Cardiovascular Toxicology

, Volume 13, Issue 3, pp 244–253

FGF-2 and FGF-16 Protect Isolated Perfused Mouse Hearts from Acute Doxorubicin-Induced Contractile Dysfunction

  • David P. Sontag
  • Jie Wang
  • Elissavet Kardami
  • Peter A. Cattini
Article

Abstract

The anti-cancer drug doxorubicin is associated with an increased risk of cardiac damage and dysfunction, which can be acute as well as chronic. Fibroblast growth factor 2 (FGF-2) provides cardioprotection from ischemia–reperfusion injury but its effects on doxorubicin-induced damage are not known. We investigated the acute effects of doxorubicin administered in the absence and presence of FGF-2 pre-treatment, on isolated mouse perfused heart function over a period of 120 min. Doxorubicin elicited a significant decrease in left ventricular developed pressure (DP) at 30 min that persisted throughout the study. No effect on lactate dehydrogenase levels was detected in the perfusate, suggesting a lack of significant plasma membrane damage. FGF-2 pre-treatment lessened the deleterious effect of doxorubicin on DP significantly, and this beneficial effect of FGF-2 was blunted by protein kinase C inhibition with chelerythrine. Pre-treatment with a non-mitogenic FGF-2 mutant or FGF-16 also protected against a doxorubicin-induced decrease in DP. FGF-16 as well as FGF-2 pre-treatment elicited a small and transient negative inotropic effect. In conclusion, FGF-2 and FGF-16 increase resistance to acute doxorubicin-induced cardiac dysfunction, and protein kinase C activation is implicated in this response.

Keywords

Doxorubicin Cardioprotection Mouse Langendorff preparation Developed pressure FGF-2 FGF-16 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • David P. Sontag
    • 1
  • Jie Wang
    • 1
  • Elissavet Kardami
    • 2
    • 3
  • Peter A. Cattini
    • 1
  1. 1.Department of PhysiologyUniversity of ManitobaWinnipegCanada
  2. 2.Department of Human Anatomy and Cell ScienceUniversity of ManitobaWinnipegCanada
  3. 3.Institute of Cardiovascular ScienceSt. Boniface Hospital Research CentreWinnipegCanada

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