Assessment of Subclinical Doxorubicin-induced Cardiotoxicity in a Rat Model by Speckle-Tracking Imaging

Abstract

BackgroundsDespite their clear therapeutic benefits, anthracycline-induced cardiotoxicity is a major concern limiting the ability to reduce morbidity and mortality associated with cancers. The early identification of anthracycline-induced cardiotoxicity is of vital importance to assess the cardiac risk against the potential cancer treatment.ObjectiveTo investigate whether speckle-tracking analysis can provide a sensitive and accurate measurement when detecting doxorubicin-induced left ventricular injury.MethodsWistar rats were divided into 4 groups with 8 rats each, given doxorubicin intraperitoneally at weekly intervals for up to 4 weeks. Group 1: 2.5 mg/kg/week; group 2: 3 mg/kg/week; group 3: 3.5mg/kg/week; group 4: 4mg/kg/week. An additional 5 rats were used as controls. Echocardiographic images were obtained at baseline and 1 week after the last dose of treatment. Radial (Srad) and circumferential (Scirc) strains, radial (SRrad) and circumferential (SRcirc) strain rates were analyzed. After the experiment, cardiac troponin I (cTnI) was analyzed and the heart samples were histologically evaluated.ResultsAfter doxorubicin exposure, LVEF was significantly reduced in group 4 (p = 0.006), but remained stable in the other groups. However, after treatment, Srads were reduced in groups 2, 3 and 4 (p all < 0.05). The decrease in Srads was correlated with cTnI (rho = -0.736, p = 0.000) and cardiomyopathy scores (rho = -0.797, p = 0.000).ConclusionRadial strain could provide a sensitive and noninvasive index in early detection of doxorubicin-induced myocardial injury. The changes in radial strain had a significant correlation with myocardial lesions and serum cardiac troponin I levels, indicating that this parameter could accurately evaluate cardiotoxicity severity.

Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician

“…Other short-term models use 2-3.4 mg/kg of DOX every other day, six times intraperitoneally (the total dose is 12-20 mg/kg) (Zbinden et al, 1978;Lanza et al, 1989;Carvalho et al, 2010;Razmaraii et al, 2016;Cappetta et al, 2018;Aygun and Gul, 2019;Barış et al, 2019). Long-term rat models typically use 1-5 mg/kg every week for 2-12 weeks with a cumulative dose of 3-25 mg/kg (Villani et al, 1991;Sacco et al, 2001;Sayed-Ahmed et al, 2001;Rahimi Balaei et al, 2010;Hydock et al, 2012;Hole et al, 2013;Toblli et al, 2014;Kang et al, 2017;Medeiros-Lima et al, 2019;Wang et al, 2019;Chakouri et al, 2020;Sharma et al, 2020). Thus, a short-term high-dose injection model would be suitable for assessing acute cardiotoxicity, while a long-term low-dose model would be suitable for assessing chronic cardiotoxicity.…”

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“…This range was selected according to the cardiotoxic doses used in previous studies. In Kang et al, they have used 10, 12, 14 and 16 mg/kg of cumulative dose of doxorubicin 31 . According to the results of that study, systolic functions were significantly reduced in the rat group that received 16 mg/kg doxorubicin compared to the control.…”

Experimental Research on the Evaluation of Left Ventricular Function by Layered Speckle Tracking in a Constrictive Pericarditis Rat Model

“…[6][7][8] A strain analysis based on STI can be used to evaluate myocardial injury in various heart diseases in experimental rats. [9][10][11][12] Reports have confirmed its usefulness as a simple and accurate method of generating detailed local images of cardiac function. Since Torrent-Guasp 13 first proposed the theory of a continuous helical band of ventricular myocardial fibers in 1957, our understanding of the nature of myocardial motion has been continuously improved.…”

“…Currently, 2‐dimensional speckle‐tracking imaging (STI), based on frame‐by‐frame tracking of myocardial motion, is a relatively new method of angle‐independent quantification of left ventricular function . A strain analysis based on STI can be used to evaluate myocardial injury in various heart diseases in experimental rats . Reports have confirmed its usefulness as a simple and accurate method of generating detailed local images of cardiac function.…”