Experimental Model of Cardiotoxicity

*Oytun Erbaş, İlknur Altuntaş, Özge Çağlar, Elif Özyilmaz, Ece Sari, İlayda Üzümcü and Kaan Erbakan*

### **Abstract**

The occurrence of heart electrophysiology dysfunction or/and muscle damage is referred to as cardiotoxicity. The heart weakens and becomes less efficient at pumping and hence circulating blood. Cardiomyopathy can be caused by a variety of factors, including viral infections, diseases such as diabetes, ischemia, hypertension, obesity, radiation therapy, antipsychotic drugs, cytotoxic drugs, most notably chemotherapeutic agents; antitumor antibiotics, monoclonal antibodies, tyrosine kinase inhibitors, platinum-based compounds, microtubule inhibitors, vinca alkaloids, antimetabolites, proteasome inhibitors, topoisomerase inhibitors, alkylating agents, corticosteroids. This chapter focuses on the mechanisms of cardiotoxicity, animal models and transgenic methods used in studies, and the effects of therapeutic agents on cardiotoxicity.

**Keywords:** cardiotoxicity, cardiomyopathy, chemotherapeutics, diabetes, ischemia, radiation therapy, toxicants, transgenic animal models

### **1. Introduction**

Globally, heart disease is responsible for a third of all deaths [1]. Cardiotoxicity occurs when the heart, in whole or in part, is damaged as a result of factors such as obesity, chemotherapy (CT), alcohol exposure, anorexia, neurosis, unconscious drug use, occupational and environmental heavy metal exposure [2–4].

Toxicants impair pumping efficiency by reducing the number of active myocytes, cause oxidative damage and lipid peroxidation, which results in cell swelling, altered Ca2+ homeostasis, and irreversible myocyte injury, alter aerobic metabolism, myocardial conduction, cell membrane function, directly damaged myocardium, and induce vascular changes [5]. They also cause QT interval prolongation and ionic channel blockage, which can lead to syncope and ventricular fibrillation. The heart weakens and becomes less efficient at pumping and thus circulating blood. Because of the high energy demands of the heart, it is susceptible to toxins that interfere with oxygen availability, carbohydrate metabolism, and oxidative phosphorylation [6, 7].

Cardiotoxicity is characterized by cardiac dysfunctions, arrhythmia (changes in heart rhythm), hypotension, tachypnea, edema, heart muscle damage (cardiomyopathy), changes in transmission pathways, and toxic effects on the heart [3]. Cardiotoxicity includes changes in resting cardiac measurements as well as dynamic functional evaluations of the cardiovascular (CV) systems [3, 5, 6]. The formation of oxygen free radicals and calcium overload in myocytes, a deficiency of antioxidant systems such as catalase and superoxide dismutase, and a possible immunological reaction triggered by the drug are the main pathophysiological processes of cardiotoxicity [8]. Acute or subacute heart damage includes changes in the ventricular repolarization phase, the duration of the QT interval, arrhythmias, ischemia, acute heart failure (HF), and myocarditis-pericarditislike syndrome. As a result of chronic (early/late) conditions, patients may have symptoms such as left ventricular (LV) dysfunction, systolic/diastolic impotence, and cardiac death [9, 10].

Cardiotoxicity is a well-known side effect of many cytotoxic drugs that can result in long-term morbidity.
