Figure 1 5-fluorouracil and bevacizumab reduced heart weight and increased ST offset and PR interval. (n=8) A: Electrocardiogram showed small differences between control group and 5-fluorouracil + bevacizumab group. B: 5-fluorouracil + bevacizumab caused a small reduction in average heart rate. C: Q wave amplitude reduced on the 14th day after injection. D: No obvious changes in T wave amplitude were seen. E: No obvious changes in QRS interval were seen. F: ST offset increased in 5-fluorouracil + bevacizumab group on the 7th and 14th day after injection. G: PR interval increased in 5-fluorouracil + bevacizumab group on the 7th and 14th day after injection. H: No obvious changes in QT interval were seen. I: the body weight slightly reduced on the 7th and 14th day after injection. J: the heart weight index obviously reduced on the 7th and 14th day after injection. 5-FU + BEV group: 5-fluorouracil + bevacizumab group.
The myocardial uptake increased on the 7th day and decreased on the 14th day on PET-CT : In clinic, 18F-FDG was used to detect myocardial metabolism and survival. Therefore, PET-CT was performed to the mice in each group on the 7th and 14th day after injection. On the 7th day after injection, the myocardial uptake of 5-fluorouracil + bevacizumab group was significantly higher than that of the control group, and the cardiac uptake was diffusely increased, but the corresponding CT scan showed no significant changes in cardiac structure. On the 14th day after injection, the 18F-FDG myocardial uptake in the 5-fluorouracil + bevacizumab group was lower than that in the control group, and lower than that on the 7th day, even some of the ventricular walls were filling defect. And the defect walls were mainly the left ventricle inferior wall、posterior wall and posterior interval. At the same time, the corresponding CT scan showed no significant changes in the heart structure between the two groups. It can be seen that PET can detect cardiotoxicity caused by antineoplastic drugs in the early stage, and the increase of myocardial metabolism in the chemotherapy induced cardiotoxicity may be one of the early manifestations. As figure 3, part A.
No obvious changes in B-type natriuretic peptide concentration were seen: BNP (B-type natriuretic peptide) was a natural hormone with biological activity synthesized by cardiomyocytes, which was mainly expressed in ventricles and also existed in brain tissue. As a quantitative marker of heart failure, BNP not only reflects left ventricular systolic dysfunction, which also reflects left ventricular diastolic dysfunction, valve dysfunction and right ventricular dysfunction. Therefore, we measured the BNP content in serum of mice in each group. Compared with the control group, BNP in the serum of 5-fluorouracil + bevacizumab group on the 7th and 14th day did not change significantly (P >0.05), even in the serum of 5-fluorouracil + bevacizumab group on the 14th day was slightly lower than that on the 7th day. As figure 3, part B.
Revealed myofibril irregular on the 14th day: After 7 and 14 days of injection of 5-fluorouracil and bevacizumab, the hearts of mice were washed and weighed. After HE staining of myocardial sections, it was observed that some of the myofibril arranged irregularly in a small range after 5-fluorouracil and bevacizumab were given. As figure 3, part C.