Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milano, Italy.
PLoS One. 2013 Apr 16;8(4):e61877. doi: 10.1371/journal.pone.0061877. Print 2013.
In experimental conditions alveolar fluid clearance is controlled by alveolar β2-adrenergic receptors. We hypothesized that if this occurs in humans, then non-selective β-blockers should reduce the membrane diffusing capacity (DM), an index of lung interstitial fluid homeostasis. Moreover, we wondered whether this effect is potentiated by saline solution infusion, an intervention expected to cause interstitial lung edema. Since fluid retention within the lungs might trigger excessive ventilation during exercise, we also hypothesized that after the β2-blockade ventilation increased in excess to CO2 output and this was further enhanced by interstitial edema.
22 healthy males took part in the study. On day 1, spirometry, lung diffusion for carbon monoxide (DLCO) including its subcomponents DM and capillary volume (VCap), and cardiopulmonary exercise test were performed. On day 2, these tests were repeated after rapid 25 ml/kg saline infusion. Then, in random order 11 subjects were assigned to oral treatment with Carvedilol (CARV) and 11 to Bisoprolol (BISOPR). When heart rate fell at least by 10 beats·min(-1), the tests were repeated before (day 3) and after saline infusion (day 4). CARV but not BISOPR, decreased DM (-13 ± 7%, p = 0.001) and increased VCap (+20 ± 22%, p = 0.016) and VE/VCO2 slope (+12 ± 8%, p<0.01). These changes further increased after saline: -18 ± 13% for DM (p<0.01), +44 ± 28% for VCap (p<0.001), and +20 ± 10% for VE/VCO2 slope (p<0.001).
These findings support the hypothesis that in humans in vivo the β2-alveolar receptors contribute to control alveolar fluid clearance and that interstitial lung fluid may trigger exercise hyperventilation.
在实验条件下，肺泡液体清除受肺泡β2-肾上腺素能受体控制。我们假设，如果这种情况发生在人类身上，那么非选择性β受体阻滞剂应该会降低膜弥散能力（DM），这是肺间质液稳态的一个指标。此外，我们想知道这种效应是否会因盐水输注而增强，这种干预措施预计会导致间质肺水肿。由于肺部的液体潴留可能会在运动期间引发过度通气，我们还假设在β2-受体阻断后，通气量超过 CO2 输出，并且间质水肿会进一步增强这种情况。
22 名健康男性参加了这项研究。在第 1 天，进行了肺活量测定、一氧化碳肺弥散（DLCO），包括其亚组分 DM 和毛细血管容积（VCap），以及心肺运动试验。在第 2 天，在快速输注 25ml/kg 盐水后重复这些测试。然后，随机将 11 名受试者分配到口服卡维地洛（CARV）治疗组，11 名受试者分配到比索洛尔（BISOPR）治疗组。当心率至少下降 10 次/分时，在盐水输注前（第 3 天）和输注后（第 4 天）重复这些测试。CARV 而非 BISOPR，降低了 DM（-13±7%，p=0.001），增加了 VCap（+20±22%，p=0.016）和 VE/VCO2 斜率（+12±8%，p<0.01）。这些变化在盐水输注后进一步增加：DM 减少-18±13%（p<0.01），VCap 增加+44±28%（p<0.001），VE/VCO2 斜率增加+20±10%（p<0.001）。
这些发现支持这样一种假设，即在人类体内，β2-肺泡受体有助于控制肺泡液体清除，间质肺液可能会引发运动性过度通气。
