Vascular access port implantation and serial blood sampling in a Gottingen minipig (Sus scrofa domestica) model of acute radiation injury

Abstract

Threats of nuclear and other radiologic exposures have been increasing, but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. Because of their similarity to humans in regard to physiology and anatomy, we are characterizing Gottingen minipigs as a model to aid the development of radiation countermeasures. Irradiated minipigs exhibit immunosuppression, severe thrombocytopenia, vascular leakage, and acute inflammation. These complications render serial acquisition of blood samples problematic. Vascular access ports (VAP) facilitate serial sampling, but their use often is complicated by infections and fibrin deposition. We demonstrate here the successful use of VAP for multiple blood samplings in irradiated minipigs. Device design and limited postoperative prophylactic antimicrobial therapy before irradiation were key to obtaining serial sampling, reducing swelling, and eliminating infection and skin necrosis at the implantation site. Modifications of previous protocols included the use of polydioxanone sutures instead of silk; eliminating chronic port access; single-use, sterile, antireflux prefilled syringes for flushing; strict aseptic weekly maintenance of the device, and acclimating animals to reduce stress. VAP remained functional in 19 of 20 irradiated animals for as long as 3 mo. The remaining VAP failed due to a small leak in the catheter, leading to clot formation. VAP-related sepsis occurred in 2 minipigs. Blood sampling did not cause detectable stress in nonanesthetized sham-irradiated animals, according to leukograms and clinical signs.

Figure 1.

Specifications of VAP model used in the current study.

Figure 2.

Histologic examination of the skin and subcutis surrounding VAP in minipigs. (A) Haired skin and subcutis. The position of the VAP (*) is bounded by an immediate layer of granulation tissue and further surrounded by dense strata of fibrous connective tissue and fibrosis. Hematoxylin and eosin stain; magnification, ×20. (B) Layer of granulation tissue composed of reactive fibroblasts, histiocytes, hemosiderophages, lymphocytes admixed with loose collagen, and small caliber vessels (arrows) immediately adjacent to the VAP. Hematoxylin and eosin stain; magnification, ×400. (C) Organized, undulating strata of fibrous connective tissue with regularly spaced small caliber capillaries and fibroblasts. Hematoxylin and eosin stain; magnification, ×400. (D) Gradations of fibroplasias (blue), which increase in density as distance from the VAP increases, compared with the paler blue of the loose collagen admixed with increased density of small and loose capillaries near the surface of the wound. Masson trichrome stain; magnification, ×200.