Expiratory flow limitation during exercise: why does it ‘suck’ so much?

Expiratory flow limitation (EFL) is a mechanical ventilatory constraint that mediates exercise intolerance, breathlessness and altered respiratory mechanics in healthy and clinical populations, including chronic obstructive pulmonary disease (COPD; Babb, 2013). A significant amount of research has focused upon these important aspects of EFL, but one group has hypothesized that in COPD, EFL might impact central haemodynamics, whereby excessive expiratory pressures cause movement of blood from the thorax to the extremities. This would create a vicious cycle of decreasing pulmonary blood volume, increasing dead space ventilation, exacerbating hypercapnia, driving further increases in expiratory pressure (Iandelli et al., 2002), and so on. Their previous work (Iandelli et al., 2002) has confirmed this hypothesis indirectly, using externally imposed EFL in healthy individuals exercising maximally, suggesting that large expiratory muscle pressures propelled blood from the thorax to the extremities. In this issue of The Journal of Physiology, Stucky et al. (2023) pursued this intriguing hypothesis with an experimental and measurement protocol that allowed for indirect measurement of fluid shifts in healthymen using double plethysmography and externally imposed EFL during submaximal exercise to mimic a ventilation that can be achieved by COPD patients. They report a net movement of fluid into the thorax, which was more related to the negative oesophageal pressure during inspiration than to the greater gastric pressure during expiration, which is in contrast with their prior work. They demonstrate that, sometimes, EFL ‘sucks’ the blood into the thorax. This is an exceptionally interesting and well-conducted study with a new experimental and measurement protocol, but has some limitations that are worth noting. Their unique measurement set-up allowed for a relatively low exercise intensity, which is likely to have prevented them from observing gastric pressure values during expiration that parallel those observed in clinical populations, such as COPD. Likewise, their set-up presented some ‘environmental’ concerns that required the measurement period to be short (3 min), which prevents us from understanding what might have occurred to blood shifts during steady-state exercise. Although Stucky et al. (2023) discuss their findings primarily within the context of COPD, we cannot help but consider how their findings might apply to other diseases in which EFL is highly prevalent yet cardiac mechanics and/or the pulmonary vasculature are severely impaired. One such example of this mixed pathology is left heart failure with reduced ejection fraction (HFrEF). Certainly, it is common to observe that HFrEF patients experience EFL during submaximal exercise. According to Stucky et al. (2023), we might, at first, expect that if expiratory gastric pressure swings are modest with respect to the increasingly negative oesophageal pressure during inspiration, the occurrence of EFL during submaximal exercise would promote a shift in blood volume from the extremities towards the trunk in these patients. Likewise, one might expect, at least in the healthy adult, an increased venous return to enhance left ventricular output over time; the promise of enhanced cardiac output in exercising HFrEF patients is thereafter self-explanatory. However, the pulmonary vascular pathologies commensurate with HFrEF (Lalande et al., 2020) might increase right heart filling pressures and volumes, thereby positioning the operating point of the right ventricle on the flatter, less compliant portion of the Frank–Starling curve. Moreover, a dilated right ventricle would alter left heart filling via a leftward shift of the interventricular septum and transmission of stress through stretching of the pericardium. Broadly speaking, one might regard the left ventricle of the HFrEF patient to be less sensitive to variations in preload, and thus more sensitive to fluctuations in afterload (Lalande et al., 2020). Here, a centralization of blood volume secondary to mild EFL during exercise could instead worsen an already impaired left ventricular output during exercise in HFrEF(!). The reality is that HFrEF patients are unlikely to present with EFL on exertion that produces only mild increases in expiratory gastric pressure. Their increased ventilatory demand (i.e. hyperventilation) and higher expiratory resistive work of breathing conspire to produce excessive expiratory pressures at even the most modest of exercise intensities (i.e. ventilation >20 L min−1). On this point, we have previously argued that EFL might even help (rather than hinder) the cardiac response to exercise in HFrEF; that is, the high positive intrathoracic pressures generated by EFL in HFrEF lead to a reduction in transmural stress acting across the left ventricular wall (i.e. decreased afterload), ultimately shifting the operating point where the left ventricle lies on the Frank–Starling curve towards higher stroke volumes (Cross et al., 2020). This thesis must, of course, be tempered by observations that inspiratory muscle work and, consequently, negative oesophageal pressure swings are also augmented in HFrEF during exercise. Consequently, it is also possible that the predominant effect of EFL in HFrEF might, after all, present much like that observed by Stucky et al. (2023) in healthy adults with externally imposed EFL during submaximal exercise. At this juncture, one is reminded of the insight offered in the recent work of Stucky et al. (2023) that the resultant effect of EFL on blood volume shifts during exercise is extremely nuanced, insofar as it depends on the balance of competing intrathoracic pressure gradients established during inspiration (‘sucking’ of blood into the trunk) and expiration (‘pushing’ of blood towards the extremities). Does EFL really ‘suck’ that much? Or does it simply want to push your blood to the extremities? The findings of Stucky