Early Assessment Of 5-fluorouracil And Bevacizumab Induced Cardiotoxicity By Multimodal Imaging Techniques

Objective:Use the Balb/c mice to establish the chemotherapy induced cardiotoxicity model by injected with bevacizumab and 5-fluorouracil,and observe the myocardial injury by speckle tracking echocardiography and various detection techniques and methods to assist the assessment of cardiac injury,so as to find the monitoring means for the early assessment of myocardial toxicity of antitumor drugs.Methods:The healthy male Balb/c mice were randomly divided into two groups:control group and 5-fluorouracil+bevacizumab group.The 5-fluorouracil+bevacizumab group were given intraperitoneal injection of bevacizumab 5mg/kg and 5-fluorouracil 30mg/kg,once every two days,for 14 days.The body weight and nutritional status of the mice were monitored.Echocardiography was performed before injection and on the 4th day,the 7th day,the 14th day after injection.These parameters were used for statistical analysis:the thickness of interventricular septum and left ventricular posterior wall,the left ventricular interior diameter of diastole and systole,left ventricular ejection fraction and fractional shortening.Meanwhile,the longitudinal strain,radial strain,circumferential strain,longitudinal strain rate,radial strain rate and circumferential strain rate of the left ventricle were monitored by speckle tracking echocardiography.PET-CT was used to perform ¹⁸F-FDG myocardial imaging to detect the uptake of nuclides in all segments of left ventricle.At the same time,routine electrocardiograms of each group of mice were collected to record and analyze the changes of heart rate,heart rhythm and electrocardiographic waveform.And the content of B-type natriuretic peptide in the blood serum of mice was detected.Results:Compared with the control group,on the 7th day after injection of anti-tumor drugs,the long axis global longitudinal strain of the left ventricle in the 5-fluorouracil+bevacizumab group decreased significantly.On the 14th day,the long axis global radial strain and the short axis global circumferential strain decreased compared with the control group.While the long axis longitudinal strain rate,the short axis radial strain rate and the short axis circumferential strain rate slightly decreased,but there was no statistical difference.Compared with the control group,the left ventricular apical segment decreased in the long axis longitudinal strain on the 7th day.The short axis radial strain also decreased on the 7th and 14th day,among which the left ventricular anterior wall and lateral wall strain were statistically different from the control group.The short axis circumferential strain decreased as early as the 7th day,appeared in the left ventricular anterior wall.However,the thickness of left ventricular posterior wall and interventricular septum,left ventricular ejection fraction and fractional shortening were lower than those of the control group on the 14th day after injection.PET-CT showed that in the 5-fluorouracil+bevacizumab group,the uptake of radionuclides in the left ventricle increased on the 7th day and decreased on the 14th day,especially in the left ventricle inferior wall,posterior wall and posterior septum wall.Electrocardiogram showed that the ST deviation increased on the 7th and 14th day after the injection,and the PR interval was longer on the 7th and 14th day after injection than that of the control group.But there was no significant difference in other electrocardiogram indexes.The content of B-type natriuretic peptide in serum did not change significantly on the 7th and 14th day after administration of antitumor drugs.Conclusions:1.Compared with other cardiac detection techniques,speckle tracking echocardiography and ¹⁸F-FDG myocardial imaging can detect myocardial injury in the early stage.2.Global longitudinal strain is the best indicator of cardiotoxicity in speckle tracking echocardiography;3.The decrease of longitudinal strain of left ventricular long axis firstly occurs in the apical segment of left ventricle.The decrease of radial strain of left ventricular long axis firstly occurs in the posterior segment of left ventricle.The decrease of left ventricular short axis radial strain and circumferential strain firstly occurred in the anterior wall of left ventricle.