Respiratory effects of beta-blocker therapy in heart failure

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.