Cardiovascular complications of chemotherapy: A synopsis

Steingo, L

doi:10.24170/9-4-1831

Cited by 1 publication

(1 citation statement)

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“…CP is an anti-cancer drug that is used in the treatment of rheumatoid arthritis, lupus erythematosus, multiple sclerosis, neuroblastoma, and other types of cancer and it is also used in transplantology 25 . Unfortunately, its action is often associated with cardiovascular side effects such as atrioventricular block, tachyarrhythmias, heart failure, and myocarditis when taken in high doses (i.e., 100-200 mg/kg) [1][2][3][4][5][6] . While heart failure and myocarditis are caused by metabolites of CP 8 , atrioventricular block and tachyarrhythmias might be associated with the mechanisms of arrhythmia occurrence under CP influence on a cellular level, particularly when small doses of the drug are taken (i.e., less than 100 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

Cyclophosphamide arrhythmogenicitytesting using human-induced pluripotent stem cell-derived cardiomyocytes

Podgurskaya

Slotvitsky

Tsvelaya

et al. 2021

Sci Rep

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Cyclophosphamide (CP) is an anticancer drug, an alkylating agent. Cardiotoxicity of CP is associated with one of its metabolites, acrolein, and clinical cardiotoxicity manifestations are described for cases of taking CP in high doses. Nevertheless, modern arrhythmogenicity prediction assays in vitro include evaluation of beat rhythm and rate as well as suppression of cardiac late markers after acute exposure to CP, but not its metabolites. The mechanism of CP side effects when taken at low doses (i.e., < 100 mg/kg), especially at the cellular level, remains unclear. In this study conduction properties and cytoskeleton structure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) obtained from a healthy donor under CP were evaluated. Arrhythmogenicity testing including characterization of 3 values: conduction velocity, maximum capture rate (MCR) measurements and number of occasions of re-entry on a standard linear obstacle was conducted and revealed MCR decrease of 25% ± 7% under CP. Also, conductivity area reduced by 34 ± 15%. No effect of CP on voltage-gated ion channels was found. Conduction changes (MCR and conductivity area decrease) are caused by exposure time-dependent alpha-actinin disruption detected both in hiPSC-CMs and neonatal ventricular cardiomyocytes in vitro. Deviation from the external stimulus frequency and appearance of non-conductive areas in cardiac tissue under CP is potentially arrhythmogenic and could develop arrhythmic effects in vivo.

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