, angiopoietins, and endothelial cell marker CD31 were studied in lung biopsies of CF and COPD patients and controls, using real time reverse transcription (RT)-PCR and Western blotting. DNA binding activity of HIF-1 to VEGF-A promoter was assessed by electrophoretic mobility shift assay (EMSA) and wet-to-dry lung weight ratios as well as microvascular density (MVD) were determined. Serum VEGF-A concentrations in enzyme-linked immunosorbent assay (ELISA) and wet-to-dry weight ratios of donor lungs were monitored during transplantation in CF and COPD patients. Primary graft dysfunction (PGD) was diagnosed and graded according to the guidelines of the International Society for Heart and Lung Transplantation. VEGF-A165 and Flt-1 mRNA expression (P<0.05), VEGF-A (P<0.05), and HIF-1alpha (P<0.05) protein levels, DNA binding activity of HIF-1 to VEGF promoter (P<0.001) and extravascular lung water content (P<0.05) were increased in CF lungs versus controls, whereas MVD was unchanged. Before and during lung transplantation, VEGF-A serum concentrations were higher in CF versus COPD patients (P<0.05) and 60 min following reperfusion donor lungs transplanted to CF patients had higher tissue water contents than in COPD patients (P<0.05). PGD grade 3 occurred more frequently in CF (22.7%) versus COPD patients (4%). PGD grade 3 patients had significantly higher VEGF serum concentrations versus PGD grade 0-2 patients (P<0.001). These data indicate that upregulated VEGF-A levels are most likely induced by enhanced HIF-1 binding to VEGF-A promoter, possibly contributing to elevated serum VEGF-A levels in CF. Furthermore, CF patients undergoing lung transplantation are possibly more susceptible to PGD because of increased VEGF-A expression that mediates increased lung graft vascular permeability.

被引量：- 发表：1970

Post-traumatic hernia of the lung.

被引量：1 发表：2001

Expanded polytetrafluoroethylene membranes to wrap surfaces of circulatory support devices in patients undergoing bridge to heart transplantation.

OBJECTIVE:Because of a lack of donor hearts, an increasing number of patients with heart failure must now undergo bridge to cardiac transplantation with a mechanical circulatory support device. Moreover, support periods have become longer. As a result, pericardial adhesions may develop while the support device is implanted, increasing the risk of injury at resternotomy and bleeding after transplantation. Use of expanded polytetrafluoroethylene (ePTFE) pericardial substitutes (membranes) may prevent such adhesions. PATIENTS AND METHODS:From January 1997 to December 1999, ePTFE membranes were used in 23 patients to wrap portions of an implanted left ventricular assist device (LVAD) or total artificial heart (TAH). Any complications during mechanical support or at cardiac transplantation were recorded. Six ePTFE membranes removed at transplantation were studied histologically. RESULTS AND CONCLUSIONS:At resternotomy for transplantation, the plane of dissection between tissues, ePTFE membranes, and surfaces of the mechanical support device were easily discerned. No adhesions were observed between tissues and membranes. There were no injuries during resternotomy and no patient had to undergo reoperation because of bleeding. One patient given a TAH had an infection during circulatory support that was controlled by antibiotic therapy. In another patient, clots developed between the device and an ePTFE membrane; these were removed successfully. Histologic studies of removed ePTFE membranes showed no infiltration of the membranes interstices by collagen or cellular components. Use of ePTFE membranes in patients undergoing bridge to transplantation with either an LVAD or a TAH limited adhesions between tissues and device surfaces without increasing the risk of infection.

被引量：- 发表：2001

Outcome of non-elective coronary artery bypass grafting without cardio-pulmonary bypass.

OBJECTIVES:There is limited experience in the use of beating heart coronary artery bypass grafting (CABG) in emergency and urgent cases. The aim of this study was to retrospectively assess the safety and efficacy of this technique when used in a non-elective setting. METHODS:We retrospectively reviewed all urgent and emergency cases of coronary artery bypass grafting performed without cardiopulmonary bypass (CPB) from July 1999 to February 2000. There were 35 patients in total. The mean age was 64.8+/-11.9. Twenty-six (74.3%) patients had Canadian Cardiovascular Society grade 4 angina. Twenty-six patients (74.3%) had triple vessel disease. Eleven patients (31.4%) were on preoperative IV nitrates and nine patients (25.7%) had a preoperative IABP (intra aortic balloon pump). Three patients (8.6%) had suffered a preoperative cardiac arrest during coronary angiography. Other associated significant risk factors were smoking (60%), hypertension (40%), hypercholesterolemia (57.1%) and previous Q wave myocardial infarction (31.4%). RESULTS:Twenty-two patients (62.9%) were classified as being urgent and 13 patients (37.1%) were classified as emergencies. The mean number of anastomoses performed were 2.8+/-0.8 (range 1-4) with 68.6% of patients under going triple or quadruple vessel grafting. All patients (100%) received at least one arterial graft. There was no conversion to cardiopulmonary bypass. The main postoperative complications were--supraventricular arrhythmias eight (22.9%), low cardiac output seven (20%) and postoperative HF/dialysis two (5.7%). The median postoperative intensive care unit (ICU) stay was 27.5 h. The mean postoperative hospital stay was 8.3+/-3.1 days. One patient died (2.9%) at the eighth day after surgery due to postoperative myocardial infarction, multi-organ failure secondary to the septicaemia and ventricular arrest. CONCLUSION:Non-elective CABG without CPB is feasible and safe with modern cardiac stabilization devices.

被引量：3 发表：2001

Neuroprotective effects of pre-treatment with systemic steroids in a neonatal piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest.

被引量：- 发表：2000