Effective Echocardiography Parameters to Identify Radiation-Induced Heart Disease in the Mouse Model

Abstract

<h3>Purpose/Objective(s)</h3> Radiation-induced heart disease (RIHD) may occur after excessive radiotherapy to thoracic cancer. However, the effect of cardiac irradiation on left ventricle (LV) function is still controversial and no previous studies has evaluated the importance of stroke volume (SV) in RIHD. The hypothesis is that diastolic dysfunction with decreased SV could be potentially effective echocardiography parameters to identify RIHD in the mouse model. <h3>Materials/Methods</h3> C57 mice (n=5-10 per group) were treated with a single heart X-ray radiation for 20Gy or 0Gy. Echocardiography was performed to evaluate changes in LV dimensions and function before radiation and after radiation 4, 8 weeks. Elisa kits were used to detect the level of serum BNP and cTnI. HE, Masson's trichrome and Sirius red staining was utilized to assess cardiomyocytes size and myocardial fibrosis. Data are expressed as mean values (means±SEM). Statistical analyses were performed using the two-way repeated measures ANOVA or one-way ANOVA for multiple comparisons and student's t-test for unpaired two groups. In all statistical analyses, significance was defined as P < 0.05. <h3>Results</h3> The Myocardial histopathology indicated a markably increased cardiac fibrosis area and cardiomyocytes size at 8 weeks after radiation. Echocardiography analyses revealed that SV (27.02±1.131 vs. 41.64±2.021ul, P<0.0001), the LV end-diastolic volume (45.64±5.054 vs. 72.24±3.758ul, P=0.0018), and cardiac output (12.58±0.6669 vs. 19.16±0.9942ml/min, P<0.0002) of the 20Gy-mice have significantly decreased than the 0Gy-mice at 8 weeks. The dead 20Gy-mice had lower SV (22.40±0.6110 vs. 30.48±0.1827ul, P=0.0153) as compared to the survival 20Gy-mice. Moreover, the LV diastolic anterior (1.042±0.05123 vs. 0.8456±0.02860mm, P=0.0398) and posterior (0.8745±0.02558 vs. 0.7701±0.02551mm, P=0.0290) wall thickness of 20Gy-mice also had significantly increased than the 0Gy-mice. However, there were no significant difference of the EF (P>0.05), fraction shortening (P>0.05), heart rate (P>0.05), and LV end-systolic volume (P>0.05) between two groups at all the time points. In addition, the result of Elisa kits showed that serum BNP level (427.3±34.05 vs. 279.8±24.84ng/ml, P=0.0127) of 20Gy-mice was significantly higher than the 0Gy-mice at 8 weeks while cTnI was not significantly changed. <h3>Conclusion</h3> Diastolic dysfunction and decreased SV instead of systolic dysfunction occurs firstly in radiation-induced heart disease, which could be effective indexes to detect cardiac toxicity induced by irradiation.