Children surviving cancer and chemotherapy are at risk for adverse health events including heart failure that may be delayed by years

 

Abstract

Children surviving cancer and chemotherapy are at risk for adverse health events including heart failure that may be delayed by years. Although the early effects of doxorubicin-induced cardiotoxicity may be attributed to a direct effect on the cardiomyocytes, the mechanisms underlying the delayed or late effects (8-20 years) are unknown. The goals of this project were to develop a model of late-onset doxorubicin-induced cardiotoxicity to better delineate the underlying pathophysiology responsible. The underlying hypothesis was that doxorubicin-induced "late-onset cardiotoxicity" was the result of mitochondrial dysfunction leading to cell failure and death. Wistar rats, 3 to 4 weeks of age, were randomly assigned to vehicle or doxorubicin injection groups (1-45 mg/kg). Cardiovascular function was unaltered at the lower dosages (1-15 kg/mg), but beginning at 6 months post injection significant cardiac degradation was observed in the 45 mg/kg group. Doxorubicin significantly increased myocardial mtDNA damage. In contrast, in isolated c-kit+ left ventricular (LV) cells, doxorubicin treatment did not increase mtDNA damage. Biomarkers of senescence within the LV were significantly increased, suggesting accelerated aging of the LV. Doxorubicin also significantly increased LV histamine content suggestive of mast cell activation. Using flow cytometry, a significant expansion of the c-kit+ and SSEA1+ cell populations within the left ventricle were concomitant with significant decreases in the circulating peripheral blood population of these cells. These results are consistent with the concept that doxorubicin induced significant damage to the cardiomyocyte population and that although the heart attempted to compensate it eventually succumb to an inability for self-repair.

PMID: 31913702 [PubMed - as supplied by publisher]

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Fluorouracil-induced Takotsubo cardiomyopathy causing cardiogenic shock: a case report of clinical and acute cardiac magnetic resonance imaging features.

Fluorouracil-induced Takotsubo cardiomyopathy causing cardiogenic shock: a case report of clinical and acute cardiac magnetic resonance imaging features.

Eur Heart J Case Rep. 2019 Dec;3(4):1-6

Authors: Joy G, Eissa H, Al Karoudi R, White SK