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DEVELOPMENT OF PEDIATRIC MODEL OF HEMATOPOIETIC ACUTE RADIATION SYNDROME
(H-ARS) AND COUNTERMEASURE TESTING USING THE GÖTTINGEN MINIPIG
Amandeep Kaur, Nagalaxmi Vemalapally, Grant Severson,
Jatinder Gulani, David Bolduc, Maria Moroni
Pages: 75-81
DOI: 10.21175/RadJ.2017.02.017
Received: 10 JAN 2017, Received revised: 10 MAR 2017, Accepted: 15 MAY 2017, Published online:
28 OCT 2017
Abstract |
References |
Full Text (PDF)
There is a pressing need to develop animal models as well as treatment appropriate for age-specific radiation injuries. The minipig represents a promising animal model for testing the effects of radiation on the pediatric population. We subjected piglets, age 6 weeks old (corresponding to less than 2 years old in human), to either sham irradiation or to total body irradiation (60Cobalt 0.6 Gy/min) at hematopoietic doses spanning from 1.6 Gy to 2.0 Gy, and determined the dose-survival relationship and course of radiation injury in the presence of minimal supportive care. The LD50/45 was determined to be 1.83 Gy [CI 1.70 – 1.91]. The course of hematopoietic acute radiation syndrome (H-ARS) in the piglet model resembled that of humans, with four distinct phases namely, prodromal phase, latent phase, manifest illness phase, and recovery or death. Kinetics of blood cell loss such as sudden lymphopenia, decline in neutrophil counts preceded by initial granulocytosis, erythrocytopenia, and thrombocytopenia with a characteristic shoulder followed by partial recovery mimicked the expected radiation-induced changes. Moribund animals were characterized by anorexia, lethargy, fever or hypothermia, bleeding, and dyspnea. Upon euthanasia, animals displayed dose dependent bone marrow hypoplasia and hemorrhages in several organs. Granulocyte colony stimulating factor (G-CSF), a countermeasure approved for H-ARS in humans and effective in adult minipig, was tested in the piglets. Administration of G-CSF enhanced survival by 37.5% and reduced both duration as well as nadir of neutropenia. In conclusion, the minipig provides a practical and feasible animal model for H-ARS and development of radiation countermeasures for the pediatric population. te
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