Slow deep breathing acutely improves breathing efficiency and reduces muscle sympathetic nerve activity in pulmonary hypertension

The sympathetic nervous system is overactive in pulmonary arterial hypertension (PAH) and associated with worsened exercise capacity and clinical outcomes. Muscle sympathetic nerve activity (MSNA) is coupled with respiration in humans, such that MSNA is inhibited at high lung volumes compared to low lung volumes. Slow deep breathing (SDB) enhances this coupling and has been observed to acutely reduce MSNA in some studies of heart failure and hypertension patients. We aimed to assess the effect of SDB on MSNA and hypothesised that SDB would reduce MSNA in PH (PAH and chronic thromboembolic hypertension [CTEPH]). Nine PAH and 1 CTEPH patients (6 female; age 54±15 years; mean±SD) were recruited and cardiorespiratory parameters and MSNA (peroneal nerve microneurography; n=9) measured before (baseline period; 10 min) and during SDB (SDB period; 5 min). SDB involved the volitional control of breathing at 6 breaths per minute with an inspiratory to expiratory ratio of 1:2, without control of tidal volume (V T ). MSNA was stratified by lung volume (high lung volume defined as being above the mean V T of the period and low lung volume below) and the respiratory modulation of MSNA defined as the percentage change in MSNA from low to high lung volume. Comparisons between baseline and SDB were made using Student’s paired t- test. SDB increased V T (2.0±0.5 vs. 0.8±0.3 L; p=0.002) whilst ventilation (V· E ) was unchanged (13±3 vs. 13±3 L·min -1 ; p=0.770). SDB reduced partial pressure of end-tidal carbon dioxide (33±5 vs. 36±5 mmHg; p=0.023), increased partial pressure of end-tidal oxygen (115±11 vs. 107±7 mmHg; p=0.004), increased oxygen saturation (97±3 vs. 95±3 %; p=0.002), and decreased mean arterial pressure (90±11 vs. 94±13 mmHg; p=0.041). SDB reduced MSNA burst incidence (43±16 vs. 49±17 bursts per 100 heart beats; p=0.007) and tended to reduce burst frequency (28±9 vs. 31±8 bursts per min; p=0.066), whilst MSNA total activity was unchanged (1233±785 vs. 1266±631 au; p=0.722). Notably, SDB enhanced the respiratory suppression of MSNA at high lung volumes (∆burst incidence -66±17 vs. -34±17 %; p<0.001). In summary, SDB in PH acutely improves gas exchange despite unchanged V· E (i.e., improved ventilatory efficiency), lowers MSNA and enhances the respiratory modulation of MSNA, supporting further investigation of SDB as a therapy to improve breathing efficiency and sympathetic overactivity in PH. Heart Lung Foundation (formerly Greenlane Research and Educational Fund; Ref# 21/01/4153; M.J.P, J.F.R.P, S.S, and J.P.F) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.