Study on Damage of Myocardial Tissue Under Low-Dose Heart Irradiation in Rats

Abstract

<h3>Purpose/Objective(s)</h3> Radiation induced heart damage (RIHD) is an important late toxicity of thoracic radiotherapy, which is closely relating with the fractional dose of radiotherapy. With the wide application of stereotactic body radiotherapy and hyperfractionated radiotherapy, the single dose and biological equivalent dose (BED) of the heart of exposure have increased when comparing with conventionally fractionated radiotherapy. However, the mean cardiac dose (MHD), which is frequently used clinically to ensure the control of cardiac damage, is continuously decreased to 26 Gy, 20 Gy, etc. There is still controversy about how much dose could control heart radiation damage better. In this study, 15 Gy/3f low-dose irradiation of the whole heart of rats, which BED is similar with 24 Gy/12f irradiation, is selected to explore the possibility and characteristics of RIHD occurrence, and explore the effect of combined recombinant human endostatin on myocardial damage. <h3>Materials/Methods</h3> 75 SD adult male rats were randomly divided into control (C group, E group, MHD₂₅ group) and experimental group (MHD₁₅ group, MHD_15+E group). The irradiation method was single dose 5 Gy/f, once per day, continuous irradiation 3d or 5d. After the irradiation, the E group and MHD_15+E group were given recombinant human endostatin 6mg/kg intraperitoneal injection, once per day, for 14 consecutive days. At 1, 3, and 6 months after intervention, 5 rats in each group were randomly selected for HE, Masson, and immunohistochemical CD34 microvessel staining, and Western Blot detected mitochondrial Complex II protein expression. Two-way ANOVA statistics. <h3>Results</h3> Compared with C group, edema and disorder of myocardial cells, infiltration of inflammatory cells and decrease of microvessel density was observed at 1 month after intervention in HE staining in MHD₁₅ and MHD_15+E group. The expression of complex II protein decreased at 6 months, and the degree of decrease was less than that in MHD₂₅ group (positive control group) (<i>P</i> < 0.05). The microvessel density was further decreased compared with 1 month. Myocardial fibrosis induced by 15 Gy/3f low-dose irradiation of SD rat heart mainly occurred at 6 months, which observed myocardial cord or reticular fibrosis and collagen deposition. Semi-quantitative analysis of myocardial collagen volume fraction CVF significantly increased (<i>P</i> < 0.001) in HE and Masson staining. Details is shown in the table below. Compared with C group, E group observed myocardial edema and decreased microvessel density. There was no significant difference between MHD₁₅ and MHD_15+E group. <h3>Conclusion</h3> Low dose irradiation of 15 Gy/3f (BED = 40 Gy) still cause myocardial fibrosis and damage of cardiac function in SD rats. RIHD were observed after 6 months, which was equal to about 1/5 of the rat's life span, and the time was delayed when compared with the time of RIHD caused by high dose irradiation. Cardiotoxicity was not increased significantly combining recombinant human endostatin on the basis of low-dose cardiac.