Accelerated hematopoietic syndrome after radiation doses bridging hematopoietic (H-ARS) and gastrointestinal (GI-ARS) acute radiation syndrome: Early hematological changes and systemic inflammatory response syndrome in minipig

Abstract

Purpose: To characterize acute radiation syndrome (ARS) sequelae at doses intermediate between the bone marrow (H-ARS) and full gastrointestinal (GI-ARS) syndrome.

Methods: Male minipigs, approximately 5 months old, 9–12 kg in weight, were irradiated with Cobalt-60 (total body, bilateral gamma irradiation, 0.6 Gy/min). Endpoints were 10-day survival, gastrointestinal histology, plasma citrulline, bacterial translocation, vomiting, diarrhea, vital signs, systemic inflammatory response syndrome (SIRS), febrile neutropenia (FN).

Results: We exposed animals to doses (2.2–5.0 Gy) above those causing H-ARS (1.6–2.0 Gy), and evaluated development of ARS. Compared to what was observed during H-ARS (historical data: ), doses above 2 Gy produced signs of increasingly severe pulmonary damage, faster deterioration of clinical conditions, and faster increases in levels of C-reactive protein (CRP). In the range of 4.6–5.0 Gy, animals died by day 9–10; signs of the classic GI syndrome, as measured by diarrhea, vomiting and bacterial translocation, did not occur. At doses above 2 Gy we observed transient reduction in circulating citrulline levels, and animals exhibited earlier depletion of blood elements and faster onset of SIRS and FN.

Conclusions: An accelerated hematopoietic subsyndrome (AH-ARS) is observed at radiation doses between those producing H-ARS and GI-ARS. It is characterized by early onset of SIRS and FN, and greater lung damage, compared to H-ARS.

Keywords::

• Animal model
• minipig
• ARS
• radiation
• SIRS
• blood

Acknowledgements

This work was supported by funding from the National Institute of Allergy and Infectious Diseases OD-0505-01 and the Armed Forced Radiobiology Research Institute (AFRRI) RBB2DG. The opinions or assertions contained herein are the private views of the authors and are not necessarily those of AFRRI, the Uniformed Services University of the Health Sciences, or the Department of Defense. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Special thanks are due to AFRRI's Cobalt facility and the Veterinary Sciences Department staff for their dedication to the project and superb animal care.

Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.