15–19 Oct 2012
Vietri sul Mare
Europe/Rome timezone

Differential Effects of Full Body Single Low Dose Proton and Iron Radiation on Acute Myocardial Infarct Recovery in Adult Mice

18 Oct 2012, 18:15
15m
Main Hall (Vietri sul Mare)

Main Hall

Vietri sul Mare

oral (15 minutes) Non-Cancer Effects Non-Cancer Effects

Speaker

Dr David Goukassian (Tufts University School of Medicine)

Description

Astronauts are exposed to space radiation (IR). It is important to evaluate the effect of cosmic radiation on cardiovascular (CV) system. Approximately 41% of space radiation is predicted to be HZE particles with 13% being from 56Fe particles. We hypothesized that (1) low-dose space IR-induced biological responses may be long-lasting and are IR type-dependent; and (2) IR may increase CV risks in the aging heart (IR+A) and affect the processes of CV repair after acute myocardial infarct (AMI) (IR+A+AMI). Nine months C57BL6 male mice were irradiated once with proton 0.5Gy/1GeV/n or 56Fe 0.15Gy/1GeV/n. Cardiac function was assessed by echocardiography and hemodynamic measurements. AMI was induced by ligation of left anterior descending (LAD) coronary artery 1-3 months post IR. Cardiac inflammation, apoptosis and fibrosis were evaluated post AMI. In IR+A group, cardiac function was not different among control, proton and 56Fe irradiated mice 1-3 months post-IR. In IR+A+AMI group, mortality was not different among the groups. Compared to control-AMI mice, inflammation was increased similarly in both proton-AMI and 56Fe-AMI mice up to day 7. Between days 7 and 14, inflammation remained the same in proton-AMI mice, whereas it was sharply decreased in the 56Fe-AMI mice. Compared to control-AMI mice, there was a significant (p<0.01) increase in apoptosis in both proton-AMI and 56Fe-AMI mice by 14 days, and was significantly (p<0.03) higher in 56Fe-AMI vs. proton-AMI mice. Four weeks post AMI, proton-AMI mice had better cardiac functional recovery compared to control-AMI and 56Fe-AMI mice; whereas ejection fraction % (EF%) was most decreased in 56Fe-AMI mice (56Fe-AMI vs. proton-AMI: 18 vs. 48 %, p<0.007, vs.  65-70% pre-AMI EF% for all groups). There was a 2-4-fold increase in left ventricular end diastolic pressure (LVEDP - an indicator that heart is not pumping blood well) in 56Fe-AMI vs. Proton-AMI (p<0.04), suggesting that 56Fe-AMI hearts developed cardiac de-compensation. AMI led to small transmural infarct in control-AMI mice, large transmural infarct in 56Fe-AMI and small superficial infarct in proton AMI mice. Our results revealed that low dose full body single proton or 56Fe IR do not affect cardiac function under normal conditions. Further, a single proton IR three months prior to AMI is beneficial, whereas 56Fe IR is deleterious, for AMI recovery, suggesting that low dose HZE particle radiation have long-lasting negative effect on CV risks such as AMI.

Primary authors

Dr David Goukassian (Tufts University School of Medicine) Dr Xinhua Yan (Tufts University School of Medicine)

Co-authors

Dr Juyoung Lee (Steward St. Elizabeth's Medical Center) Prof. Raj Kishore (Northwestern University) Mr Sharath Sasi (Steward St. Elizabeth's Medical Center) Dr Yongyao Yang (Steward St. Elizabeth's Medical Center)

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