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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

Protein analysis. Bars indicate the ratio of phosphorylated (P) to total (T) protein or housekeeping protein (GAPDH) normalized to untreated (AR). *p < 0.05 untreated (AR) vs. treated (AR + SIL)
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Fig5: Protein analysis. Bars indicate the ratio of phosphorylated (P) to total (T) protein or housekeeping protein (GAPDH) normalized to untreated (AR). *p < 0.05 untreated (AR) vs. treated (AR + SIL)

Mentions: We did not find any difference in phosphorylated levels of Akt S473 and Akt S308 between controls and sham–operated rats, while we found an increase in phosphorylated Akt S473 in AR + SIL compared to AR (p = 0.002). Total calcineurin and phosphorylated ratio of CamKII, ERK, JNK, and p38 were unchanged between groups, Fig. 5.Fig. 5


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)

Protein analysis. Bars indicate the ratio of phosphorylated (P) to total (T) protein or housekeeping protein (GAPDH) normalized to untreated (AR). *p < 0.05 untreated (AR) vs. treated (AR + SIL)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Protein analysis. Bars indicate the ratio of phosphorylated (P) to total (T) protein or housekeeping protein (GAPDH) normalized to untreated (AR). *p < 0.05 untreated (AR) vs. treated (AR + SIL)
Mentions: We did not find any difference in phosphorylated levels of Akt S473 and Akt S308 between controls and sham–operated rats, while we found an increase in phosphorylated Akt S473 in AR + SIL compared to AR (p = 0.002). Total calcineurin and phosphorylated ratio of CamKII, ERK, JNK, and p38 were unchanged between groups, Fig. 5.Fig. 5

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