The Assessment Of Acute Myocardial Toxicity At Early Stage Induced By Doxorubicin In Rats Using Ultrasonic Layer-specific Strain Imaging

Objective: To evaluate the change of transmural myocardial circumferential strain at three specific layers of the left ventricle at papillary muscle level in short-axis view of SD rats before and after doxorubicin administration using two-dimensional speckle tracking(two-dimensional speckle tracing imaging,2D-STI)based myocardial layer-specific strain ultrasound imaging,and to demonstrate the myocardial mechanical characteristics of doxorubicin-induced acute cardiac toxicity at early stage in rats.Methods : Thirty-two SD male rats weighing 300-350 g were labelled and randomly divided into doxorubicin group(DOX group,n=16)and blank control group(n=16).Doxorubicin hydrochloride at concentration of 2mg/ml was injected intraperitoneally according to the dosage of 12mg/kg at one time in DOX group: The same volume of saline was injected intraperitoneally once in blank control group: The LVEDD,LVESD,IVSd,LVPWd,LVEF,FS were measured and derived using two-dimensional gray-scale echocardiography at left ventricular papillary muscle level in short axis view at three time points before administration,and at 24 hours and 48 hours after administration.The circumferential strains of subendocardium,medium and subepicardium at left ventricular papillary muscle level in short axis view were obtained using2D-STI based myocardial layer-specific strain ultrasound imaging.The values of LVEF,FS and the transmural global myocardial circumferential strain at different layers of the left ventricular wall at papillary muscle level in short axis view at three time points were compared between the two groups for difference.After echocardiographic exam at 48 hrs,the plasma of venous blood from the two groups was sampled respectively,and the blood myocardial enzyme spectrum(i.e.CK、HBDH、LDH)was detected.Before administration,24 hours after administration and 48 hours after administration,three rats in each group were randomly killed after echocardiography.The hearts of the rats were taken for HE staining for myocardial pathological examination.Results:(1)In the two groups,there was a circumferential strain gradient of the left ventricular wall at the papillary muscle level in the short axis of view: subendocardium >medium > epicardial myocardium.(2)In the DOX group,the circumferential strain of the subendocardial myocardium decreased at 48 hours after DOX administration.Compared with before administration,the difference was statistically significant(-25.13±10.6 VS-17.04±2.89,t=2.3,p<0.05).(3)There was no significant difference at the three layers of myocardial circumference strain between the control group and the DOX group(p > 0.05)as while as LVEDD、LVESD、IVS、LVPW、LVEF 、FSat three-time points(p > 0.05).(4)The pathological changes were mainly myocardial cell edema,vascular degeneration,myocardial nucleus atrophy,dissolution,interstitial edema and capillary dilatation in doxorubicin group,obviousely atsubendocardial cardiomyocytes.The results of myocardial enzyme spectrum indicated that the level of CK、HBDH、LDH of DOX group was higher than those of control group,and there was a statistical difference of LDH between them(p < 0.05).Conclusion The early myocardial dysfunction of acute cardiac toxicity in SD rats induced by doxorubicin occured at subendocardium firstly with pathological changes of subendocardial cardiomyocytes at 48 hours after doxorubicin administration.The 2D-STI based myocardial layer-specific strain ultrasonic imaging could be used to detect and evaluate quantitatively the DOX induced acute transmural myocardial deformation damage of left ventricular wall in SD rats at early stage.