The Tolerability of Resisted Inspiratory Efforts on Cardiopulmonary Pressures and Hemodynamics in Patients with Pulmonary Hypertension

Pulmonary hypertension (PH) is a progressive condition characterized by elevated mean pulmonary arterial pressures (mPAP>20mmHg) which, if left untreated, can progress to right ventricular (RV) failure and death. Resistive breathing protocols have emerged as a therapeutic strategy to reduce common PH symptoms such as dyspnea, exercise intolerance, and respiratory muscle weakness. However, no studies have assessed the effects of resistive breathing on RV preload, nor is it clear whether hemodynamic alterations during these maneuvers are safe and tolerable in the context of PH. Here, we used invasive cardiopulmonary exercise testing (iCPET) to document cardiopulmonary pressures and hemodynamics at rest, throughout a bout of resisted inspiratory efforts (RIE) and a maximal cycling test. Using this approach, we tested the hypothesis that RIE results in transient increases in cardiopulmonary pressures without compromising RV function, as demonstrated by the maintenance of adequate cardiac output reserve immediately following RIE and throughout a subsequent cycling test. Thirteen patients (F:11; age: 59.4±12.2 yrs, mPAP: 28.3±14.6 mmHg) undergoing a clinically indicated iCPET for exertional dyspnea or PH were recruited to the study. Patients performed a bout of RIE (5 sets of 6 breaths at 60% of maximum inspiratory pressure) followed by a maximal cycling test (2-min stages with increasing workload until exhaustion). End-expiratory and respiratory cycle-averaged pressures in the right atrium (RA), pulmonary artery (mPAP) and pulmonary capillary wedge pressure (PCWP; an estimate of left ventricular filling), were obtained at baseline, during RIE, post RIE, during maximal cycling, and in recovery. We used a repeated measures ANOVA with Tukey post hoc tests (p=0.05) to compare cardiopulmonary pressures across baseline, RIE, and post RIE and to compare cardiac output across baseline, post RIE, and maximal cycling. Our analyses show RIE-related increases in RA ( p =0.012), mPAP ( p =0.007), and PCWP ( p =0.026) that return to baseline levels immediately post RIE. There was no change in cardiac output from baseline to post RIE ( p =0.82), however, cardiac output was higher during the cycling test compared to baseline ( p =0.017) and to post-RIE ( p =0.024). Our findings demonstrate that RIE induces elevations in pulmonary and cardiac pressures through enhanced venous return and preload. The rapid normalization of cardiac pressures post RIE combined with preserved cardiac output reserve during the subsequent cycling test indicates the effects are transient and do not result in RV decompensation. These preliminary findings indicate that RIE is safe and well-tolerated by patients with PH. This research was supported by the National Institutes of Health T32 Training Grant (T32HL007249) and R01 Grant (5R01AG065346-05). 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.