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

• Published in: International journal of radiation biology Vol. 90; no. 5; pp. 363 - 372
• Main Authors: Moroni, Maria, Elliott, Thomas B., Deutz, Nicolaas E., Olsen, Cara H., Owens, Rossitsa, Christensen, Christine, Lombardini, Eric D., Whitnall, Mark H.
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.05.2014; Taylor & Francis
• Subjects: Animal model; Animals; ARS; blood; Bone Marrow Cells - radiation effects; Gastrointestinal Tract - radiation effects; Hematopoiesis - radiation effects; Inflammation - etiology; Male; minipig; radiation; Radiation Dosage; Radiation Injuries, Experimental - complications; Radiation Injuries, Experimental - metabolism; Radiation Injuries, Experimental - pathology; Radiation Injuries, Experimental - physiopathology; SIRS; Space life sciences; Survival Analysis; Swine; Swine, Miniature; Syndrome; Time Factors
• ISSN: 0955-3002; 1362-3095
• DOI: 10.3109/09553002.2014.892226

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: Moroni et al. 2011a, 2011c), 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.