Wales Heart Research Institute, Cardiff University Medical School, Cardiff, United Kingdom.
J Am Coll Cardiol. 2013 Jun 25;61(25):2534-41. doi: 10.1016/j.jacc.2013.03.050. Epub 2013 Apr 23.
The aim of this study was to assess the potential benefits of inorganic nitrite in 2 clinical models: stress-induced myocardial ischemia and whole-arm ischemia-reperfusion.
Inorganic nitrite, traditionally considered a relatively inert metabolite of nitric oxide, may exert vasomodulatory and vasoprotective effects. Despite promising results from animal models, few have shown effectiveness in human model systems, and none have fully translated to the clinical setting.
In 10 patients with inducible myocardial ischemia, saline and low-dose sodium nitrite (NaNO₂) (1.5 μmol/min for 20 min) were administered in a double-blind fashion during dobutamine stress echocardiography, at separate visits and in a random order; long-axis myocardial function was quantified by peak systolic velocity (Vs) and strain rate (SR) responses. In 19 healthy subjects, flow-mediated dilation was assessed before and after whole-arm ischemia-reperfusion; nitrite was given before ischemia or during reperfusion.
Comparing saline and nitrite infusions, Vs and SR at peak dobutamine increased in regions exhibiting ischemia (Vs from 9.5 ± 0.5 cm/s to 12.4 ± 0.6 cm/s, SR from -2.0 ± 0.2 s(-1) to -2.8 ± 0.3 s(-1)), whereas they did not change in normally functioning regions (Vs from 12.6 ± 0.4 cm/s to 12.6 ± 0.6 cm/s, SR from -2.6 ± 0.3 s(-1) to -2.3 ± 0.1 s(-1)) (p < 0.001, analysis of variance). With NaNO2, the increment of Vs (normalized for increase in heart rate) increased only in poorly functioning myocardial regions (+122%, p < 0.001). Peak flow-mediated dilation decreased by 43% after ischemia-reperfusion when subjects received only saline (6.8 ± 0.7% vs. 3.9 ± 0.7%, p < 0.01); administration of NaNO2 before ischemia prevented this decrease in flow-mediated dilation (5.9 ± 0.7% vs. 5.2 ± 0.5%, p = NS), whereas administration during reperfusion did not.
Low-dose NaNO₂ improves functional responses in ischemic myocardium but has no effect on normal regions. Low-dose NaNO₂ protects against vascular ischemia-reperfusion injury only when it is given before the onset of ischemia.
本研究旨在评估无机亚硝酸盐在 2 种临床模型中的潜在益处：应激诱导性心肌缺血和全臂缺血再灌注。
无机亚硝酸盐，传统上被认为是一氧化氮的相对惰性代谢物，可能具有血管调节和血管保护作用。尽管动物模型的结果很有希望，但在人体模型系统中显示有效性的却很少，而且没有一个完全转化为临床环境。
在 10 名可诱导性心肌缺血患者中，在多巴酚丁胺超声心动图检查期间，以双盲方式在不同时间和随机顺序分别给予生理盐水和低剂量亚硝酸钠（NaNO₂）（1.5 μmol/min 持续 20 分钟）；通过峰值收缩速度（Vs）和应变率（SR）反应定量评估长轴心肌功能。在 19 名健康受试者中，在全臂缺血再灌注之前和之后评估血流介导的扩张；在缺血前或再灌注期间给予亚硝酸盐。
与生理盐水输注相比，在出现缺血的区域，Vs 和 SR 在峰值多巴酚丁胺时增加（Vs 从 9.5 ± 0.5 cm/s 增加至 12.4 ± 0.6 cm/s，SR 从 -2.0 ± 0.2 s(-1) 增加至 -2.8 ± 0.3 s(-1)），而在正常功能区域则没有变化（Vs 从 12.6 ± 0.4 cm/s 增加至 12.6 ± 0.6 cm/s，SR 从 -2.6 ± 0.3 s(-1) 增加至 -2.3 ± 0.1 s(-1)）（p < 0.001，方差分析）。用 NaNO2 时，仅在功能不良的心肌区域，Vs 的增加（按心率增加的百分比归一化）增加了 122%（p < 0.001）。当受试者仅接受生理盐水时，缺血再灌注后峰值血流介导的扩张减少了 43%（6.8 ± 0.7%对 3.9 ± 0.7%，p < 0.01）；在缺血前给予 NaNO2 可防止这种血流介导的扩张减少（5.9 ± 0.7%对 5.2 ± 0.5%，p = NS），而在再灌注期间给予则没有。
低剂量 NaNO₂可改善缺血心肌的功能反应，但对正常区域没有影响。低剂量 NaNO₂仅在给药前开始缺血时才能防止血管缺血再灌注损伤。
