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Doxorubicin induces early left ventricular dysfunction and metalloproteinase activation in rats
Author(s) -
Polegato Bertha Furlan,
Azevedo Paula Schmidt,
Minicucci Marcos Ferreira,
Chiuso-Minicucci Fernanda,
Castan Eduardo,
Carvalho Robson Francisco,
Matsubara Beatriz Bojikian,
Matsubara Luiz Shiguero
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1036.10
Subject(s) - isovolumetric contraction , medicine , doxorubicin , cardiotoxicity , pathophysiology , endocrinology , diastole , ryanodine receptor , cardiac function curve , cardiology , heart failure , receptor , chemotherapy , blood pressure
Pathophysiological mechanism of the acute doxorubicin‐induced cardiotoxicity is not fully understood. The purpose of this study was to evaluate alterations in cardiac structure and function 48 hours after doxorubicin infusion in rats. Thus, male Wistar rats (n = 35) received an intraperitonealy single‐dose of doxorubicin (20 mg / kg) or saline (control group). Morphological, functional and biochemical analysis were performed. Echocardiographic analysis showed increased in isovolumetric relaxation time (20.3 ± 4.3 ms vs 24.7 ± 4.2 ms; p=0.007) and decreased left ventricular fractional shortening (0.59 ± 0.07 vs. 0.51± 0.05; p<0.001) in treated rats. This group also presented increased myocardial passive stiffness in isolated perfused heart study (14.7 ± 1.5 % vs 12 ± 2.2 %; p<0,05). There were no changes in TNF‐á, IFN‐ɤ, IL‐1 and ICAM‐1 or gene expression of ryanodine receptor, fosfolamban and Serca‐2a between groups. However, there were activation of MMP 2 (0.11 ± 0.01 vs 0.06 ± 0.02; p=0.002) and MMP 9 (0.07 ± 0.01 vs 0.05 ± 0.01; p=0.009) in the myocardium of the treated rats. In conclusion, doxorubicin caused early systolic and diastolic dysfunction, and this dysfunction is associated with increased MMP 2 and 9 activity.