Table 1.

Overview of model studies investigating the effects of radiation and/or fluid shifts on the cardiovascular system.

Author	Model	Exposure	Results
Spaceflight radiation
Yan et al.⁹³	Male C57Bl/6NT mice; age: 8-10 mo	Single dose IR: Iron (⁵⁶Fe 0.15Gy, 1 GeV/n) and proton (¹H; 0.5 Gy, 1 GeV); WBE	↓ systolic and diastolic function 1 mo post-IR ↑ cardiac hypertrophy 3 mo post-IR ↑ cardiac inflammatory marker infiltration 3 mo post-IR ↓ calcium handling
Sasi et al.⁹⁴	Male C57Bl/6NT mice; age: 8-9 mo	Multiple dose IR: 0.15Gy ⁵⁶Fe →+ 3 × ⁵⁶Fe + ¹H; WBE	↑ cardiac hypertrophy 1 mo post-IR ↓ diastolic function 1 mo post-IR ↓ NFATc4 activity 3 mo post-IR
Seawright et al.⁹⁵	Male C57Bl/6J mice; age: 6 mo	Single dose IR: ¹⁶O 0.1-1.0Gy, 600 MeV/n; WBE	↑ cardiac hypertrophy 2 mo post-IR ↓ systolic function 3 mo post-IR ↑ cleaved caspase-3 activity 3 mo post-IR ↑ cardiac immune markers 3 mo post-IR
Koturbash et al.	Male C57BL/6J mice; age: 10 wks	Single dose IR: ⁵⁶Fe 0.5 Gy ; WBE	DNA hypermethylation 90 days post-IR
Grabham et al.⁹⁶	HUVEC	⁵⁶Fe 1 Gy	↓ vasculogenesis
Fluid shift
Wang et al.⁵³	Male Sprague Dawley rats; age: NR	6 wks HLU	↓ systolic and diastolic function ↓ cardiac mass ↓ cardiomyocyte contractile function ↓ cardiomyocyte glucose utilization
Liang et al.⁵⁵	Male C57BL/6 mice; age: 2 mo	14 or 28 days HLU	↓ systolic function ↓ cardiac mass ↑ cardiac ROS ↑ calpain
Respress et al.⁴⁷	C57Bl/6 mice (sex NR), age: NR	28 days HLU	↓ systolic function ↑ pacing-induced ventricular arrhythmias ↑ frequency of spontaneous sarcoplasmic reticulum calcium release events ↑ sarcoplasmic reticulum calcium leak
Cao et al.⁵⁸	Male C57BL/6N and SJL/JOrlIcoCrl mice; age: 3 mo	28 days HLU	↓ NK cells, B cells, and erythrocyte precursors in the bone marrow
Lui et al.⁴⁹	HL-1 cardiomyocytes	2D clinostat	↑ cytosolic calcium concentration ↑ cardiomyocyte atrophy
Feger et al.⁵⁴	Primary rat neonatal cardiomyocytes	Rotating wall vessel	↓ protein turnover ↔ apoptosis ↑ mitochondrial protein translation
Spaceflight radiation + Fluid shift
Seawright et al.⁹⁷	Female C57BL/6J mice; age: 6 mo	21 days low dose γ-IR (Co-57) WBE + HLU	↑ cardiac ROS relative to IR or HLU alone ↓ cardiac methylation relative to IR or HLU alone
Wnorowski et al.⁸¹	hiPSC-CMs	5.5 wks on ISS	↓ decreased calcium recycling rate ↑ upregulation of sarcomere genes ↓ in DNA damage and repair genes
Camberos et al.⁹⁸	Adult and neonatal cardiac progenitor cells	30 days on ISS	↑ induction of transcripts associated with stemness, cell cycle progression, cell differentiation, heart development, oxidative stress and focal adhesion

Abbreviations: IR, ionizing radiation; Gy, Gray; GeV; gigaelectronvolt; LV, left ventricle; WBE, whole body exposure; HLU, hind limb unloading; NR, not reported; NFATc4, Nuclear Factor Of Activated T Cells 4; HUVEC; Human umbilical vein cells; ROS, reactive oxygen species; hiPSC-CMs, Human induced pluripotent stem cells – derived cardiomyocytes; ISS, International Space Station.