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Updated: Oct 24, 2025

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Repeated Remote Ischemic Conditioning Reduces Doxorubicin-Induced Cardiotoxicity.

Quan He1, Fangfei Wang1, Thomas D Ryan1

  • 1The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

JACC. Cardiooncology
|August 16, 2021
PubMed
Summary

Repeated remote ischemic preconditioning (rRIC) protected mice against doxorubicin-induced heart damage. This novel approach also shielded other organs, offering a potential strategy to mitigate chemotherapy side effects.

Keywords:
BUN, blood urea nitrogenapoptosisautophagycardiac functiondoxorubicininflammationmultiorgan toxicityrRIC, repeated remote ischemic conditioningrepeated remote ischemic conditioning

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Area of Science:

  • Cardiovascular Biology
  • Oncology
  • Nephrology
  • Hepatology

Background:

  • Doxorubicin chemotherapy causes dose-limiting cardiotoxicity, impacting treatment efficacy.
  • Remote ischemic conditioning (RIC) shows cardioprotective potential in various cardiovascular injury models.
  • The efficacy of repeated remote ischemic preconditioning (rRIC) against doxorubicin cardiotoxicity remains under investigation.

Purpose of the Study:

  • To investigate the cardioprotective effects of rRIC in a mouse model of doxorubicin-induced cardiotoxicity.
  • To evaluate the impact of rRIC on cardiac function and myocardial biology following doxorubicin administration.
  • To assess the potential of rRIC for multiorgan protection against doxorubicin toxicity.

Main Methods:

  • Mice underwent rRIC before and after doxorubicin treatment.
  • Cardiac function was evaluated using echocardiography.
  • Myocardial tissue was analyzed using molecular techniques to assess cellular damage, inflammation, and autophagy.

Main Results:

  • Doxorubicin induced significant cardiotoxicity, evidenced by reduced cardiac function, myocyte damage, and increased fibrosis.
  • rRIC significantly abrogated doxorubicin-induced cardiotoxicity, improving left ventricular ejection fraction (47.5% vs. 51.6%, p=0.017).
  • rRIC demonstrated multiorgan protective effects and attenuated cardiomyocyte apoptosis, inflammation, and enhanced autophagy in the myocardium.

Conclusions:

  • rRIC effectively mitigates doxorubicin-induced cardiotoxicity in mice.
  • rRIC offers potential for protecting multiple organs from chemotherapy-related damage.
  • rRIC represents a promising strategy to improve the safety profile of doxorubicin chemotherapy.