**3. Radiation therapy-induced cardiotoxicity**

Cardiotoxicity caused by radiation therapy (RT) is not only seen in adults, but also in children. High radiation exposure, being female, higher anthracycline cumulative dose, trisomy 21, and race are all risk factors for cardiotoxicity in children [66]. Since the early 1900s, ionizing radiation therapy has been utilized to treat cancer [67]. Along with medical advancements, the role of imaging modalities in the administration of the treatment process has gradually increased, in addition to surgical and systematic treatment [68, 69]. Considering the significance of these procedures in the treatment process and in enhancing survival, heart problems from radiotherapy remain a risk [69]. Radiation-induced heart disease (RIHD) is an important cause of long-term non-cancer death after thoracic irradiation [70]. Studies have shown that people who live at least 5 years after diagnosis have a high rate of cardiovascular death [71]. Studies have shown that significant cardiovascular events usually occur within 10–15 years [72]. Lung cancer, mediastinal lymphoma, and breast cancer are cancers that are proximal to the heart and have the highest prevalence of RT, which means they have a significant risk of cardiotoxicity [73]. When Saika et al. looked at breast cancer radiotherapy treatment and heart failure risk, they discovered that women who had RT for breast cancer had a 10 times higher risk of heart failure than the control group, regardless of age or cancer type [74]. Cardiotoxicity from RT causes a worsening of cardiac function in a variety of illnesses, including cardiomyopathy, pericardial injury, coronary artery disease, and heart disease [75, 76].

The effects of factors such as the total radiation volume applied to the patient, the patient's age, the radiation exposure process, and the simultaneous use of cardiotoxic chemotherapeutic drugs such as anthracyclines are seen in radiation-induced heart diseases [1, 4]. Symptoms of these diseases include pericardial and myocardial fibrosis, rhythm disorders, conduction abnormalities, atherosclerosis, and heart valve injuries. Although, cardiac issues do not manifest themselves until later in life in people, evidence of cardiac toxicity can be found after 10–15 years of follow-up [1, 77]. It has been stated in the literature that RT may have detrimental effects on several important tissues in the heart [68]. In studies, it has been explained that the basis of the mechanism of cardiac damage caused by RT is related to microvascular changes and inflammation that causes longer-term fibrotic changes [1, 68, 78].

Following are a few examples of *in vivo* models of radiation-induced cardiotoxicity and protective agents based on the literature;

In the studies carried out so far, models have been created with different animals to create experimental animal models of cardiotoxicity. Some of these models are Male Albino rats [79, 80], Male Sprague-Dawley rats [63], Albino Wistar rats [81], male C57/BL6 mice [82].

Mezzaroma et al. used three-month-old C57BL/6J male mice in their study, and 12 of them were irradiated with a single 20 Gray (Gy) dose of radiation therapy, while the other six underwent sham-irradiation. They found that when compared to sham non-irradiated mice, radiation therapy-treated mice exhibited a 2-fold higher rate of myocardial interstitial fibrosis after six months [83].

Using Mast cell-deficient rats (Ws/Ws) and mast cell–competent littermate controls (+/+), researchers exposed the rats for six months to 18 Gy localized singledose irradiation to investigate cardiac function. They found that mast cell–deficient rats had a higher upward/leftward shift in the left ventricular (LV) diastolic pressure-volume relationship, a decrease in vivo LV diastolic area, and a greater rise in the thickness of the LV posterior wall [84].

Dreyfuss et al. in their study aimed to develop a new mouse model to investigate the pathophysiological mechanism of RT-induced cardiotoxicity and to detect clinically targetable biomarkers of cardiac damage. They used 9–11 weeks of female C57BL/6 mice to form the model. Single radiation doses of 20, 40 or 60 Gy were given to the selected mice, with or without the adjacent lung tissue, using conformal radiation therapy to the cardiac apex. When the results were analyzed, perivascular fibrosis was seen 8 and 24 weeks after RT. The developed model can be utilized to incorporate radiomic and biochemical markers of cardiotoxicity to guide early treatment intervention and human translation studies [85].

#### *Experimental Model of Cardiotoxicity DOI: http://dx.doi.org/10.5772/intechopen.101401*

In another study, Ibrahim et al. aimed to detect cardiac magnetic resonance (CMR) imaging markers of early RT-induced cardiac dysfunction. In the study, the effect of CMR on global and regional cardiac function and myocardial T1/T2 values at 2-time points after RT with the use of CMR in a localized cardiac RT rat model was investigated. Rats that received 24 Gy radiation, whole-heart radiation were compared to sham-treated rats. They concluded that MRI regional myocardial strain is sensitive imaging diagnostic for detecting RT-induced subclinical cardiac damage before global cardiac function was compromised [86].
