A polyhydroxybutyrate biodegradable stent: preliminary experience in the rabbit.

PURPOSE: The lifelong persistence of foreign bodies within the arteries may contribute to restenosis. Thus, biodegradable devices might decrease recurrence rates. METHODS: Eleven polyhydroxybutyrate biodegradable stents and 13 tantalum stents were implanted into the iliac arteries of New Zealand white rabbits for up to 30 weeks. After killing the animals, the specimens were harvested, fixed in formalin, processed in paraffin, and stained. RESULTS: Polyhydroxybutyrate instigated intense inflammatory and proliferative reactions with an increase in collagen (2.4- to 8-fold vs native segments), thrombosis and in-stent lumen narrowing (375.5-606.6 mm vs 655.6 +/- 268.8 mm in native segments). The elastic membranes were destroyed in all specimens. The tantalum stents increased the in-stent lumen progressively (769.7 +/- 366.6 mm vs 1309.9 +/- 695.3 mm), penetrated the external elastic membrane, and increased mural collagen content (6- to 8.6-fold vs native segments). Neither restenoses nor thromboses occurred. CONCLUSIONS: In the rabbit iliac artery, polyhydroxybutyrate stents caused intensive inflammatory vascular reactions which ban them from clinical use.

[First results in an animal model on stents sheathed with a polytetrafluoroethylene membrane]. / Erste tierexperimentelle Ergebnisse eines von einer Polytetrafluoroethylenmembran umhüllten Koronarstents.

OBJECTIVES: Mechanisms of restenosis after coronary stent implantation include marked intimal proliferation as well as vascular tissue protrusion through the meshes. Thus, stent sheathed with membranes may be an alternative to improve the long-term outcome. METHODS: Seventeen cylindric serpentine shaped 316L stainless steel stents (nominal diameter 3.0 mm, length 15 mm) lined and covered by a polytetrafluoroethylene (PTFE) membrane and 10 unsheathed devices were implanted into the iliac arteries of 14 New Zealand White Rabbits for an observation period of 1 - 10, 11 - 20, and 21 - 30 weeks. After sacrificing the animals, specimens were harvested, fixed in formalin, processed in paraffin, serially sliced into 5 microm thick preparations, and stained (hematoxylin & eosin, elastica von Gieson). RESULTS: The polytetrafluoroethylene membrane stents increased the vascular lumen significantly (p < 0.04) to 1185.3 - 1620.4 microm compared with the native segments (655.6 +/- 268.8 microm). In the stainless steel stents the lumen decreased from 1873.1 microm to 719.1 microm. None of the devices penetrated the internal elastic membrane. There was no inflammatory vascular reaction. Compared to the native segments, the amount of elastic fibres was slightly less (native: 8.9 %, PTFE: 2.3 - 3.5 %, without PTFE: 1.9 - 5.5 %) whereas the collagen fibres increased marginally (native: 5.1 %, PTFE: 6 - 6.9 %, without PTFE: 6.4 - 8.4 %). CONCLUSIONS: In the rabbit iliac artery, stents sheathed with a microporous polytetrafluoroethylene membrane showed good tissue compatibility with no restenosis. These results warrant clinical trials.

[Evaluation of authorised experiments on laboratory animals with regard to the aim of the research to be carried out, its scientific usefulness and its medical relevance]. / Evaluation von genehmigten tierexperimentellen Versuchsvorhaben in Bezug auf das Forschungsziel, den wissenschaftlichen Nutzen und die medizinische Relevanz.

