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Sildenafil treatment attenuates ventricular remodeling in an experimental model of aortic regurgitation.

Eskesen K, Olsen NT, Dimaano VL, Fritz-Hansen T, Sogaard P, Chakir K, Steenbergen C, Kass D, Abraham TP - Springerplus (2015)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Johns Hopkins Medical Institutions, Division of Cardiology, Baltimore, MD USA ; Department of Cardiology, Gentofte Hospital, University of Copenhagen, Niels Andersensvej 65, 2900 Hellerup, Denmark.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Left ventricle remodeling. LV diameters in end-diastole (LVEDD) and end–systole (LVESD) (left panel) and LV wall thickness (right panel) for early treated groups (upper) and late treated groups (lower). Asterisk indicate significant difference between AR vs. AR + SIL and hash indicate difference between sham vs. AR at individual time points (t test/ANOVA). Vertical bar and related p value is for overall difference (repeated measures)
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Fig2: Left ventricle remodeling. LV diameters in end-diastole (LVEDD) and end–systole (LVESD) (left panel) and LV wall thickness (right panel) for early treated groups (upper) and late treated groups (lower). Asterisk indicate significant difference between AR vs. AR + SIL and hash indicate difference between sham vs. AR at individual time points (t test/ANOVA). Vertical bar and related p value is for overall difference (repeated measures)

Mentions: Echocardiography showed AR + SIL (early) rats to develop less remodeling than AR (early). LV dimensions increased in all rats with AR, starting immediately after AR–induction. In AR (early) LV dilation continued throughout the study-period while treatment with sildenafil blunted this response, Fig. 2. LVEDD was significantly lower after six and 9 weeks but did not in overall analysis. LVESD was significantly lower in AR + SIL (early) compared to AR (early) after twelve weeks and in overall analysis (p = 0.03). Furthermore average LV wall thickness was significantly lower in AR + SIL (early) compared to AR (early) in overall analysis (p = 0.004) and consequently a lower LV mass was observed (p = 0.005, not shown).Fig. 2


Sildenafil treatment attenuates ventricular remodeling in an experimental model of aortic regurgitation.

Eskesen K, Olsen NT, Dimaano VL, Fritz-Hansen T, Sogaard P, Chakir K, Steenbergen C, Kass D, Abraham TP - Springerplus (2015)

Left ventricle remodeling. LV diameters in end-diastole (LVEDD) and end–systole (LVESD) (left panel) and LV wall thickness (right panel) for early treated groups (upper) and late treated groups (lower). Asterisk indicate significant difference between AR vs. AR + SIL and hash indicate difference between sham vs. AR at individual time points (t test/ANOVA). Vertical bar and related p value is for overall difference (repeated measures)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4628012&req=5

Fig2: Left ventricle remodeling. LV diameters in end-diastole (LVEDD) and end–systole (LVESD) (left panel) and LV wall thickness (right panel) for early treated groups (upper) and late treated groups (lower). Asterisk indicate significant difference between AR vs. AR + SIL and hash indicate difference between sham vs. AR at individual time points (t test/ANOVA). Vertical bar and related p value is for overall difference (repeated measures)
Mentions: Echocardiography showed AR + SIL (early) rats to develop less remodeling than AR (early). LV dimensions increased in all rats with AR, starting immediately after AR–induction. In AR (early) LV dilation continued throughout the study-period while treatment with sildenafil blunted this response, Fig. 2. LVEDD was significantly lower after six and 9 weeks but did not in overall analysis. LVESD was significantly lower in AR + SIL (early) compared to AR (early) after twelve weeks and in overall analysis (p = 0.03). Furthermore average LV wall thickness was significantly lower in AR + SIL (early) compared to AR (early) in overall analysis (p = 0.004) and consequently a lower LV mass was observed (p = 0.005, not shown).Fig. 2

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Johns Hopkins Medical Institutions, Division of Cardiology, Baltimore, MD USA ; Department of Cardiology, Gentofte Hospital, University of Copenhagen, Niels Andersensvej 65, 2900 Hellerup, Denmark.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus