The Effects of Acute Intermittent Hypercapnia on Ventilatory and Cardiovascular Plasticity

Abstract

Obstructive sleep apnea (OSA) affects over a third of North Americans and is characterized by intermittent bouts of hypoxia combined with hypercapnia during sleep. Intermittent hypoxia and intermittent hypercapnic hypoxia can elicit long-lasting increases in ventilation, blood pressure, and sympathetic nerve activity in humans and may underpin elevated daytime sympathetic activity observed in OSA patients (i.e., long-term facilitation; LTF). Although cardiorespiratory plasticity to intermittent hypoxia and hypercapnic hypoxia are well studied, it is unknown if intermittent hypercapnia (IHc) in the absence of hypoxia leads to cardiorespiratory plasticity in humans. This study aimed to determine if IHc leads to long-lasting effects on ventilation, blood pressure, and vascular conductance. We hypothesized that IHc would lead to long-lasting effects on ventilation, mean arterial pressure (MAP) and limb vascular conductance. Thirteen healthy participants (age: 23±4 years; BMI: 22±2 kg/m2) underwent a 10-minute baseline, 40-minute IHc protocol (40 seconds end-tidal PCO2 +5 mmHg from baseline and 20 seconds of normocapnia), followed by 30-minutes of recovery. Ventilation and MAP were measured continuously, while arm and leg blood flow were collected at the end of baseline and every 10 minutes throughout recovery (strain gauge plethysmography). Limb vascular conductance was calculated as two times the sum of arm and leg blood flow divided by MAP. Data were compared statistically (P<0.05) using mixed effects linear modeling with time (baseline, 10-, 20-, and 30-minutes recovery) as a fixed factor and participant as a random factor. Ventilation (P=0.05), breathing frequency (P=0.2), and tidal volume (P=0.06) were similar to baseline throughout 30-minutes of recovery. There was a main effect of time for MAP (P<0.001), and post hoc analysis indicated that MAP was increased at 10-minutes (Δ7.2mmHg, CI95%: 3.7 – 10.7, P<0.001), 20-minutes (Δ7.7mmHg, CI95%: 4.2 – 11.2, P<0.001), and 30-minutes (Δ8.6mmHg, CI95%: 5.1 – 12.1, P<0.001) following IHc. There was a main effect of time for limb vascular conductance (P=0.001) and post-hoc analysis showed that conductance was reduced at 10-minutes (Δ0.03mmHg, CI95%: -0.05 – -0.01, P=0.007), 20-minutes (Δ0.03mmHg, CI95%: -0.05 – -0.01, P=0.007), and 30-minutes (Δ0.03mmHg, CI95%: -0.05 – -0.01, P=0.006) following IHc. In conclusion, IHc did not lead to ventilatory plasticity but led to long-term facilitation of arterial pressure and reductions in limb conductance. Thus, intermittent hypercapnia may act synergistically with intermittent hypoxia contributing to daytime sympathoexcitation and elevated blood pressure in conditions such as OSA. Funding Sources: American Physiological Society, Natural Sciences and Engineering Research Council of Canada. 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.