西地那非治疗可减轻主动脉瓣反流实验模型中的心室重构。

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

作者信息

Eskesen Kristian, Olsen Niels Thue, Dimaano Veronica L, Fritz-Hansen Thomas, Sogaard Peter, Chakir Khalid, Steenbergen Charles, Kass David, Abraham Theodore P

机构信息

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

Johns Hopkins Medical Institutions, Division of Cardiology, Baltimore, MD USA.

出版信息

Springerplus. 2015 Oct 13;4:592. doi: 10.1186/s40064-015-1317-8. eCollection 2015.

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.

背景

目前对于主动脉瓣反流（AR）尚无可靠的药物治疗方法。

方法

39只Sprague-Dawley大鼠接受了AR造模或假手术。将接受治疗的大鼠分为早期或晚期给予西地那非治疗组（100毫克/千克/天），共治疗10周。通过连续超声心动图、有创血流动力学测量和组织分析来评估治疗效果。

结果

早期接受治疗的大鼠与未治疗的大鼠相比，心脏重塑程度较轻。因此，西地那非可减轻左心室（LV）扩张，使收缩末期直径显著减小（分别为6.6±0.4毫米和7.7±0.4毫米，p<0.05）。此外，与对照组相比，治疗组大鼠的LV壁厚度显著降低（2.23±0.08毫米对2.16±0.05毫米，p<0.01）。治疗可改善缩短分数（p<0.05）。治疗使心肌纤维化程度略有降低（p=0.09）。与对照组相比，治疗组的Akt增加（p<0.05）。