Respiratory Long-Term Facilitation: Too Much or Too Little of a Good Thing?

Respiratory long-term facilitation (LTF), a prolonged augmentation of respiratory motor output, is induced by intermittent hypoxia in anesthetized or sleeping rats (and humans in limited conditions). Whether such augmentation in the controller response is of physiological benefit in terms of ventilatory stability remains uncertain; its impact on ventilatory stability will be determined to some extent by its effects on CO₂ chemoreflex loop gain. We used integrated nerve responses in a rat model of LTF to assess chemoreflex parameters related to breathing stability. In this model, LTF decreases chemoreflex threshold but increases chemoreflex gain. Whereas a decreased chemoreflex threshold would promote ventilatory stability, increased chemoreflex gain represents a destabilizing influence. Based on these considerations alone, the impact of respiratory LTF on respiratory stability remains unclear.