Cardiovascular Toxicology

, Volume 13, Issue 3, pp 244-253

First online:

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

  • David P. SontagAffiliated withDepartment of Physiology, University of Manitoba
  • , Jie WangAffiliated withDepartment of Physiology, University of Manitoba
  • , Elissavet KardamiAffiliated withDepartment of Human Anatomy and Cell Science, University of ManitobaInstitute of Cardiovascular Science, St. Boniface Hospital Research Centre
  • , Peter A. CattiniAffiliated withDepartment of Physiology, University of Manitoba Email author 

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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.


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