As a follow-up to our recent study about the suffering of laboratory animals in experiments, we investigated if results obtained from animal experiments performed in accordance with the German animal welfare act were published, and if these led to consequences in the medical field, especially in published medical literature. According to the German animal welfare act animal experiments must be applied for at a local ethics committee which approves these experiments. All applications (51) made between 1991 and 1993 were examined in co-operation with some of the authors and the authorities. The follow-up procedures were split into two parts: First the declared aims of the proposals were evaluated against the applicants" own arguments with regard to the pain suffered by the animals. Secondly, it was evaluated if these proposals led to relevant publications in the scientific literature and if these results led to improvements in respective fields of research. A ranking was established from zero (no results were published within 8 years) to three (all the proposed goals were effectively reached and published). Only one third of the proposals reached grade three, and in nearly 40% of the proposals either no relevant publications were found or these proposals were never realised. Differentiation of the research in applied and basic research revealed that basic research per se results in a much higher percentage of grade three (over 56%). No research was done whether or not the scientific findings were applied to humans. Further details were evaluated: 1. In comparison to regulations proposed by the Swiss Veterinarian Inspectorate (BVET), in nearly 60% of the cases the suffering of the animals was underestimated. 2. In some cases despite negative results in animal experiments this research led to successful application in the treatment of human diseases 3. The research leading to grade three was predominantly done on mice and rats. 4. An evaluation of the competence of persons performing experiments was made with respect to legislation. Exceptions to these rules were investigated. 5. Some particular results obtained by the authors as well as their scientific argumentation were evaluated by comparison with all the information available in the current literature and in the light of ethical considerations. We came to the conclusion that all argumentations and justifications to perform animal experiments for the exploration of new drugs, new surgical techniques and new biomaterials must be evaluated and justified much better before any animal experiment can be started.

Experimental model for transplantation of a modified free myocutaneous gracilis flap to an irradiated neck region in rats.

In 102 Wistar rats (male, weight 300-500 g), a modified free myocutaneous gracilis flap was obtained from the groin and transplanted to the neck. To create a pre-irradiated transplant bed, a local area of the neck was irradiated preoperatively with 30 Gy (fractionation: 3 x 10 Gy) in 30 animals, and with 50 Gy (fractionation: 5 x 10 Gy) in a further 30 animals. The interval between preoperative irradiation and transplantation was 4 weeks. Forty-two animals received no such preoperative radiation. The evaluation of healing and the success of the transplanted flap was based on a clinical assessment, carried out on postoperative days 1 7. Testing for significant differences was done nonparametrically using the Kruskal-Wallis test. The survival rate in the nonirradiated animals was 86%. In contrast, the healing of the free flaps in the pre-irradiated transplant bed was significantly lower (P=0.003) 76%, after irradiation with 30 Gy and 50% after 50 Gy. The significant difference (P=0.020) in survival rates after irradiation with 30 and 50 Gy was evidence for the dependence of successful healing on the preoperative radiation dose. Transplantation of the free myocutaneous gracilis flap to a previously irradiated transplant bed in the region of the neck is a suitable model for investigating the healing of free transplants to irradiated tissue. The success rate observed in non-irradiated transplant beds is comparable to that seen with other flap models in rats.

Improved technique for cannulation of the murine thoracic duct: a valuable tool for the dissection of immune responses.

Several experimental approaches have been used in the past for the cannulation of the thoracic duct in mice. Most, however, are characterized by a modest reproducibility and a low lymph yield. Here, we describe a cannulation technique modified with respect to the anesthesia, the use of a silicone cannula and a simple and efficient intraabdominal fixation of the drain. Surgery averaged 45 min with an intra- and postoperative mortality rate of zero. Postoperatively, mice were given access to an exercise wheel allowing increased mobility and consequently a good lymph flow, thus maintaining the function of the cannula. The mice yielded a mean of 29.3 ml/24 h (range 8-40 ml) thoracic duct lymph, which contained a mean of 2.2 x 10(6) lymphocytes/ml during the first 24 h, decreasing to 0.1 x 10(6) lymphocytes/ml on the 2nd day after cannulation. Patency of the cannulae was 100% after 3 days. Interestingly, we have detected strain dependent differences in the anatomy of the thoracic duct in the mouse and these need to be considered when cannulation procedures are attempted.