TY - JOUR
T1 - Sildenafil treatment attenuates ventricular remodeling in an experimental model of aortic regurgitation
AU - Eskesen, Kristian
AU - Olsen, Niels Thue
AU - Dimaano, Veronica L.
AU - Fritz-Hansen, Thomas
AU - Sogaard, Peter
AU - Chakir, Khalid
AU - Steenbergen, Charles
AU - Kass, David
AU - Abraham, Theodore P.
N1 - Publisher Copyright:
© 2015, Eskesen et al.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background: Currently there is no reliable medical treatment for aortic regurgitation (AR). Methods: Thirty-nine Sprague–Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100 mg/kg/day) for a total of 10 weeks. Treatment–effects were measured by serial echocardiography, invasive hemodynamic measurements, and tissue analysis. Results: Rats assigned to early treatment developed less remodeling than untreated rats. Thus, left ventricular (LV) dilation was blunted by sildenafil with end–systolic diameter being significantly smaller (6.6 ± 0.4 vs. 7.7 ± 0.4 mm, respectively, p < 0.05). Also, LV wall thickness was significantly decreased in treated rats compared to controls (2.23 ± 0.08 vs. 2.16 ± 0.05 mm, p < 0.01). Fractional shortening was improved by treatment (p < 0.05). Myocardial fibrosis was borderline decreased by treatment (p = 0.09). Akt was increased in treated compared to controls (p < 0.05). Conclusion: Sildenafil slightly inhibits LV remodeling and improves fractional shortening in rats with AR when treatment is initiated early.
AB - Background: Currently there is no reliable medical treatment for aortic regurgitation (AR). Methods: Thirty-nine Sprague–Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100 mg/kg/day) for a total of 10 weeks. Treatment–effects were measured by serial echocardiography, invasive hemodynamic measurements, and tissue analysis. Results: Rats assigned to early treatment developed less remodeling than untreated rats. Thus, left ventricular (LV) dilation was blunted by sildenafil with end–systolic diameter being significantly smaller (6.6 ± 0.4 vs. 7.7 ± 0.4 mm, respectively, p < 0.05). Also, LV wall thickness was significantly decreased in treated rats compared to controls (2.23 ± 0.08 vs. 2.16 ± 0.05 mm, p < 0.01). Fractional shortening was improved by treatment (p < 0.05). Myocardial fibrosis was borderline decreased by treatment (p = 0.09). Akt was increased in treated compared to controls (p < 0.05). Conclusion: Sildenafil slightly inhibits LV remodeling and improves fractional shortening in rats with AR when treatment is initiated early.
KW - Animal models
KW - Aortic regurgitation
KW - Echocardiography
KW - Phosphodiesterase
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U2 - 10.1186/s40064-015-1317-8
DO - 10.1186/s40064-015-1317-8
M3 - Article
AN - SCOPUS:84944047634
SN - 2193-1801
VL - 4
JO - SpringerPlus
JF - SpringerPlus
IS - 1
M1 - 592
ER -