Multimodal Ultrasound Evaluation Of Ca²⁺ Blocker Intervention In Arsenic-Induced Cardiac Dysfunction In Rats

Objective:（1）To investigate the value of multimodal echocardiography in assessing changes in cardiac function of rats during the early stages of arsenic trioxide（ATO）cardiotoxicity.（2）To observe the effect of Ca²⁺blocker（2-Aminoethoxydiphenyl borate:2-APB）on hearts of rats after intervention treatment in ATO cardiotoxicity model.Methods:Forty SD male rats were randomly divided into five groups:Control group（Control）,2-APB negative control group（2-APB）,natural recovery group after ATO poisoning（ATO）,low-dose 2-APB intervention group after ATO poisoning（2-APB_L）,and high-dose 2-APB intervention group after ATO poisoning（2-APB_H）,8 rats in each group.Firstly,the model of ATO poisoning was made（ATO was injected daily for 10 days）:ATO,2-APB_L and 2-APB_H groups were intraperitoneally injected with 5mg/kg/day of ATO,Control and 2-APB groups with the same quality saline.Then received 2-APB intervention treatment（2-APB was injected every other day for 21 days）:after modeling,2-APB_L and 2-APB_H groups were injected intraperitoneally with 2 and 4mg/kg/day doses of 2-APB,respectively,2-APB group was injected with 4mg/kg/day 2-APB,Control and ATO groups were injected with the same quality saline.At the end of drug administration,rats were given echocardiography to obtain relevant parameters:M-mode parameters（left ventricular fraction shortening:LVFS,left ventricular ejection fraction:LVEF,etc）,speckle-tracked stratified strain（STE）parameters（global longitudinal/circumferential strain in the endocardial/mid-myocardial/epicardial:GLS/GCS-endo/mid/epi,LS and CS for each segment of the endocardial layer）,myocardial contrast echocardiography（MCE）parameters（myocardial perfusion rate:WIS,myocardial blood volume:PI,myocardial perfusion blood flow:WIS×PI,area under the curve:AUC,time to peak:TTP）.After ultrasonography,firstly,rats were executed and blood specimens were collected from rats for subsequent detection of myocardial injury markers（lactate dehydrogenase:LDH,glutamate transaminase:AST,creatine kinase:CK）,key enzymes of oxidative stress（malondialdehyde:MDA,glutathione peroxidase:GSH-px,super oxide dismutase:SOD）and sarcoplasmic reticulum Ca²⁺-ATPase（SERCA）.And heart specimens of rats were obtained for subsequent observation of myocardial histopathological patterns.Results:（1）Basic condition:Heart rate and QTc increased in the ATO group compared with the Control group,and showed reduction after 2-APB intervention treatment.（2）M-type parameters:LVFS and LVEF decreased in the ATO group compared with the Control group,and recovered after 2-APB intervention treatment.（3）STE parameters:the absolute value of GLS/GCS-endo/mid/epi decreased in the ATO group compared with the Control group,and the partial parameters showed different degrees of recovery after different doses of 2-APB intervention treatment.（4）MCE parameters:WIS,PI,WIS×PI and AUC decreased in the ATO group compared with the Control group,and showed different degrees of recovery after different doses of 2-APB intervention treatment.（5）Myocardial histopathological morphology:the hematoxylin-eosin staining and ultrastructural showed that the structure of cardiomyocytes was significantly damaged in the ATO group compared with the Control group,and the damage showed different degrees of reduction after different doses of 2-APB intervention treatment.（6）Myocardial CD31 immunofluorescence:The CD31 absorbance value and the number of blue-stained nuclei increased in the ATO group compared with the Control group,and showed different degrees of recovery after different doses of 2-APB intervention treatment.（7）Myocardial injury markers,oxidative stress key enzymes and SERCA activities:AST,CK,LDH and MDA increased,SOD,GSH-px and SERCA activities decreased in the ATO group compared with the Control group,and showed different degrees of recovery after different doses of 2-APB intervention treatment.Conclusions:（1）Multimodal echocardiography can provide a more comprehensive and accurate assessment of cardiac function in rats during the early stages of ATO cardiotoxicity,and GLS-endo is more sensitive indicator to reflect the changes of myocardial mechanical motion changes in STE parameters.（2）2-APB may mitigate the cardiotoxicity of ATO by resisting excessive oxidative stress and maintaining calcium homeostasis to exert myocardial protective effects.