CO 2 Effects on Intermittent Hypoxia‐Induced Respiratory Motor Plasticity in Humans: In Progress Study

Abstract

Intermittent hypoxia (IH) elicits respiratory motor plasticity (known as ventilatory long-term facilitation [LTF]) in humans and other mammals. However, awake humans exhibit ventilatory LTF only when CO2 levels are raised slightly above eupneic levels in a sustained or intermittent fashion during the IH protocol. In this ongoing study, we seek to determine the effect of CO2 on IH-induced respiratory motor plasticity by examining multiple, distinct mechanisms contributing to the ventilatory response during and following acute intermittent hypercapnic hypoxia (IHH). We hypothesized that IHH elicits a prolonged increase in cortico-diaphragmatic conduction, resting neural drive to breathe, and respiratory motor output versus poikilocapnic IH and a normoxic, normocapnic control (CTRL). Five healthy young adults (age = 32 ± 5 years; 3 female) completed four study visits. Day 1 consisted of general subject characterization. On Days 2, 3 and 4 (separated by ≥72 h), subjects were randomly assigned to receive either: IHH (PETO2 = 55 ± 4 Torr, PETCO2 = 44 ± 3 Torr), IH (PETO2 = 55 ± 3 Torr, PETCO2 = 37 ± 2 Torr), or CTRL (PETO2 = 107 ± 3 Torr, PETCO2 = 36 ± 2 Torr). Protocols consisted of 15 episodes of 60 s exposure with 90 s breathing ambient room air. Cardiovascular responses (heart rate, blood pressure and oxygen saturation) were monitored throughout. Cortico-diaphragmatic conduction was quantified by recording motor evoked potentials (MEPs) using transcranial magnetic stimulation and surface EMG electrodes. Resting neural drive to breathe was assessed using the mouth occlusion pressure technique (i.e. P0.1). Respiratory motor output was measured as minute ventilation () during resting isocapnic conditions (PETCO2 maintained within 1 mmHg of baseline) and adjusted based on the rate of metabolic CO2 production (/). Dependent variables were assessed at baseline, and 30-60 min post. Following IHH, IH and CTRL, the mean change in MEP amplitude was +34 ± 48%, +9 ± 21%, and +2 ± 22%; the mean change in P0.1 was +26 ± 17%, +15 ± 16%, and +7 ± 16%; and the mean change in was +0.3 ± 1.0 L·min-1, +0.3 ± 1.1 L·min-1, and +0.3 ± 0.8 L·min-1. When adjusted for , the mean change in / was -0.5 ± 1.0, +0.4 ± 1.8, and -0.2 ± 1.1. Based on these preliminary data in 5 subjects, we suggest that IHH elicits greater increases in cortico-diaphragmatic conduction and resting neural drive to breathe vs. poikilocapnic IH and CTRL. Conversely, our IHH protocol does not elicit ventilatory LTF. We reason that measures such as MEP amplitude and P0.1 are less sensitive to behavioral influences vs. , and may provide unique insights into mechanisms of IH-induced respiratory motor plasticity in awake healthy humans.