Cardiac Injury after 10 Gy Total Body Irradiation: Indirect Role of Effects on Abdominal Organs

Abstract

The objective of this study was to determine whether radiation-induced injury to the heart after 10 Gy total body irradiation (TBI) is direct or indirect. Young male WAG/RijCmcr rats received a 10 Gy single dose using TBI, upper hemi-body (UHB) irradiation, lower hemi-body (LHB) irradiation, TBI with the kidneys shielded, or LHB irradiation with the intestines shielded. Age-matched, sham-irradiated rats served as controls. The lipid profile, kidney injury, heart and liver morphology and cardiac function were determined up to 120 days after irradiation. LHB, but not UHB irradiation, increased the risk factors for cardiac disease as well as the occurrence of cardiac and kidney injury in a way that was quantitatively and qualitatively similar to that observed after TBI. Shielding of the kidneys prevented the increases in risk factors for cardiac disease. Shielding of the intestines did not prevent the increases in risk factors for cardiac disease. There was no histological evidence of liver injury 120 days after irradiation. Injury to the heart from irradiation appears to be indirect, supporting the notion that injury to abdominal organs, principally the kidneys, is responsible for the increased risk factors for and the occurrence of cardiac disease after TBI and LHB irradiation.

Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS

“…The observations of significant pathology at these relatively low radiation doses, compared to those used in partial body exposure models that focus high dose exposures on specific organs while sparing of bone marrow and GI, may reflect multi-organ interactions, such as have been reported between kidney and heart (Lenarczyk et al 2013). The C57BL/6 mouse H-ARS model thus appears to be an appropriate model for some aspects of DEARE, and potentially valuable for the assessment of mitigators on H-ARS survival as well as DEARE.…”

“…Our observations of pericardial, myocardial, and perivascular fibrosis are consistent with these previous reports in animals and also of clinical studies (Little et al 2012) (Shimizu et al 2010) (Robert Stewart and Fajardo 1984, Veinot and Edwards 1996, Virmani et al 1999, Ivanov et al 2006). The role of renal dysfunction on cardiovascular pathology (Adams et al 2012, Lenarczyk et al 2013, Sera et al 2013) and of microvascular injury (Fajardo and Stewart 1971, Yarom et al 1993, Baker et al 2009, Seemann et al 2012) and Nox2 (Johar et al 2006, Bache and Chen 2014, Murdoch et al 2014) in the fibrotic response subsequent to whole body irradiation are among the questions that require more investigation.…”

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

“…At lower doses (0.5-5 Gy), in humans and in in vivo and in vitro experiments, many inflammatory markers are upregulated long after exposure to radiation, although for exposures less than about 0.5 Gy, the balance shifts toward anti-inflammatory effects [9,28,30], implying that the initiating mechanisms for adverse effects in this dose range would not directly result from inflammation. A recent analysis of death from renal failure in the Life Span Study suggests that radiation-induced renal dysfunction may be a factor in increasing the risk of circulatory disease [31], and some experimental data support this suggestion [32].…”

Low dose radiation and circulatory diseases: a brief narrative review

“…There is nevertheless suggestive evidence for radiation-induced endothelial cell senescence and associated monocyte adhesion [51]. There is support for the kidney being the target tissue in relation to hypertension in the LSS cohort [52] and in experimental animal data [53].…”