Study on the Cardiotoxicity and Ventricular Arrhythmia Susceptibility Induced by Doxorubicin

XU Qianqian; WEI Xiaohong; DAI Qianqian; JIANG Huiru; ZHANG Huamin; SHANG Hongcai

Abstract：Objective To evaluate the occurrence of susceptibility to ventricular arrhythmia after doxorubicin(DOX)-induced acute cardiotoxicity in rats.Methods Twenty Sprague-Dawley rats were randomly divided into a blank group(Control)and a DOX group,with 10 rats in each group.The Control group was intraperitoneally injected with 0.9%sodium chloride solution,and the DOX group was intraperitoneally injected with 15 mg/kg DOX for once to induce acute cardiotoxicity.The general condition of rats in the two groups was observed.Echocardiography and HE staining were used to detect the changes in cardiac function and myocardial tissue pathology of rats.Electrophysiological methods were used to detect the changes in intracardiac electrophysiological indexes and ventricular fibrillation threshold of rats.ELISA kits were used to detect the contents of CK-MB and cTnT in the serum of rats.TUNEL immunofluorescence was used to detect the apoptosis of cells in the myocardial tissue of rats.Results Compared with the Control group,the LVEF and LVFS of rats in the DOX group were significantly reduced(P<0.01).The results of intracardiac electrophysiology suggested that compared with the Control group,the heart rate(HR),QTc interval,P wave amplitude,R wave amplitude,QRS duration,QT interval,and ST segment amplitude of rats in the DOX group all changed significantly(P<0.05),while there was no statistical significance in PR interval,Q wave amplitude,S wave amplitude,and T wave amplitude.On the electrocardiogram,the P wave disappeared and f waves with unequal spacing and different sizes appeared,and the RR intervals were inconsistent.Ventricular fibrillation was induced by cardiac electrical stimulation.Compared with the Control group,the ventricular fibrillation threshold of rats in the DOX group was significantly reduced(P<0.01).Ventricular fibrillation was induced in the Control group at 20 V,while ventricular fibrillation could be induced in the DOX group at 5 V.The results of ELISA detection showed that compared with the Control group,the contents of CK-MB and cTnT in the DOX group were significantly increased(P<0.05).The results of HE staining and TUNEL staining showed that compared with the Control group,the myocardial tissue structure of rats in the DOX group was disordered,and myocardial cell apoptosis was significantly increased(P<0.05).Conclusion DOX-induced acute cardiotoxicity in rats results in decreased cardiac function,aggravated myocardial injury,increased susceptibility to ventricular arrhythmias,and decreased ventricular fibrillation threshold.