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March 12, 2005AJP Heart and Circulatory Physiology

Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply

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Population

Langendorff model of the perfused rat heart

Design

Preclinical

Follow-up

1 hour

Authors

MTMałgorzata Tokarska-SchlattnerMZMichael ZauggRSRafaela da Silva

Discussion

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Overview

Early AMPK reduction may precede doxorubicin cardiotoxicity; hypothesis-generating for metabolic-targeted prevention, pending clinical validation.

Structured PICO

P
Population
Langendorff model of the perfused rat heart
I
Intervention
1-h perfusion with 2 or 20 microM doxorubicin (DXR)
O
Outcome
Effects on creatine kinase (CK) and AMP-activated protein kinase (AMPK), functional responses of the perfused heart, structural integrity of the contractile apparatus, and drug accumulation in cardiomyocytessurrogate

Acute doxorubicin cardiotoxicity involves early impairment of cardiac energy metabolism kinases, specifically AMPK and CK, preceding substantial cardiac dysfunction.

Cite This Study

Tokarska-Schlattner et al. (2005) studied this question.

synapsesocial.com/papers/6a6f9c0f75498292b708fcdehttps://doi.org/10.1152/ajpheart.01057.2004
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Early effects of doxorubicin in perfused heart: transcriptional profiling reveals inhibition of cellular stress response genes2010 · 46 citations
  2. 2Absence of Acute Doxorubicin-Induced Dysfunction of Heart Mitochondrial Oxidative Phosphorylation and Creatine Kinase Activities1988 · 11 citations
  3. 3Inhibition of AMPK signalling by doxorubicin: at the crossroads of the cardiac responses to energetic, oxidative, and genotoxic stress2012 · 119 citations
  4. 4Effects of chronic administration of doxorubicin on myocardial creatine phosphokinase and antioxidant defenses and levels of lipid peroxidation in tissues and plasma of rats1989 · 15 citations
  5. 5Creatine Kinase-Overexpression Improves Myocardial Energetics, Contractile Dysfunction and Survival in Murine Doxorubicin Cardiotoxicity2013 · 54 citations