Moroni Maria, Coolbaugh Thea V, Mitchell Jennifer M, Lombardini Eric, Moccia Krinon D, Shelton Larry J, Nagy Vitaly, Whitnall Mark H
Radiation Countermeasures Program, Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
J Am Assoc Lab Anim Sci. 2011 Jan;50(1):65-72.
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.
核辐射及其他放射暴露的威胁日益增加,但尚无针对急性放射综合征的对策获监管部门批准。由于 Göttingen 小型猪在生理和解剖方面与人类相似,我们将其作为一种模型进行特性研究,以辅助放射对策的研发。受辐照的小型猪会出现免疫抑制、严重血小板减少、血管渗漏和急性炎症。这些并发症使得连续采集血样存在问题。血管通路端口(VAP)便于连续采样,但使用时常常因感染和纤维蛋白沉积而变得复杂。我们在此证明了 VAP 在受辐照小型猪多次血样采集方面的成功应用。设备设计以及辐照前有限的术后预防性抗菌治疗对于实现连续采样、减轻肿胀、消除植入部位的感染和皮肤坏死至关重要。对先前方案的修改包括使用聚二氧六环酮缝线而非丝线;取消长期端口接入;使用一次性、无菌、防回流预充式注射器进行冲洗;严格每周对设备进行无菌维护,以及使动物适应环境以减轻应激。20 只受辐照动物中有 19 只的 VAP 长达 3 个月保持功能正常。其余的 VAP 因导管出现小渗漏导致形成凝块而失效。2 只小型猪发生了与 VAP 相关的败血症。根据血常规和临床体征,血样采集在未麻醉的假辐照动物中未引起可检测到的应激反应。