Guazzi Marco, Samaja Michele, Arena Ross, Vicenzi Marco, Guazzi Maurizio D
Cardiopulmonary Unit, Cardiology Division, University of Milan, San Paolo Hospital, Milan, Italy.
J Am Coll Cardiol. 2007 Nov 27;50(22):2136-44. doi: 10.1016/j.jacc.2007.07.078. Epub 2007 Nov 13.
This study sought to test the functional exercise capacity and endothelial function in a cohort of chronic heart failure (CHF) patients treated with chronic type 5 phosphodiesterase (PDE5) inhibitor.
In CHF, endothelial dysfunction is involved in muscle underperfusion, ergoreflex oversignaling, and exercise ventilation inefficiency. Inhibition of PDE5 by improving endothelial dysfunction might be beneficial.
Stable CHF patients were randomly assigned to placebo (23 patients) or sildenafil at the dose of 50 mg twice per day (23 patients) in addition to their current drug treatment for 6 months, with assessments (at 3 and 6 months) of endothelial function by brachial artery flow-mediated dilatation (FMD), cardiopulmonary exercise testing, and ergoreflex response.
In the sildenafil group only, at 3 and 6 months we observed reduction of systolic pulmonary artery pressure (from 33.7 to 25.2 mm Hg and 23.9 mm Hg), ergoreflex effect on ventilation (from 6.9 to 2.3 l x min(-1) and 1.9 l x min(-1)), ventilation to CO2 production slope (V(E)/VCO2, from 35.5 to 32.1 and 29.8), and breathlessness (score) (from 23.6 to 16.6 and 17.2), and an increase of FMD (from 8.5% to 13.4% and 14.2%), peak VO2 (from 14.8 to 18.5 ml x min(-1) x kg(-1) and 18.7 ml x min(-1) x kg(-1)), and ratio of VO2 to work rate changes (from 7.7 to 9.3 and 10.1). All changes were significant at p < 0.01. In the sildenafil group, a significant correlation was found at 3 and 6 months between changes in FMD and those in ergoreflex. Changes in ergoreflex correlated with those in peak VO2 and V(E)/VCO2 slope. No adverse effects were noted except for flushing in 3 patients.
In CHF, improvement in exercise ventilation and aerobic efficiency with sildenafil is sustained and is significantly related with an endothelium-mediated attenuation of exercising muscle oversignaling. Chronic sildenafil seems to be a remedy based on CHF pathophysiology and devoid of remarkable adverse effects.
本研究旨在测试一组接受慢性5型磷酸二酯酶（PDE5）抑制剂治疗的慢性心力衰竭（CHF）患者的功能运动能力和内皮功能。
在CHF中，内皮功能障碍与肌肉灌注不足、运动反射过度信号传导和运动通气效率低下有关。通过改善内皮功能障碍来抑制PDE5可能有益。
稳定的CHF患者在接受当前药物治疗的基础上，被随机分配至安慰剂组（23例患者）或西地那非组（23例患者），西地那非剂量为每日两次，每次50 mg，为期6个月，并在3个月和6个月时通过肱动脉血流介导的扩张（FMD）、心肺运动测试和运动反射反应评估内皮功能。
仅在西地那非组中，在3个月和6个月时，我们观察到收缩期肺动脉压降低（从33.7降至25.2 mmHg和23.9 mmHg）、运动反射对通气的影响（从6.9降至2.3 l·min⁻¹和1.9 l·min⁻¹）、通气与二氧化碳产生斜率（V(E)/VCO2，从35.5降至32.1和29.8）以及呼吸困难（评分）（从23.6降至16.6和17.2），同时FMD增加（从8.5%增至13.4%和14.2%）、峰值VO2增加（从14.8增至18.5 ml·min⁻¹·kg⁻¹和18.7 ml·min⁻¹·kg⁻¹）以及VO2与工作率变化的比值增加（从7.7增至9.3和10.1）。所有变化在p<0.01时均具有显著性。在西地那非组中，在3个月和6个月时发现FMD变化与运动反射变化之间存在显著相关性。运动反射变化与峰值VO2和V(E)/VCO2斜率变化相关。除3例患者出现潮红外，未观察到不良反应。
在CHF中，西地那非可持续改善运动通气和有氧效率，且与运动肌肉过度信号传导的内皮介导性减弱显著相关。慢性西地那非似乎是一种基于CHF病理生理学且无明显不良反应的治疗方法。
