Effect of implantation site on outcome of tissue-engineered vascular grafts.

OBJECTIVE: Vascular prostheses for small caliber bypass grafts in cardiac and vascular diseases or for access surgery are still missing. Poly (Ɛ-caprolactone) (PCL) has been previously investigated by our group and showed good biocompatibility and mechanical properties in vitro and rapid endothelialisation, cellular infiltration and vascularisation in vivo yielding optimal patency in the abdominal aortic position. The aim of the present study is to evaluate our PCL graft in the carotid position and to compare its outcome to the grafts implanted in the abdominal aortic position. METHODS: PCL grafts (1 mm ID/10 mm long) were implanted into the left common carotid artery in 20 Sprague-Dawley rats and compared to our previously published series of abdominal aortic implants. The animals were followed up to 3, 6, 12 and 24 weeks. At each time point, in vivo compliance, angiography and histological examination with morphology were performed. RESULTS: PCL grafts showed good mechanical properties and ease of handling. The average graft compliance was 14.5 ±â€¯1.7%/ mmHg compared to 7.8 ±â€¯0.9% for the abdominal position and 45.1 ±â€¯3.2%/ mmHg for the native carotid artery. The overall patency for the carotid position was 65% as compared to 100% in the abdominal position. Complete endothelialisation was achieved at 3 weeks and cell invasion was more rapid than in the aortic position. In contrast, intimal hyperplasia (IH) and vascular density were less pronounced than in the aortic position. CONCLUSION: Our PCL grafts in the carotid position were well endothelialised with early cellular infiltration, higher compliance, lower IH and calcification compared to the similar grafts implanted in the aortic position. However, there was a higher occlusion rate compared to our abdominal aorta series. Anatomical position, compliance mismatch, flow conditions may answer the difference in patency seen.

A novel high vacuum chest drainage system - a pilot study.

AIM: To assess the safety and feasibility of use of a novel high vacuum chest drainage system (HVCDS) and its influence on the cardiovascular system compared to a conventional system (CCDS). MATERIAL AND METHODS: Five anesthetized pigs underwent a median sternotomy. Three drains were placed in retrocardiac, retrosternal and left pleural positions. The animals received a HVCDS (22 Fr with 180 2-mm holes, n = 2) or a CCDS (n = 2). In the fifth animal off pump coronary artery bypass graft (OPCABG) stabilizers were tested. After chest closure animals had three 30 min runs of artificial bleeding (5 ml/min) under different negative aspiration pressures (-2, -20, -40 kPa) for both groups, followed by standardized surgical bleeding (-40 kPa - HVCDS, - 2 kPa - CCDS). Hemodynamic parameters and each drain's output were registered every 5 minutes and the residual blood was assessed. All catheters, the heart and left lung underwent macroscopic and histopathological examination. RESULTS: The application of the different pressures showed neither hemodynamic changes nor differences in blood drainage with both systems in two bleeding models. The HVCDS enabled drainage comparable to the CCDS but showed relevant clotting. Application of -20 kPa and -40 kPa caused macroscopic epicardial and pulmonary lesions in all tested devices including OPCABG stabilizers consisting of sub-epicardial or sub-pleural hemorrhage without myocyte or alveolar damage. CONCLUSIONS: The novel and conventional chest drainage systems used at pressures up to 40 kPa induced no hemodynamic instability. Both systems showed adequate equal drainage, despite major HVCDS clotting. High negative pressure drainage with both systems showed focal sub-epicardial and subpleural hemorrhage. Thus, long-term assessment of high pressure drainage and potential interaction with fragile structures (coronary bypass graft) should be carried out.

Biodegradable PLGA microparticles for sustained release of a new GnRH antagonist: part II. In vivo performance.

Poly (DL-lactide-co-glycolide) microparticles (MP) containing a highly potent peptidic gonadotropin releasing hormone antagonist (degarelix) of interest in the prostate cancer indication were screened for biological performance. Efficacy was tested in a castrated male rat model at 3 doses (0.4, 1.0 and 1.5 mg/kg) and assessed as inhibition of luteinizing hormone (LH) secretion. When increasing the dose, onset of inhibition was faster, inhibition was more intense, and duration of action was prolonged. The MP type was also highly influent. If spray-dried and microextrusion particles exhibited comparable potencies, double emulsion microspheres were significantly less potent, both for onset and duration of inhibition. Interestingly, for the latter type it was found that the degarelix fraction released upon reconstitution in the solution for injection was significantly lower (max 0.3%), in comparison to spray-dried MP (max 2%) or microextrusion (max 4%). With the three types of particles, increasing peptide content was detrimental for duration of action, but only little difference was noticed between particles based on different polymers. At 1.5 mg/kg, LH inhibition was achieved over 36 days with spray-dried MP based on 75/25 lactate/glycolate copolymer. This was superior by 1 week to the performance of unformulated degarelix given at the same dose.