无机硝酸盐对射血分数保留的心力衰竭患者运动能力的影响。
Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction.
作者信息
Zamani Payman, Rawat Deepa, Shiva-Kumar Prithvi, Geraci Salvatore, Bhuva Rushik, Konda Prasad, Doulias Paschalis-Thomas, Ischiropoulos Harry, Townsend Raymond R, Margulies Kenneth B, Cappola Thomas P, Poole David C, Chirinos Julio A
机构信息
From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia (P.Z., P.S.-K., P.K., K.B.M., T.P.C., J.A.C.); Division of Cardiology, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA (D.R., P.S.-K., S.G., R.B., J.A.C.); Children's Hospital of Philadelphia Research Institute, Philadelphia, PA (P.-T.D., H.I.); Division of Nephrology/Hypertension. Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); and Departments of Kinesiology, Anatomy, and Physiology, Kansas State University, Manhattan (D.C.P.).
出版信息
Circulation. 2015 Jan 27;131(4):371-80; discussion 380. doi: 10.1161/CIRCULATIONAHA.114.012957. Epub 2014 Dec 22.
BACKGROUND
Inorganic nitrate (NO3(-)), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3(-) supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise.
METHODS AND RESULTS
Seventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3-rich beetroot juice (NO3(-), 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak VO2, total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 μmol/L; P=0.0003), peak VO2 (12.6±3.7 versus 11.6±3.1 mL O2·min(-1)·kg(-1); P=0.005), and total work performed (55.6±35.3 versus 49.2±28.9 kJ; P=0.04). However, efficiency was unchanged. NO3(-) led to greater reductions in systemic vascular resistance (-42.4±16.6% versus -31.8±20.3%; P=0.03) and increases in cardiac output (121.2±59.9% versus 88.7±53.3%; P=0.006) with exercise. NO3(-) reduced aortic augmentation index (132.2±16.7% versus 141.4±21.9%; P=0.03) and tended to improve mitochondrial oxidative function.
CONCLUSIONS
NO3(-) increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and VO2. NO3(-) increased exercise vasodilatory and cardiac output reserves. NO3(-) also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling.
CLINICAL TRIAL REGISTRATION URL
www.clinicaltrials.gov. Unique identifier: NCT01919177.
背景
某些蔬菜中富含无机硝酸盐（NO3(-)），其在口腔中被细菌转化为亚硝酸盐。在缺氧情况下，亚硝酸盐可转化为一氧化氮。我们检验了这样一个假设，即补充NO3(-)可通过对运动的特定适应性改变来提高射血分数保留的心力衰竭患者的运动能力。
方法与结果
17名受试者参与了这项随机、双盲、交叉研究，比较单剂量富含NO3(-)的甜菜根汁（NO3(-)，12.9 mmol）与硝酸盐含量相同的安慰剂。受试者进行仰卧位自行车竭尽全力心肺运动试验，测量心输出量和骨骼肌氧合情况。我们还评估了骨骼肌氧化功能。研究终点包括运动效率（总功/总耗氧量）、峰值VO2、总功、血管舒张储备、前臂线粒体氧化功能以及增强指数（动脉波反射标志物，通过桡动脉张力测量法测量）。补充后血浆一氧化氮代谢产物增加（中位数，326对10 μmol/L；P = 0.0003），峰值VO2增加（12.6±3.7对11.6±3.1 mL O2·min(-1)·kg(-1)；P = 0.005），总功增加（55.6±35.3对49.2±28.9 kJ；P = 0.04）。然而，效率未变。运动时，NO3(-)使全身血管阻力的降低幅度更大（-42.4±16.6%对-31.8±20.3%；P = 0.03），心输出量增加幅度更大（121.2±59.9%对88.7±53.3%；P = 0.006）。NO3(-)降低了主动脉增强指数（132.2±16.7%对141.4±21.9%；P = 0.03），并倾向于改善线粒体氧化功能。
结论
NO3(-)通过针对外周异常情况提高了射血分数保留的心力衰竭患者的运动能力。由于总功和VO2平行增加，效率并未改变。NO3(-)增加了运动血管舒张和心输出量储备。NO3(-)还减少了与左心室舒张功能障碍和重塑相关的动脉波反射。
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