Abstract 14587: Different Sequence of Fractionated Proton and Single Low Dose Iron Radiation Induce Divergent Biological Responses in the Heart
Astronauts will be exposed to ionizing radiation (IR) composed of a spectrum of low-fluence protons (1H) and high charge and energy (HZE) nuclei iron (e.g., 56Fe). During GCR each cell in the body will be traversed by 1H every 3-4 days and HZE nuclei every few months.
The effects of sequential/fractionated low doses of 1H or HZE on cardiovascular system are unknown. Male C57BL/6NT mice of 8-9 month old were evaluated over 3 months: Group 1- control; Group 2 - 1H 17 cGy every 2 days/3 doses; Group 3 - 1H 17 cGy every 2 days/3 doses followed by a single dose of 56Fe 15 cGy 2 days after the last dose of 1H; Group 4 - a single dose of 56Fe 15 cGy/followed by fractionated 1H 17 cGy every 2 days/3 doses 2 days after a single 56Fe-IR; at 1 GeV energy for both ions. Cardiac function, cardiac fibrosis and cardiac remodeling were assessed by echocardiography, hemodynamic measurements, H&E and Trichrome staining.
In IR + Aging group, over 3 months, 1H+1H+1H-IR alone or 1H+1H+1H/56Fe-IR did not induce negative effect on cardiac function or structure. However, in 56Fe-IR/1H+1H+1H-IR, there were several negative CV developments - left ventricular (LV) maximum pressure change was decreased at 1 month, LV end diastolic pressure (EDP) and cardiac fibrosis was increased at 3 months, which was associated with activation of cardiac hypertrophy signaling (NFATc4). These findings are indicative of negative hemodynamic developments in the heart of mice in Group 4. In IR + Aging + AMI (acute myocardial infarct was induced by ligation of left anterior descending artery) group, 1H+1H+1H-IR alone or 56Fe-IR/1H+1H+1H IR did not have significant negative effects at 1 month post-IR and -AMI. However, in 1H+1H+1H/56Fe group there was a 24% increase in post-AMI mortality, significant decreases in LV ESP and EDP and a 35% increase in post-AMI infarct size. These functional changes were associated with significant decreases in the expression of VEGF-A, reduced activation of Akt and Erk1/2 post-AMI.
These findings are indicative of significant negative effects for post-AMI recovery after 1H+1H+1H/56Fe-IR regimen in the surviving fraction of mice in Group 3.These findings emphasize significant mix ion fractionation and sequence-dependent divergent responses in the heart during aging and after ischemic CV event.
Author Disclosures: S.P. Sasi: None. X. Yan: None. J. Lee: None. K. Walsh: Research Grant; Modest; Takeda Pharmaceuticals. R. Kishore: None. D.A. Goukassian: None.
- © 2016 by American Heart Association, Inc.