Abstract

Purpose

Current animal models of hematopoietic-acute radiation syndrome (H-ARS) are resource intensive and have limited translation to humans, thereby inhibiting the development of effective medical countermeasures (MCM)s for radiation exposure.

Materials and methods

To improve the MCM pipeline, we developed models of H-ARS in male Göttingen and Sinclair minipigs. Weight matched Göttingens and Sinclairs received total body irradiation (TBI; 1.50–2.10 Gy and 1.94–2.90 Gy, respectively), were observed for up to 45 days with blood collections for clinical pathology analysis, and were examined during gross necropsy.

Results

The lethal dose for 50% of the population over the course of 45 days (LD_50/45) with ‘field’ supportive care (primarily antibiotics and hydration support) and implanted vascular access ports was 1.89 and 2.53 Gy for Göttingens and Sinclairs, respectively. Both minipig strains exhibited prototypical H-ARS characteristics, experiencing thrombocytopenia and neutropenia, and nadirs approximately 14 days following irradiation, slightly varying with dose. Both strains experienced increased bruising, petechia, and signs of internal hemorrhage in the lungs, GI, heart, and skin. All observations were noted to correlate with dose more closely in Sinclairs than in Göttingens.

Conclusion

The results of this study provide a template for future MCM development in an alternate species, and support further development of the Göttingen and Sinclair minipig H-ARS models.

中文翻译：

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在哥廷根和辛克莱小型猪中开发和比较造血急性辐射综合征模型

摘要

目的

目前的造血急性辐射综合征 (H-ARS) 动物模型资源密集，对人类的转化有限，从而抑制了针对辐射暴露的有效医学对策 (MCM) 的开发。

材料和方法

为了改进 MCM 管道，我们在雄性 Göttingen 和 Sinclair 小型猪中开发了 H-ARS 模型。体重匹配的 Göttingens 和 Sinclairs 接受了全身照射（TBI；分别为 1.50-2.10 Gy 和 1.94-2.90 Gy），观察长达 45 天，采集血液进行临床病理学分析，并在大体尸检期间进行检查。

结果

_{Göttingens 和 Sinclairs 在 45 天 (LD 50/45} ) 的“现场”支持治疗（主要是抗生素和水合作用支持）和植入血管接入端口的过程中，50% 人口的致死剂量分别为1.89 和 2.53 Gy . 两种小型猪菌株都表现出典型的 H-ARS 特征，经历了血小板减少和中性粒细胞减少，并且在照射后约 14 天达到最低点，随剂量略有不同。两种菌株的肺、胃肠道、心脏和皮肤的瘀伤、瘀点和内出血迹象都增加了。注意到所有观察结果在辛克莱比在哥廷根更密切地与剂量相关。

结论

这项研究的结果为未来在替代物种中的 MCM 开发提供了模板，并支持 Göttingen 和 Sinclair 小型猪 H-ARS 模型的进一步开发。