Cazzola Mario, Mantero Antonio, Santus Pierachille, Carlucci Paolo, Mondoni Michele, Bosotti Laura, Centanni Stefano
Unit of Pneumology and Allergology, A. Cardarelli Hospital, Via del Parco Margherita 24, 80121 Napoli, Italy.
Pulm Pharmacol Ther. 2007;20(3):258-64. doi: 10.1016/j.pupt.2006.02.002. Epub 2006 Mar 6.
Increase in pulmonary artery pressure (PAP), which is common in severe chronic obstructive pulmonary disease (COPD), is a predictor of mortality independent of airflow limitation. beta-agonists might slightly attenuate this increase because they exert a vasodilating effect on pulmonary circulation when systematically administered. We have investigated the acute effects of salmeterol and formoterol on echocardiographic systolic pulmonary artery pressure (sPAP) in 20 patients with COPD and a sPAP greater than 20mmHg at rest. Acute haemodynamic responses to inhaled formoterol or salmeterol were assessed in all patients, in a randomized, double-blind double-dummy fashion. On two consecutive days, patients received, in a randomized order, formoterol 12microg via Turbuhaler plus placebo via Diskus or salmeterol 50microg via Diskus plus placebo via Turbuhaler. Transthoracic Doppler echocardiography measurements of sPAP were made before and 15, 30, 60 and 180min after bronchodilator inhalation. Lung function, pulse oximetry and heart rate were also monitored at the same times. Mean sPAP significantly (p<0.05) decreased in comparison with baseline at 15, 30, and 60min post inhalation but returned towards control levels at 180min after both salmeterol and formoterol. There was no correlation between the maximum increase in FEV(1) and maximum decrease in sPAP either after inhalation of salmeterol (r(2)=0.071) or after that of formoterol (r(2)=0.0006). The increases in FEV(1) in comparison with baseline were always significant (p<0.05) from 15 to 180min post inhalation after either salmeterol or formoterol. Neither pulse oximetry nor heart rate changed in a significant manner (p>0.05). This study demonstrated that salmeterol and formoterol were equally beneficial for pulmonary haemodynamics in patients with COPD. A direct vasodilatation due to the activation of beta-adrenoceptors that are present in pulmonary vessels is a likely mechanism of their action in inducing the decrease in sPAP.
肺动脉压（PAP）升高在重度慢性阻塞性肺疾病（COPD）中很常见，它是独立于气流受限的死亡预测指标。β受体激动剂可能会略微减轻这种升高，因为系统给药时它们对肺循环有血管舒张作用。我们研究了沙美特罗和福莫特罗对20例静息时收缩期肺动脉压（sPAP）大于20mmHg的COPD患者超声心动图测定的sPAP的急性影响。所有患者均以随机、双盲双模拟方式评估吸入福莫特罗或沙美特罗后的急性血流动力学反应。在连续两天中，患者以随机顺序接受通过都保吸入12μg福莫特罗加通过准纳器吸入安慰剂，或通过准纳器吸入50μg沙美特罗加通过都保吸入安慰剂。在支气管扩张剂吸入前以及吸入后15、30、60和180分钟进行经胸多普勒超声心动图测量sPAP。同时还监测肺功能、脉搏血氧饱和度和心率。吸入后15、30和60分钟时，平均sPAP与基线相比显著降低（p<0.05），但在吸入沙美特罗和福莫特罗后180分钟时又恢复到对照水平。吸入沙美特罗后（r²=0.071）或福莫特罗后（r²=0.0006），FEV₁的最大增加与sPAP的最大降低之间均无相关性。吸入沙美特罗或福莫特罗后，与基线相比，FEV₁从吸入后15至180分钟始终显著增加（p<0.05）。脉搏血氧饱和度和心率均无显著变化（p>0.05）。本研究表明，沙美特罗和福莫特罗对COPD患者的肺血流动力学同样有益。肺血管中存在的β肾上腺素能受体激活导致的直接血管舒张可能是它们诱导sPAP降低的作用机制。
