Physiological insights of exercise hyperventilation in arterial and chronic thromboembolic pulmonary hypertension

Background: Pulmonary hypertension (PH) patients show, during exercise, an excessive increase in ventilation (VE) compared to carbon dioxide output (VCO2), determining a high VE/VCO2 slope. There are several possible causes, including an elevated dead space ventilation (VD), VE/perfusion (Q) mismatch and/or an enhanced peripheral or central chemoreceptor activity. We evaluated the causes of exercise hyperventilation in PH patients. Methods: Eighteen group I and IV PH patients underwent cardiopulmonary exercise test with blood gas analysis at every minute. VE, alveolar ventilation (VA) and VD vs. VCO2 relationship were calculated. Resting chemoreceptor sensitivity was analyzed through hypoxia/hypercapnia tests. Results: PeakVO2 and VE/VCO2 slopes were 1.06 ± 0.24 l/min and 39.1 ± 9.0, respectively. Throughout the exercise, 30% of VE was due to VD. VE/VCO2 slope significantly correlated with VD/VCO2 slope (r = 0.82, p < 0.001) but not with VA/VCO2 slope (r = 0.3, p = ns). Peak exercise end-tidal CO2 (PetCO2) correlated with VD/VCO2 slope (r = − 0.79, p < 0.001) and VE/VCO2 slope (r = − 0.91, p < 0.001). Dead space(DS)/Tidal volume and P(arterial-et)CO2 were elevated without arterial hypoxemia suggesting a high VE/Q mismatch. Chemoreceptor peripheral response to hypoxia and central CO2 response were both enhanced being peripheral responses to hypoxia and hypercapnia 0.416 ± 0.402 (normal ref values = 0.285 ± 0.221) l/min/O2Sat and 0.076 ± 0.047 (0.066 ± 0.430) l/min/mmHg, respectively; central hypercapnic chemosensitivity was 4.475 ± 3.99 (2.352 ± 0.936) l/min/mmHg. Conclusions: Increased DS, VE/Q mismatch and chemorecptor response are among the main mechanisms involved in exercise hyperventilation in PH. ClinicalTrial.gov NCT02892981.