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

Abstract Background Pulmonary hypertension (PH) patients show, during exercise, an excessive increase in ventilation (V E ) compared to carbon dioxide output (VCO 2 ), determining a high V E /VCO 2 slope. There are several possible causes, including an elevated dead space ventilation (V D ), V E /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. V E , alveolar ventilation (V A ) and V D vs. VCO 2 relationship were calculated. Resting chemoreceptor sensitivity was analyzed through hypoxia/hypercapnia tests. Results PeakVO 2 and V E /VCO 2 slopes were 1.06±0.24l/min and 39.1±9.0, respectively. Throughout the exercise, 30% of V E was due to V D . V E /VCO 2 slope significantly correlated with V D /VCO 2 slope (r=0.82, p A /VCO 2 slope (r=0.3, p=ns). Peak exercise end-tidal CO 2 (PetCO 2 ) correlated with V D /VCO 2 slope (r=−0.79, p E /VCO 2 slope (r=−0.91, p 2 were elevated without arterial hypoxemia suggesting a high V E /Q mismatch. Chemoreceptor peripheral response to hypoxia and central CO 2 response were both enhanced being peripheral responses to hypoxia and hypercapnia 0.416±0.402 (normal ref values=0.285±0.221) l/min/O 2 Sat 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, V E /Q mismatch and chemorecptor response are among the main mechanisms involved in exercise hyperventilation in PH. ClinicalTrial.gov NCT02892981