Abstract
Aims: Irradiation is an effective treatment for tumors but has been associated with cardiac dysfunction. However, the precise mechanisms remain incompletely elucidated. This study investigated the long-term cardiac damage associated with abdominal irradiation and explored possible mechanisms. Methods and Results: Wild-type C57BL6/J mice were divided into two groups: untreated controls (Con) and treatment group receiving 15 Gy of abdominal gamma irradiation (AIR). Both groups received normal feeding for 12 months. The AIR group showed reductions in left ventricular ejection fraction (LVEF), fractional shortening (FS), left ventricular end-diastolic internal diameter (LVID; d), left ventricular end-diastolic volume (LV Vol. diastolic volume (LV Vol; d) and mitral transtricuspid flow late diastolic filling velocity (MV A). It also showed increased fibrosis, reduced conduction velocity and increased conduction heterogeneity. Non-targeted metabolomics showed the differential metabolites were mainly from amino acid metabolism. Further KEGG pathway annotation and enrichment analysis revealed that abnormalities in arginine and proline metabolism, lysine degradation, d-arginine and d-ornithine metabolism, alanine, aspartate and glutamate metabolism, and arginine biosynthesis. Conclusion: Abdominal irradiation causes long-term damage to the non-irradiated heart, as reflected by electrical and structural remodeling and mechanical dysfunction associated with abnormal amino acid biosynthesis and metabolism.
Highlights
Cancer is the leading cause of mortality worldwide (Soerjomataram and Bray, 2021; Sung et al, 2021)
Left ventricular ejection fraction (LVEF), fractional shortening (FS), left ventricular end-diastolic internal diameter (LVID; d), left ventricular end-diastolic volume (LV Vol; d) and mitral transtricuspid flow late diastolic filling velocity (MV A) were reduced and isovolumic relaxation time (IVRT) was increased in the abdominal radiation group compared to the control group
Based on the previous results, our current results suggests that mice from the abdominal irradiation group may have a certain degree of hyperoxidation, which is consistent with the previously reported bystander effect of radiotherapy
Summary
Cancer is the leading cause of mortality worldwide (Soerjomataram and Bray, 2021; Sung et al, 2021). Due to the early diagnosis and timely intervention of cancer treatment in recent years, deaths due to cancer itself have significantly receded, while cardiac disease and damage caused by tumor treatment have clearly become a major cause of non-neoplastic death. Cardiac Damage with Abdominal Irradiation among cancer survivors (Curigliano et al, 2016; Armanious et al, 2018; Li H. et al, 2019; Alvarez-Cardona et al, 2020). Irradiation is an important treatment for cancer. It can exert adverse effects on normal and otherwise healthy tissues and organs, with significant negative impact on prognosis of cancer patients (Schaue and McBride, 2015; Nielsen et al, 2017; Chargari et al, 2019). Its related cardiac damage occurs in both short- and long-term (Groarke et al, 2014; Cao et al, 2021), while the early stages of cardiac dysfunction may be asymptomatic
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