Postural hyperventilation in POTS is not driven by exaggerated peripheral chemoreceptor activity

Abstract

BACKGROUND: Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic form of autonomic nervous system dysfunction primarily affecting premenopausal females. POTS patients experience chronic orthostatic symptoms, and a heart rate (HR) increase of ≥30 bpm within 10 min of standing in the absence of orthostatic hypotension (>20/10 mmHg decrease in blood pressure [BP]). On standing, patients can exhibit increased ventilation (VE) with subsequent reductions in end-tidal CO2 (i.e., hypocapnia). Hypocapnia exacerbates tachycardia and symptoms. Previous research has suggested exaggerated peripheral chemoreceptor (pChR) activity drives postural hyperventilation in POTS. OBJECTIVE: We explored exaggerated pChR activity in the pathophysiology of postural hyperventilation in POTS. HYPOTHESIS: We hypothesized that POTS patients have a greater VE reduction during pChR inhibition compared to healthy controls. METHODS: We conducted a randomized crossover trial of hyperoxia vs. normoxia while supine and during head-up tilt (HUT) in 25 POTS patients (F=25; age: 31±8 years) and 12 healthy controls (HC) (F=12; age: 31±6 years; p=0.8). To inhibit pChR, participants breathed 5x30sec bouts of normocapnic hyperoxia (O2: ~400mmHg). Continuous respiratory (VE, ETO2, ETCO2) and hemodynamics (HR, BP, stroke volume, cardiac output, systemic vascular resistance) were measured. Data are reported as mean±SD. Continuous variables were compared using a 3-factor mixed-effects model: [Group: Control vs. Patient] x [Position (repeated measure): supine vs. HUT] x [Gas (repeated measure): ON vs. OFF). RESULTS During normoxic HUT, VE increased relative to supine baseline in both POTS (Supine: 10.3±2.3 L/min, HUT: 15.2±4.2; p<0.001) and HC (Supine: 11.1±2.1 L/min, HUT: 12.9±2.3 L/min; p=0.04). As predicted, the ΔVE in response to HUT was significantly greater in POTS (4.8±3.3 L/min) vs. HC (1.8±1.6 L/min; p=0.001). During HUT, hyperoxia reduced VE in both POTS (p<0.001) and HC (p<0.001). However, the magnitude of the ventilatory inhibition was not different between groups (POTS: -1.9±1.0 L/min; HC: -1.8±1.0 L/min; p=1.0). CONCLUSION: POTS patients have increased postural VE relative to HC. During pChR inhibition with hyperoxia, VE was reduced in both HC and POTS, and the magnitude of ventilatory inhibition in response to hyperoxia was the same in both groups. These findings suggest pChR activity is not exaggerated in POTS patients, and thus is not the primary driver of postural hyperventilation observed in POTS. This work was supported by Standing up to POTS. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.