Breathing new life into the respiratory pump

Cervical spinal cord injury (C-SCI) is associated with impaired cardiorespiratory function. Several factors are thought to contribute to impaired cardiac function in C-SCI resulting in a blunted stroke volume response to exercise (Hostettler et al., 2012), and a corresponding reduction in maximal oxygen consumption as compared to able-bodied controls (Gee et al., 2021). While inspiratory muscle strength is relatively well maintained, C-SCI results in impaired expiratory muscle function and altered abdominal and chest wall compliance such that exercise in C-SCI is associated with dynamic hyperinflation and the related tachypnoeic breathing pattern (Gee et al., 2021). Surprisingly, unlike what is observed in respiratory patients who also show hyperinflation with exercise, individuals with C-SCI do not appear to have profound expiratory flow limitation during exercise (Taylor et al., 2010) and maintain an appropriate hyperventilatory response up to peak exercise. In a paper in this issue of The Journal of Physiology, Gee and colleagues (2022) hypothesize that by manipulating the intrathoracic pressure swings and enhancing the respiratory pump, left-ventricular (LV) filling and cardiac output may be increased in C-SCI, and that this approach could eventually be used as a potential mechano-therapeutic target to enhance cardiovascular function during exercise in C-SCI. Using inspiratory and expiratory loading, Gee et al. (2022) examined whether augmenting the respiratory pump at rest in the 45° head-up tilt position altered LV filling and cardiac output in individuals with C-SCI, and compared the responses to an able-bodied reference group. Expiratory loading resulted in hyperinflation and reduced LV end-diastolic volume in C-SCI, while no changes were observed in the reference group. Stroke volume was unchanged in CSCI with expiratory loading as there was a compensatory reduction in end-systolic volume. As C-SCI individuals demonstrate an impaired cardiac response with exercise (Hostettler et al., 2012), it is unclear if a similar compensatory response in end-systolic volume would be observed during exercise. Contrary to their original hypothesis, however, inspiratory loading did not affect LV filling or cardiac output in either C-SCI or the able-bodied reference group. The paper by Gee and colleagues (2022) is an elegant study that not only seeks to understand cardiopulmonary physiology in an under-studied group, but also provides unique insight into fundamental physiology. The blunted cardiac output response to exercise in C-SCI is physiologically important as it impacts exercise tolerance, and countless studies in other conditions have shown that impaired exercise tolerance is associated with clinically important outcomes such as increased dyspnoea and reduced quality of life. Thus, the paper makes a critical attempt to examine both a potential mechanism and treatment for the reduced cardiac output response to exercise in C-SCI. The significance of the respiratory pump in contributing to cardiac filling/function has been an area of interest for physiologists for many years. Following C-SCI, there is likely loss of supraspinal sympathetic control of the peripheral veins. From a basic cardiopulmonary physiology perspective, this provides a fascinating model to examine the isolated impact of the ‘respiratory pump’ on LV function in humans. That −20 cmH20 inspiratory pressure loading had no impact on LV end-diastolic volume in either C-SCI or able-bodied participants suggests that even large inspiratory pressure swings are unlikely to significantly impact cardiac filling/function in the healthy heart while in the 45° head-up tilt position. Gee et al. (2022), as well as the research participants, are to be commended for completing this difficult study that included intra-thoracic monitoring with oesophageal balloons and determination of operating lung volumes, all the while maintaining end-tidal carbon dioxide values and obtaining cardiac ultrasound images across five breathing conditions. Expiratory loading led to a reduction in LV end-diastolic volume, and the authors rationalize that the reduced end-diastolic volume is likely explained by an increase in right atrial pressure and a reduced gradient for venous return. However as pointed out by the authors, expiratory loading also resulted in lung hyperinflation, which could also contribute to the reduced end-diastolic volume with expiratory loading. Indeed previous work from the authors’ group has shown that alleviating hyperinflation in C-SCI with abdominal binding can improve exercise tolerance (West et al., 2014). While difficult to execute, in follow-up studies it would be ideal to separate the independent effects of lung hyperinflation from expiratory loading in C-SCI. The paper by Gee and colleagues (2022) serves as an exemplar of an impactful modern physiological paper that not only seeks to understand critical mechanism(s) of exercise intolerance in an under-studied population, but also provides fascinating insight into basic cardiopulmonary physiology. We look forward to continued work by this group examining mechanisms and potential therapies for impaired cardiovascular function and exercise intolerance in C-SCI.