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Title: Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20more » and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5] ;  [1] ;  [6]
  1. Medical College of Wisconsin, Milwaukee, WI (United States)
  2. Phoenix Veterans Affairs Health Care System, Phoenix, AZ (United States)
  3. Univ. of Oxford, Oxford (United Kingdom)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Medical College of Wisconsin, Milwaukee, WI (United States); Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI (United States)
  6. Medical College of Wisconsin, Milwaukee, WI (United States); Children's Hospital of Wisconsin, Milwaukee, WI (United States)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Pharmacology Research & Perspectives
Additional Journal Information:
Journal Volume: 3; Journal Issue: 3; Journal ID: ISSN 2052-1707
British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org:
Country of Publication:
United States
60 APPLIED LIFE SCIENCES blood lipids; cardiovascular risk factors; coronary sclerosis; simvastatin; total body irradiation; ventricular function