A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.
A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.
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DOI：
10.1097/hp.0b013e31825f75a7
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发表时间：
2012-10
期刊：
影响因子：
2.2
通讯作者：
MacVittie TJ
中科院分区：
文献类型：
--
作者：
Farese AM;Cohen MV;Katz BP;Smith CP;Jackson W 3rd;Cohen DM;MacVittie TJ
针对急性放射综合征的造血亚综合征的医学对策的发展需要良好表征和验证的动物模型。该模型必须定义死亡率和主要发病体征的辐射剂量和时间依赖关系，以包括可能导致发病率和死亡率的其他器官损伤。在这里，我们定义这些参数的非人灵长类动物暴露于全身辐射和管理的医疗管理。一项设盲、随机化研究（n=48只恒河猴）使用双侧6 MV线性加速器光子辐射以0.80 Gy/min的剂量范围7.20至8.90 Gy确定了致死剂量反应关系。照射后，监测动物的全血细胞计数、体重、体温、腹泻和水合状态60天。对动物进行药物管理，包括静脉输液、预防性抗生素、输血、抗惊厥药、镇痛药和营养。主要终点是照射后60天的生存率;次要终点包括造血相关参数、输血次数、记录的感染发生率、发热性中性粒细胞减少症、腹泻严重程度、死亡者的平均生存时间和组织学。该研究定义了LD 30/60为7.06 Gy，LD 50/60为7.52 Gy，LD 70/60为7.99 Gy，斜率相对较陡，为1.13 probits/线性剂量。本研究建立了恒河猴造血系统急性放射综合征模型，并显示了医疗管理对提高死亡动物的生存率和总平均生存时间的显着作用。此外，在发生核恐怖事件后，医疗管理可能是唯一按最佳时间表实施的治疗。
The development of medical countermeasures against the hematopoietic sub-syndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to the morbidity and mortality. Herein, we define these parameters for the nonhuman primate exposed to total-body radiation and administered medical management. A blinded, randomized study (n=48 rhesus macaques) determined the lethal dose response relationship using bilateral, 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90Gy at 0.80Gy minute−1. Following irradiation animals were monitored for complete blood counts, body weight, temperature, diarrhea, and hydration status for 60 days. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics and nutrition. The primary endpoint was survival at 60 days post irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents and tissue histology. The study defined an LD30/60 of 7.06Gy, LD50/60 of 7.52Gy, and an LD70/60 of 7.99Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.