An animal paired crossover ePTFE arteriovenous graft model
© Jahrome et al; licensee BioMed Central Ltd. 2010
Received: 5 June 2010
Accepted: 29 November 2010
Published: 29 November 2010
Previously, we developed a porcine model for Arterio Venous Graft (AVG) failure to allow assessment of new access strategies. This model was limited concerning graft length. In the present technical report, we describe a modification of our model allowing the assessment of long AVGs.
In 4 pigs, AVGs of 15 cm length were created bilaterally in a cross-over fashion between the carotid artery and the contralateral jugular vein. Two days (2 pigs) and two weeks (2 pigs) after AV shunting, graft patency was evaluated by angiography, showing all four grafts to be patent, with no sign of angiographic or macroscopic narrowing at the anastomoses sites.
In this modified pig AVG failure model, implantation of a bilateral cross-over long AVG is a feasible approach. The present model offers a suitable tool to study local interventions or compare various long graft designs aimed at improvement of AVG patency.
In the present report, we describe our experience with a modification on the previous model, addressing this limitation, enabling us to implant and study long length AVG.
A total of 4 female Landrace pigs, weighing 56 ± 2.6 kg, received bilateral crossover AVG (Thin-walled, ePTFE grafts without circular reinforcement measuring 5 mm inner diameter and 150 mm in length (W. L. Gore, Flagstaff, AZ, USA) versus ePTFE spiral graft (Tayside Flow Technologies Limited, Dundee, UK) between the carotid artery and the contralateral internal jugular vein. The rationale for using two grafts types was based in the search by Tayside for a suitable animal to test a new spiral flow bypass. Due to the required length of this graft, we decied to modify our exisiting animal model, using our former basic ePTFE graft as a control. Within this small pilot and feasibility study no further data on the different behaviour of the two graft types were collected other than data as presented in the present technical description. The study protocol was approved by the Institutional Review Board for animal experimentation of the University Medical Center Utrecht and conforms to the Guidelines for the Care and Use of Laboratory Animals.
Before the operation and termination, the animals were fasted overnight and premedicated with intramuscular ketamine 10 mg/kg, midazolam 0.4 mg/kg, atropine 0.5 mg, followed by intravenous thiopental sodium 4 mg/kg. After intubation, animals were mechanically ventilated and anesthesia was maintained intravenously with 0.5 mg/kg/h midazolam, 2.5 μg/kg/h sufentanil and 0.1 mg/kg/h pancuronium. The animals were monitored by electrocardiogram and capnography.
Starting 6 days preoperatively, the pigs received acetylsalicylic acid 80 mg/dd orally. Clopidogrel (Sanofi-Synthelabo, Paris, France) 225 mg was added 1 day preoperatively and continued at a dose of 75 mg/day orally until termination. Heparin 100 IU/kg was provided intravenously before arterial or venous vessel manipulation.
After exposure of the surgical site, dissection of the grafts showed satisfactory early surgical changes, no signs of infection, and intact anastomoses in all 4 pigs. Especially there was no kinking or impression of the AVG in the midline. In animal 3 and 4, after a 14 day follow-up, all grafts and adjacent vessels were excised and examined by longitudinal section before immersion in formalin for at least 24 h.
For testing of intervention t the anastomsis site the same approach can be used as recently published by Huijbregts et al. . To introduce a PTA balloon, the graft can be punctured using a standard needle with a Seldinger approach. Subsequently, a 5 or 6 French sheath can be introduced, and being used as the entrance for wires and balloons. Following intervention, the wires and sheath can be removed, and the puncture hole closed by using Prolene 6-0 suture.
Limitations. Even though the number of animals is small, the number seems to be sufficient for the purpose of the study, which is to assess the feasibility of a new surgical approach.
Several approaches can be chosen to study IH in animal models [4, 5]. However, pigs are favorable animals to study cardiovascular disease because of their analogous vascular anatomy, size, and physiology. Furthermore, the rapid intimal hyperplasia formation at the venous anastomosis in our model closely resembles human hemodialysis graft failure [1, 3]. On the other hand, 8 weeks after surgery a 50% patency loss can be expected in this model . The maximum follow-up for this model therefore is recommended to be 4 weeks.
In the near future, this specific model will be used to further elaborate on the spiral flow effect possibly resulting in lower degree of IH formation.
This modified graft model for rapid AVG failure due to neo-intimal response at the venous outflow tract, offers an extended tool to study new graft materials, or to assess new strategies for improved AVG patency using local interventions at the venous anastomosis site.
In this modified pig AVG failure model, implantation of a bilateral cross-over long AV graft between the carotid artery and contralateral jugular vein is a novel and feasible approach. The major advantage as compared to our previous model is that the present configuration allows the study of longer grafts and grafts with various design modifications, such as tapered or reinforced grafts. The present modified model offers a suitable tool to study local interventions or compare various graft designs aimed at improvement of AV graft patency
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