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

Lenarczyk M, Su J, Haworth ST, Komorowski R, Fish BL, Migrino RQ, Harmann L, Hopewell JW, Kronenberg A, Patel S, Moulder JE, Baker JE - Pharmacol Res Perspect (2015)

Bottom Line: TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis.Simvastatin mitigated these morphological injuries.Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiothoracic Surgery, Medical College of Wisconsin Milwaukee, Wisconsin.

ABSTRACT
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 20 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.

No MeSH data available.


Related in: MedlinePlus

Increased susceptibility of the heart to the stress of ischemia/reperfusion following TBI and its mitigation by simvastatin. Severity of myocardial infarction, recovery of post ischemic LVDP, and post-ischemic leakage of LDH after 10 Gy TBI alone, 10 Gy TBI plus simvastatin (TBI + Sim) (10 mg/kg bw/day) or simvastatin (10 mg/kg bw/day) alone (Sim) compared with age-matched nonirradiated hearts (control). Horizontal line represents the value for age-matched, sham-irradiated hearts. Data shown as means + SD, n = 6/group. *P < 0.05, 10 Gy vs. age-matched, sham-irradiated controls. +P < 0.05, TBI vs. TBI plus simvastatin. #P < 0.05, simvastatin vs. age-matched, sham-irradiated controls. TBI, total body irradiation; LVDP, left ventricular developed pressure; LDH, lactate dehydrogenase.
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fig06: Increased susceptibility of the heart to the stress of ischemia/reperfusion following TBI and its mitigation by simvastatin. Severity of myocardial infarction, recovery of post ischemic LVDP, and post-ischemic leakage of LDH after 10 Gy TBI alone, 10 Gy TBI plus simvastatin (TBI + Sim) (10 mg/kg bw/day) or simvastatin (10 mg/kg bw/day) alone (Sim) compared with age-matched nonirradiated hearts (control). Horizontal line represents the value for age-matched, sham-irradiated hearts. Data shown as means + SD, n = 6/group. *P < 0.05, 10 Gy vs. age-matched, sham-irradiated controls. +P < 0.05, TBI vs. TBI plus simvastatin. #P < 0.05, simvastatin vs. age-matched, sham-irradiated controls. TBI, total body irradiation; LVDP, left ventricular developed pressure; LDH, lactate dehydrogenase.

Mentions: To determine whether simvastatin affects the ability of the heart to withstand an acute stress after TBI with 10 Gy of X-rays, the severity of injury from an induced myocardial infarction was assessed in the isolated perfused heart. TBI increased the severity of myocardial infarction by 21% at 20 and 80 days after irradiation (Fig.6).


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

Lenarczyk M, Su J, Haworth ST, Komorowski R, Fish BL, Migrino RQ, Harmann L, Hopewell JW, Kronenberg A, Patel S, Moulder JE, Baker JE - Pharmacol Res Perspect (2015)

Increased susceptibility of the heart to the stress of ischemia/reperfusion following TBI and its mitigation by simvastatin. Severity of myocardial infarction, recovery of post ischemic LVDP, and post-ischemic leakage of LDH after 10 Gy TBI alone, 10 Gy TBI plus simvastatin (TBI + Sim) (10 mg/kg bw/day) or simvastatin (10 mg/kg bw/day) alone (Sim) compared with age-matched nonirradiated hearts (control). Horizontal line represents the value for age-matched, sham-irradiated hearts. Data shown as means + SD, n = 6/group. *P < 0.05, 10 Gy vs. age-matched, sham-irradiated controls. +P < 0.05, TBI vs. TBI plus simvastatin. #P < 0.05, simvastatin vs. age-matched, sham-irradiated controls. TBI, total body irradiation; LVDP, left ventricular developed pressure; LDH, lactate dehydrogenase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492761&req=5

fig06: Increased susceptibility of the heart to the stress of ischemia/reperfusion following TBI and its mitigation by simvastatin. Severity of myocardial infarction, recovery of post ischemic LVDP, and post-ischemic leakage of LDH after 10 Gy TBI alone, 10 Gy TBI plus simvastatin (TBI + Sim) (10 mg/kg bw/day) or simvastatin (10 mg/kg bw/day) alone (Sim) compared with age-matched nonirradiated hearts (control). Horizontal line represents the value for age-matched, sham-irradiated hearts. Data shown as means + SD, n = 6/group. *P < 0.05, 10 Gy vs. age-matched, sham-irradiated controls. +P < 0.05, TBI vs. TBI plus simvastatin. #P < 0.05, simvastatin vs. age-matched, sham-irradiated controls. TBI, total body irradiation; LVDP, left ventricular developed pressure; LDH, lactate dehydrogenase.
Mentions: To determine whether simvastatin affects the ability of the heart to withstand an acute stress after TBI with 10 Gy of X-rays, the severity of injury from an induced myocardial infarction was assessed in the isolated perfused heart. TBI increased the severity of myocardial infarction by 21% at 20 and 80 days after irradiation (Fig.6).

Bottom Line: TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis.Simvastatin mitigated these morphological injuries.Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiothoracic Surgery, Medical College of Wisconsin Milwaukee, Wisconsin.

ABSTRACT
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 20 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.

No MeSH data available.


Related in: MedlinePlus