Blunted hypoxic pulmonary vasoconstriction in apnoea divers

Abstract

Competitive apnoea divers dive repetitively to depths >50 m. During the final portions of ascent, divers experience significant hypoxaemia. Additionally, hyperbaria during diving increases thoracic blood volume while simultaneously reducing lung volume and increasing pulmonary artery pressure. We hypothesized that divers would have exaggerated hypoxic pulmonary vasoconstriction, leading to increased right heart work owing to their repetitive hypoxaemia and hyperbaria, and that the administration of sildenafil would have a greater effect in reducing pulmonary resistance in divers. We recruited 16 divers (Divers) and 16 age-and sex-matched non-diving control subjects (Controls). Using a double-blinded, placebo-controlled, cross-over design, participants were evaluated for normal cardiac and lung function, then their cardiopulmonary responses to 20-30 min of isocapnic hypoxia (end-tidal partial pressure of O 2 = 50 mmHg) were measured 1 h after ingestion of 50 mg sildenafil or placebo. Cardiac structure and cardiopulmonary function were similar at baseline. With placebo, Divers had a significantly smaller increase in total pulmonary resistance than Controls after 20-30 min isocapnic hypoxia (change −3.85 ± 72.85 vs. 73.74 ± 91.06 dyns cm −5 , P = 0.0222). With sildenafil, Divers and Controls had similar blunted increases in total pulmonary resistance after 20-30 min of hypoxia.Divers also had a significantly lower systemic vascular resistance after sildenafil in normoxia. These data indicate that repetitive apnoea diving leads to a blunted hypoxic pulmonary vasoconstriction. We suggest that this is a beneficial adaption allowing for increased cardiac output with reduced right heart work and thus reducing cardiac oxygen utilization in hypoxaemic conditions.

A song of iron and oxygen: Hypoxic pulmonary vasoconstriction and gas exchange in chronic obstructive pulmonary disease

“…There is a renewed interest in the mechanisms and (mal)adaptability of HPV in humans, highlighted in recent publications focused on static apnoea and high-altitude acclimatization (Jernigan et al, 2021;Kelly et al, 2022;Subedi et al, 2022). These studies have confirmed the modulatory significance of iron on HPV, providing clues to the limits of physiological adaptation to terrestrial extremes that have translational relevance for mechanisms of disease.…”

“…HPV also plays important roles postnatally in relationship to several extreme physiological and clinical phenomena, helping to restore the matching of pulmonary perfusion to ventilation when hypoxic regions in the lung develop. There is a renewed interest in the mechanisms and (mal)adaptability of HPV in humans, highlighted in recent publications focused on static apnoea and high‐altitude acclimatization (Jernigan et al., 2021 ; Kelly et al., 2022 ; Subedi et al., 2022 ). These studies have confirmed the modulatory significance of iron on HPV, providing clues to the limits of physiological adaptation to terrestrial extremes that have translational relevance for mechanisms of disease.…”