Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy A Randomized, Controlled Clinical Trial Using Magnetic Resonance Imaging With Myocardial Tagging
Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy A Randomized, Controlled Clinical Trial Using Magnetic Resonance Imaging With Myocardial Tagging
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DOI：
10.1161/circulationaha.111.063412
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发表时间：
2012-05-15
期刊：
影响因子：
37.8
通讯作者：
Lenzi, Andrea
中科院分区：
文献类型：
--
作者：
Giannetta, Elisa;Isidori, Andrea M.;Lenzi, Andrea
背景：cgmp磷酸二酯酶5型蛋白在心肌肥大中表达上调。然而，尚未确定5型磷酸二酯酶抑制是否在人类非缺血性心脏病中发挥抗重构作用。我们在糖尿病心肌病模型中探索了选择性磷酸二酯酶5型抑制剂西地那非的心脏修复特性。方法与结果：59例心脏磁共振成像符合非缺血性、非衰竭糖尿病性心肌病（环向应变[sigma]减小，-12.6 +/- 3.1%；左室[LV]扭转[θ]增大，18.4 +/- 4.6度；左室质量体积比增大，2.1 +/- 0.5 g/mL）的糖尿病男性（60.3 +/- 7.4岁）随机分为西地那非组和安慰剂组（100 mg/d）。基线时，代谢指标与扭转、应变、n端前b型利钠肽、血管内皮生长因子、单核细胞趋化蛋白-1和血压相关。3个月后，与安慰剂相比，西地那非在左室扭转方面产生了显著改善(δ θ：西地那非，-3.89 +/- 3.11度与安慰剂相比，2.13 +/- 2.35度
Background-cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy.Method and Results-Fifty-nine diabetic men (60.3 +/- 7.4 years) with cardiac magnetic resonance imaging consistent with nonischemic, nonfailing diabetic cardiomyopathy (reduced circumferential strain [sigma], -12.6 +/- 3.1%; increased left ventricular [LV] torsion [theta], 18.4 +/- 4.6 degrees; and increased ratio of LV mass to volume, 2.1 +/- 0.5 g/mL) were randomized to receive sildenafil or placebo (100 mg/d). At baseline, the metabolic indices were correlated with torsion, strain, N-terminal pro-B-type natriuretic peptide, vascular endothelial growth factor, monocyte chemotactic protein-1, and blood pressure. After 3 months, sildenafil produced a significant improvement compared with placebo in LV torsion (Delta theta: sildenafil, -3.89 +/- 3.11 degrees versus placebo, 2.13 +/- 2.35 degrees; P