EFFECTS OF DIGITOXIN ON MYOCARDIAL COLLAGEN DEPOSITION IN AN EXPERIMENTAL FIBROSIS MODEL

Abstract

Background Recent studies showed that digital compounds may regulate the interstitial collagen deposition. The objective of our study was to evaluate the role of the digital on myocardial fibrosis in an experimental model. Methods The sample was divided in 20 rats from the control group (CG); 20 rats submitted to an experimental model of fibrosis, in which the rats were uninefrectomized, drank water with 1% NaCl during the protocol and received aldosterone through an osmotic minipump (AG); and 20 rats submitted to the same experimental model were treated with digitoxin in a daily dose of 100 g/Kg (DAG). All animals were submitted to high resolution echocardiography at the beginning and the end of the study. Serum B-type natriuretic peptide (BNP) levels were measured by Elisa. After 6 weeks of treatment the animals were euthanized, Picrosirius Red stain was used to quantify myocardial collagen, and gelatin zymography was performed for metalloproteinases-2 and metalloproteinases-9 activity of the heart samples. Results The AG (1.4 ± 0.14 g) and DAG (1.25 ± 0.1 g) showed increased left ventricular mass compared to CG (1.13 ± 0.08 g; p=0.001) and relative wall thickness (AG: 0.68 ± 0.15 and DAG: 0.75 ± 0.22 vs CG: 0.47± 0.07; p=0.001) reflecting concentric hypertrophy by high resolution echocardiogram. The myocardial performance index showed a increased in AG (0.49 ± 0.08) compared to DAG (0.40 ± 0.13) and CG (0.32 ± 0.06; p=0.001), reflecting global myocardial dysfunction. The right and left ventricular interstitial and the perivascular collagen volume fraction showed a significant increase of AG compared to DAG and CG (p< 0.001). The BNP levels were increased in AG (1.07 ± 0.32 ng/ml) compared to DAG (0.84 ± 0.21 ng/ml) and CG (0.75 ± 0.19 ng/ml; p=0.01). The metalloproteinases levels did not differ among the groups. There was a positive correlation between fractional shortening and BNP levels of the GAD animals (r= 0.95; p= 0.0001). Conclusions These data demonstrate the digitoxin positive effect on the myocardial collagen deposition in this experimental model of interstitial fibrosis and could have a new therapeutic target previously unexplored. ACC Moderated Poster Contributions McCormick Place South, Hall A Monday, March 26, 2012, 11:00 a.m.-Noon Session Title: Alterations in Cardiac Morphology and Function Abstract Category: 15. Heart Failure: Basic Presentation Number: 1231-553