Age at Exposure to Radiation Determines Severity of Renal and Cardiac Disease in Rats

Lenarczyk, Marek; Kronenberg, Amy; Mäder, Marylou; North, Paula E.; Komorowski, Richard; Cheng, Qing; Little, Mark P.; Chiang, I-Hung; LaTessa, Chiara; Jardine, James; Baker, John E.

doi:10.1667/rr15043.1

Cited by 12 publications

(19 citation statements)

References 26 publications

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“…Irradiations were conducted with orthovoltage X‐rays from an X‐RAD 320 X‐ray unit (Precision X‐Ray Inc, Branford, CT) and a Pantak HF320 orthovoltage system (Therapax, Danbury, CT) at the MCW Radiation Core facility. The radiation dosimetry has been described previously, 17 …”

Section: Methodsmentioning

confidence: 99%

“…To test whether local irradiation of both the kidneys resulted in remodeling of the nontargeted heart in all subsequent studies in WAG and Dahl SS rats, a lateral field was used to irradiate the kidneys avoiding irradiation of the liver and intestines. Conscious rats were immobilized in acrylic plastic jigs during irradiation with parallel‐opposed lateral fields that included both the kidneys 17 . The adrenals were also exposed to radiation.…”

Section: Methodsmentioning

confidence: 99%

“…The X-ray machine was operated at 300 kVp with a half-value layer of 1.4 mm copper. The need to use bone marrow transplantation in animals that received TBI, which was used in a previous study, 17 was avoided by shielding the bone marrow in one leg using a 1/3 inch thickness lead plate. This had no effect on the progression of cardiac injury.…”

Section: Posterior-anterior Irradiationmentioning

confidence: 99%

“…Conscious rats were immobilized in acrylic plastic jigs during irradiation with parallel-opposed lateral fields that included both the kidneys. 17 The adrenals were also exposed to radiation. The rest of the body was shielded using a 1/3 inch thickness lead plate.…”

Section: Lateral Irradiationmentioning

confidence: 99%

“…Systemic blood pressure in trained and conscious rats was measured using a tail pressure cuff as described elsewhere. 17…”

Section: Systemic Blood Pressurementioning

confidence: 99%

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Irradiation of the kidneys causes pathologic remodeling in the nontargeted heart: A role for the immune system

et al. 2020

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Cardiac disease is a frequent and significant adverse event associated with radiotherapy for cancer. Identifying the underlying mechanism responsible for radiation injury to the heart will allow interventions to be developed. In the present study, we tested if local kidney irradiation results in remodeling of the shielded, nontargeted heart. One kidney, two kidneys, or the total body of male WAG and Dahl SS rats were irradiated with 10 Gy of X-rays. Local kidney irradiation resulted in systemic hypertension, increased BUN, infiltration of T lymphocytes, natural killer cells, and macrophages into the renal cortex and medulla, and renal fibrosis. Local irradiation of kidneys in WAG rats resulted in remodeling in the nontargeted heart after 120 days, manifested by perivascular fibrosis and increased interventricular septal thickness, but was not seen in Dahl SS rats due to a high baseline level of fibrosis in the sham-irradiated animals. Genetic depletion of T cells mitigated the nephropathy after local kidney irradiation, indicating a role for the immune system in mediating this outcome. Local kidney irradiation resulted in a cascade of pro-inflammatory cytokines and low-molecular weight metabolites into the circulation associated with transmission of signals resulting in pathologic remodeling in the nontargeted heart. A new model is proposed whereby radiation-induced cardiac remodeling in susceptible animals is indirect, with lower hemi body organs such as the kidney exporting factors into the circulation that cause remodeling outside of the irradiated field in the shielded, nontargeted heart. This nontargeted effect appears to be mediated, in part, by the immune system.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Posterior-anterior Irradiationmentioning

confidence: 99%

Section: Lateral Irradiationmentioning

confidence: 99%

“…Systemic blood pressure in trained and conscious rats was measured using a tail pressure cuff as described elsewhere. 17…”

Section: Systemic Blood Pressurementioning

confidence: 99%