Abstract

A sustained elevation in respiratory drive following removal of a stimulus is known as respiratory long-term facilitation (rLTF). This phenomenon has been well demonstrated in humans and other animals following intermittent hypoxia. Potential clinical benefits of enhancing respiratory drive with intermittent hypoxia are likely to be offset by its side effects. However, intermittent negative airway pressure (INAP) has recently been shown in rats to elicit a similar magnitude of rLTF as IH but could have fewer side effects. We investigated whether INAP elicits rLTF in awake humans. 13 healthy male volunteers (20.9 ± 2.8 years) undertook two trials (INAP and Control). In the INAP trial, participants were exposed to one hour of 30-second episodes of negative pressure (-10 cmH 2 O) interspersed by 60-second intervals of atmospheric pressure. In the Control trial, participants breathed at atmospheric pressure for one hour. Changes in ventilation were assessed by comparing ventilation during the final five minutes of a 20-minute baseline period, with the final five minutes of a one-hour recovery period. In the Control trial ventilation increased from 14.7 ± 0.8 L/min during baseline to 16.9 ± 0.9 L/min in recovery (P=0.023). However, in the INAP trial ventilation increased significantly more (P=0.019) between baseline and recovery (14.9 ± 0.9 vs 19.1 ± 0.7 L/min, P=0.002). Data shown as mean ± SEM. In this study INAP elicits rLTF in awake, healthy humans. Further research is required to investigate the responsible mechanisms and determine if this form of rLTF could benefit patients with respiratory insufficiency.

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