Vascular endothelial growth factor gene therapy induces early re-establishment of canine bronchial circulation.

OBJECTIVE: To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF(165)) to promote the early re-establishment of systemic arterial perfusion in canine bronchi deprived of bronchial circulation. METHODS: To disrupt bronchial circulation, dogs were submitted to transversal bronchotomy dividing the left mainstem bronchus into a proximal and a distal portion. phVEGF(165) (VEGF group, n=8) or physiologic saline solution (control group, n=8) were then delivered to the left distal bronchus. After that, the airway was reconstituted with interrupted suture. On day 3, nine dogs (four VEGF and five controls) were euthanized and their left distal bronchi were harvested to evaluate VEGF(165) gene expression by reverse transcription-polymerase chain reaction. In the other dogs (four VEGF and three controls), a microvascular dye was injected through the canine aorta to verify the re-establishment of arterial blood supply to the distal bronchus. Additionally, VEGF immunohistochemistry was performed in distal airway specimens. RESULTS: Microvascular dye was observed in 100% of specimens transfected with phVEGF(165) compared to none in controls. VEGF gene expression (p<0.01) and VEGF protein expression (p<0.05) were higher in VEGF(165)-treated bronchi. CONCLUSIONS: Local transfection with phVEGF(165) promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF(165) may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.

Transbronchoscopic pulmonary emphysema treatment: 1-month to 24-month endoscopic follow-up.

OBJECTIVE: Describe the results of a 1- to 24-month follow-up of individuals undergoing transbronchoscopic placement of one-way valves. DESIGN: Longitudinal, noncomparative study. SETTING: University hospital. PATIENTS: Nineteen heterogeneous emphysema patients. MEASUREMENTS AND RESULTS: Pulmonary function testing, imaging examination, and videobronchoscopy were performed at 1, 3, 6, 12, and 24 months after the insertion of one-way valves. Mean age was 67.63 +/- 8.71 years, mean body mass index (BMI) was 24.02 +/- 2.65, and mean exposure to smoking was 65.32 +/- 27.46 pack-years (+/- SD). Baseline BODE index (BMI, degree of airflow obstruction and dyspnea, exercise capacity as measured by the 6-min walk test [6MWT]) was 7 to 10 in 10 patients (estimated 4-year mortality, 80%) and 5 to 6 in 9 patients (estimated 4-year mortality, 40%). Sixty-four valves were inserted. There was no procedure-related mortality. Nonsustained atelectasis was observed within 48 h in 2 of 12 patients with right upper lobe occlusion. Fifty-six bronchoscopic examinations were performed in 24 months. Granulomas not requiring treatment were the main complication. Mucus clogging the valve, mainly at 1 month, was easily cleaned. Eighteen patients completed the 1- and 3-month follow-ups, 14 patients completed the 6-month follow-up, 11 patients completed the 12-month follow-up, and 5 patients completed the 24-month follow-up. Improvement was observed in the 6MWT after 1 month (p = 0.028) and in the BODE index at 3 months (p = 0.002). FEV1 or FVC improvement > or = 12% or > or = 150 mL was observed, respectively, in 4 of 18 patients and 8 of 18 patients at 1 month, 4 of 18 patients and 7 of 18 patients at 3 months, and in 3 of 14 patients and 5 of 14 patients at 6 months. After 24 months, one of five patients and three of five patients, respectively, retained an FEV1 and FVC change > or = 12% or > or = 150 mL. Significant improvement (decrease > or = 4%) in the St. George Respiratory Questionnaire was observed at 3 months and 6 months in three of four domains. CONCLUSION: Endobronchial valves are safe, but the criteria to measure improvement and to select patients should be refined. Atelectasis should be reconsidered as primary treatment goal.

Clinical efficacy of dexmedetomidine alone is less than propofol for conscious sedation during ERCP.

BACKGROUND: Propofol is an accepted method of sedation for an ERCP and generally achieves deep sedation rather than conscious sedation, and dexmedetomidine has sedative properties of equivalent efficacy. OBJECTIVE: To examine the hypothesis that dexmedetomidine is as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP. DESIGN AND SETTING: Randomized, blind, double-dummy clinical trial. PATIENTS: Twenty-six adults, American Society of Anesthesiologists status I to III, underwent an ERCP. INTERVENTIONS: Patients were randomized to receive either propofol (n = 14) (target plasma concentration range 2-4 microg/mL) combined with fentanyl 1 microg/kg, or dexmedetomidine (n = 12) 1 microg/kg for 10 minutes, followed by 0.2 to 0.5 microg/kg/min. Additional sedatives were used if adequate sedation was not achieved at the maximum dose allowed. MAIN OUTCOMES MEASUREMENTS: The sedation level was assessed by the Richmond alertness-sedation scale and the demand for additional sedatives. Furthermore, heart rate, blood pressure, oxygen saturation, and respiratory rate were continuously assessed. RESULTS: The relative risk (RR) was 2.71 (95% CI, 1.31-5.61) and the number of patients that needed to be treated (NNT) was 1.85 (95% CI, 1.19-4.21) to observe one additional patient with drowsiness 15 minutes after sedation in the dexmedetomidine group. Also, the RR was 9.42 (95% CI, 1.41-62.80), and the NNT was 1.42 (95% CI, 1.0-2.29) to require additional analgesic. However, there was also a greater reduction in blood pressure, a lower heart rate, and greater sedation after the procedure. CONCLUSIONS: Dexmedetomidine alone was not as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP. Furthermore, dexmedetomidine was associated with greater hemodynamic instability and a prolonged recovery.