Sheep models for evaluation of novel patch and prosthesis material in vascular surgery: tips and tricks to avoid possible pitfalls

Abstract

BackgroundIn vascular surgery, novel synthetic prosthesis materials for patch-angioplasties, interpositions, bypasses and shunts are continuously under development and optimization. The characteristics of an ideal vascular prosthesis would display long-term patency, biocompatibility, durability, low porosity, lack of stich hole bleeding, ease of handling, kink resistance, infection resistance and reasonable costs. The aim of this study was to establish and report a reliable sheep model including potential pitfalls where those parameters could be analyzed. Before surgery, sheep were acclimatized for 4–8 weeks, during which parasite infections were treated and blood and serum parameters monitored. Twenty-four sheep underwent surgery, and carotid patch-angioplasties (n = 12), graft interpositions (n = 6) or arteriovenous prosthetic shunts (n = 6) were implanted. Half of the animals in each group were sacrificed after 2 weeks and the other half after 8 weeks. The implants were analyzed for patency, endothelialization, thrombogenicity and biocompatibility by clinical observation, blood flow measurement and pathological and histopathological (H&E, EvG) as well as immunohistochemical (Ki67, CD31) evaluations.ResultsHealth monitoring of the sheep revealed a parasitic burden with endoparasites in all animals. Some animals showed thereby infestations in the bile duct causing fibrotic cholangitis with calcifications in the liver. In addition, sarcosporidia were detected in histopathological specimen of the heart in all animals. Parasitic burden correlated with blood counts and serum bilirubin levels. Both were significantly reduced by albendazole treatment within the acclimatization time. Patches, interposition grafts, and straight shunts were successfully implanted bilaterally in all animals. The total average operation time was 136 ± 21 min. Most animals (23/24) showed good patency rates and general condition after implantation. Pathological and histopathological/immunohistochemical analyses were suitable to determine thrombogenicity, endothelialization, cellular/fibroblastic proliferation, biocompatibility, inflammatory cell infiltration, and thickness of neointima in the prosthesis material.ConclusionsWe have developed a suitable experimental protocol with standardized and successful anesthesia- and surgical-procedures for patch-angioplasty, graft interposition, and arteriovenous prosthetic shunts. This sheep model allows testing of new prosthetic materials for biocompatibility, thrombogenicity, and endothelialization.

A Novel Hybrid Silk Fibroin/Polyurethane Arteriovenous Graft for Hemodialysis: Proof‐of‐Concept Animal Study in an Ovine Model

“…Although these findings cannot be directly translated to the human case, the selected animal model confirmed to be suitable to recapitulate the histopathological patterns of vascular access failure in humans, characterized by venous outflow stenosis resulting from intimal hyperplasia at the venous anastomosis. [12,22,26] Herewith, intimal hyperplasia was indeed detected, and found to increase in thickness between day 30 and day 90, especially at the arterial/venous anastomoses ( Figure 6). However, a tendency of the IH thickening to slow down between day 60 and day 90 was noted on the venous side (V1-V4, Figure 6L), and the regime IH thickness in all the subjects was slight to minimal (<500 µm), and considerably lower as compared to values found with ePTFE grafts in similar animal models (>800 µm).…”

Surgical removal of part of an occluder to treat iatrogenic coarctation of the aorta: a case report

“…It is preferred over the bovine patch because of the following reasons: First, the patch is wrapped outside the vessel and not in direct contact with blood. Thus, the characteristics of an ideal vascular prosthesis, such as puncture-free bleeding, need not be considered [18]. Second, calcification may occur in the bovine patch [19], and consequently its protective effect may disappear.…”

In vivo endothelialization and neointimal hyperplasia assessment after angioplasty of sheep carotid artery with a novel polycarbonate polyurethane patch

“…Preoperative care, premedication, and anesthesia were performed in the same manner as previously published in detail: the animals were premedicated intramuscularly with a premixed solution of 0.16 mg/kg Atropin (1% solution) and 0.2 mg/kg Xylazin (2% solution). 15 General anesthesia was maintained with 1.5 vol% Isoflurane inhalation and intravenous infusion of 0.02 mg/kg/h Fentanyl. An intravenous prophylactic dose of cefuroxime (1.5 g Cefuroxime, Fresenius Kabi Deutschland GmbH, Bad Homburg, Germany) was administered immediately before surgery.…”

“…A longitudinal arteriotomy was performed, the lumen of the carotid artery was rinsed with heparinized saline, and the arteriotomy was closed by patch angioplasty: the patch (6 mm width × 6 cm length) was soaked in heparinized saline solution (10,000 IU/200 ml) for at least 5 min prior to implantation and was sewn in with a 6.0 polypropylene running suture (Prolene 6–0 TF1, Johnson & Johnson Medical GmbH, Norderstedt, Germany) (Figure 2). 15 Sheep display a tendency to hypercoagulability. Therefore, a second dose of heparin (2500 IU) was given to all animals intravenously before clamping the carotid artery of the opposite side, which was operated in the same manner.…”