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

Pulmonary hypertension (PH) patients show, during exercise, an excessive increase in ventilation (V_E) compared to carbon dioxide output (VCO₂), determining a high V_E/VCO₂ 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.

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. VCO₂ relationship were calculated. Resting chemoreceptor sensitivity was analyzed through hypoxia/hypercapnia tests.

PeakVO₂ and V_E/VCO₂ 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/VCO₂ slope significantly correlated with V_D/VCO₂ slope (r=0.82, p<0.001) but not with V_A/VCO₂ slope (r=0.3, p=ns). Peak exercise end-tidal CO₂ (PetCO₂) correlated with V_D/VCO₂ slope (r=-0.79, p<0.001) and V_E/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 V_E/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.

Increased DS, V_E/Q mismatch and chemorecptor response are among the main mechanisms involved in exercise hyperventilation in PH. ClinicalTrial.govNCT02892981.