Centro Cardiologico Monzino-IRCCS, Istituto di Cardiologia, Università di Milano, via Parea 4, 20138, Milan, Italy.
Cardiovasc Drugs Ther. 2009 Oct;23(5):377-84. doi: 10.1007/s10557-009-6195-2.
The present review focuses on the effects of beta-blockers on lung function in HF patients. Indeed, historically, beta-blockers have been considered not indicated in the presence of impaired lung function but recently this concept has been challenged. Lung function abnormalities are part of the chronic HF syndrome, as both lung mechanics and gas exchange are impaired. The regulation of ventilation and gas exchange is under sympathetic control and, therefore, a possible target of beta-blockers. beta-Blocker compounds differ in terms of pharmacological action blocking either both beta1 and beta2 receptors (carvedilol), or selectively the beta1 receptors (nebivolol, bisoprolol, metoprolol). This difference is likely to explain a different action on lung function. Indeed, 90% of beta-receptors in the lung are located on the alveoli and are mainly beta2, whereas 10% are on the airways (mainly beta1-receptors). Expiratory gases and ventilation kinetic analysis during exercise on top of standard spirometry and resting lung diffusion for carbon monoxide (DLCO) provide an integrate evaluation of the respiratory function in HF patients. Carvedilol reduces hyperventilation in HF patients during the entire exercise and proportionally increases patients quality of life. However, carvedilol has a negative action at altitude when, to counterbalance hypoxia, hyperventilation is needed. Indeed, when exercise is performed at a simulated altitude of 2,000 m, PO(2) is 69 +/- 3 mmHg and 64 +/- 4, in placebo and carvedilol, respectively. Mechanical pulmonary function in HF patients at rest and during exercise is only slightly influenced by beta-blockers. beta-Blockers affect DLCO differently in chronic HF. Specifically, carvedilol reduces DLCO from 88 +/- 15% to 74 +/- 13% due to reduction of membrane diffusion, whereas bisoprolol does not influence DLCO, likely due to the absence of action by bisoprolol on alveolar beta2-receptors, which preserve active Na(+) transport processes across the alveolar-capillary membrane. In conclusion, it is possible to use beta-blockers in HF patients even in the presence of lung function impairment, but their use should be guided by a combination of lung function evaluation and knowledge of the pharmacological properties of each molecule.
本文重点介绍了β受体阻滞剂对心力衰竭患者肺功能的影响。事实上，β受体阻滞剂在肺功能受损时曾被认为不适用，但最近这一概念受到了挑战。肺功能异常是慢性心力衰竭综合征的一部分，因为肺力学和气体交换都受到了损害。通气和气体交换的调节受交感神经控制，因此β受体阻滞剂可能是一个潜在的治疗靶点。β受体阻滞剂在药理作用上有所不同，有些可以同时阻断β1和β2受体（卡维地洛），而有些则选择性地阻断β1受体（比索洛尔、奈必洛尔、美托洛尔）。这种差异可能解释了它们对肺功能的不同作用。事实上，肺内 90%的β受体位于肺泡，主要是β2受体，而 10%位于气道（主要是β1受体）。在标准肺功能检查和一氧化碳弥散量（DLCO）的基础上，进行运动时呼气气体和通气动力学分析，可对心力衰竭患者的呼吸功能进行综合评估。卡维地洛可减少心力衰竭患者在整个运动过程中的过度通气，并相应提高患者的生活质量。然而，卡维地洛在高海拔地区时会产生负面影响，因为为了对抗缺氧，需要过度通气。事实上，当在模拟海拔 2000 米的高度进行运动时，PO2 分别为 69 +/- 3 mmHg 和 64 +/- 4 mmHg，在安慰剂和卡维地洛组中。β受体阻滞剂对心力衰竭患者静息和运动时的肺机械功能仅有轻微影响。β受体阻滞剂对慢性心力衰竭患者的 DLCO 影响不同。具体来说，卡维地洛将 DLCO 从 88 +/- 15%降低至 74 +/- 13%，这是由于膜扩散减少所致，而比索洛尔则不影响 DLCO，这可能是由于比索洛尔对肺泡β2受体没有作用，而β2受体可以维持肺泡-毛细血管膜上的主动钠转运过程。总之，即使心力衰竭患者肺功能受损，也可以使用β受体阻滞剂，但应结合肺功能评估和对每种分子药理特性的了解来指导其使用。
