The dose response relationship and corresponding values for mid-lethal dose and slope are used to define the dose- and time-dependent parameters of the hematopoietic acute radiation syndrome. The characteristic time course of mortality, morbidity, and secondary endpoints are well defined. The concomitant comorbidities, potential mortality, and other multi-organ injuries that are similarly dose- and time-dependent are less defined. Determination of the natural history or pathophysiology associated with the lethal hematopoietic acute radiation syndrome is a significant gap in knowledge, especially when considered in the context of a nuclear weapon scenario. In this regard, the exposure is likely ill-defined, heterogenous, and nonuniform. These conditions forecast sparing of bone marrow and increased survival from the acute radiation syndrome consequent to threshold doses for the delayed effects of acute radiation exposure due to marrow sparing, medical management, and use of approved medical countermeasures. The intent herein is to provide a composite natural history of the pathophysiology concomitant with the evolution of the potentially lethal hematopoietic acute radiation syndrome derived from studies that focused on total body irradiation and partial body irradiation with bone marrow sparing. The marked differential in estimated LD50/60 from 7.5 Gy to 10.88 Gy for the total body irradiation and partial body irradiation with 5% bone marrow sparing models, respectively, provided a clear distinction between the attendant multiple organ injury and natural history of the two models that included medical management. Total body irradiation was focused on equivalent LD50/60 exposures. The 10 Gy and 11 Gy partial body with 5% bone marrow sparing exposures bracketed the LD50/60 (10.88 Gy). The incidence, progression, and duration of multiple organ injury was described for each exposure protocol within the hematopoietic acute radiation syndrome. The higher threshold doses for the partial body irradiation with bone marrow sparing protocol induced a marked degree of multiple organ injury to include lethal gastrointestinal acute radiation syndrome, prolonged crypt loss and mucosal damage, immune suppression, acute kidney injury, body weight loss, and added clinical comorbidities that defined a complex timeline of organ injury through the acute hematopoietic acute radiation syndrome. The natural history of the acute radiation syndrome presents a 60-d time segment of multi-organ sequelae that is concomitant with the latent period or time to onset of the evolving multi-organ injury of the delayed effects of acute radiation exposure.

中文翻译：

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非人类灵长类动物急性辐射诱发的 H-ARS 和伴随的多器官损伤的自然史：MCART 经验。

剂量反应关系以及相应的中致死剂量和斜率值用于定义造血急性辐射综合征的剂量和时间依赖性参数。死亡率、发病率和次要终点的特征时间过程已明确定义。类似的剂量和时间依赖性的伴随并发症、潜在死亡率和其他多器官损伤的定义较少。与致命性造血急性辐射综合征相关的自然史或病理生理学的确定是一个重大的知识空白，特别是在核武器场景的背景下考虑时。在这方面，暴露可能是不明确的、异质的和不均匀的。这些情况预示着骨髓的保护和急性放射综合征的生存率增加，而急性放射综合征的生存率是由于骨髓保护、医疗管理和使用经批准的医疗对策而导致的急性辐射暴露的延迟效应的阈值剂量。本文的目的是提供与潜在致命的造血急性辐射综合征的演变相伴的病理生理学的复合自然史，该综合征源自集中于全身照射和保留骨髓的部分身体照射的研究。5% 骨髓保留模型的全身照射和部分身体照射的估计 LD50/60 分别从 7.5 Gy 到 10.88 Gy 存在显着差异，这提供了两种模型伴随的多器官损伤和自然史之间的明显区别其中包括医疗管理。全身照射集中于等效 LD50/60 暴露。10 Gy 和 11 Gy 局部身体暴露 5% 骨髓保留暴露在 LD50/60 (10.88 Gy) 范围内。描述了造血急性辐射综合征中每个暴露方案的多器官损伤的发生率、进展和持续时间。保留骨髓方案的部分身体照射的较高阈值剂量引起了明显程度的多器官损伤，包括致命的胃肠道急性辐射综合征、长期隐窝丢失和粘膜损伤、免疫抑制、急性肾损伤、体重减轻，并增加了临床合并症通过急性造血急性辐射综合征定义了器官损伤的复杂时间表。急性辐射综合征的自然病程表现为多器官后遗症的 60 天时间段，与急性辐射暴露延迟效应的多器官损伤的潜伏期或发病时间相伴。