Experimental protocols and preparations to study respiratory long term facilitation

Abstract

Respiratory long-term facilitation is a form of neuronal plasticity that is induced following exposure to intermittent hypoxia. Long-term facilitation is characterized by a progressive increase in respiratory motor output during normoxic periods that separate hypoxic episodes and by a sustained elevation in respiratory activity for up to 90 min after exposure to intermittent hypoxia. This phenomenon is associated with increases in phrenic, hypoglossal or carotid sinus nerve inspiratory-modulated discharge. The examination of long-term facilitation has been steadily ongoing for approximately 3 decades. During this period of time a variety of animal models (e.g. cats, rats and humans), experimental preparations and intermittent hypoxia protocols have been used to study long-term facilitation. This review is designed to summarize the strengths and weaknesses of the models, preparations and protocols that have been used to study LTF over the past 30 years. The review is divided into two primary sections. Initially, the models and protocols used to study LTF in animals other than humans will be discussed, followed by a section specifically focused on human studies. Each section will begin with a discussion of various factors that must be considered when selecting an experimental preparation and intermittent hypoxia protocol to examine LTF. Model and protocol design recommendations will follow, with the goal of presenting a prevailing model and protocol that will ultimately ensure standardized comparisons across studies.

Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons

“…Rodents exposed to intermittent hypoxia are most commonly used to study distinct mechanisms unique to OSA (8,26,29). Intermittent hypoxia effects in rodents importantly help understand OSA pathogenesis, but translation of the results to humans is difficult because of uncertainty regarding the quantitative relationships between different intermittent hypoxia protocols in rodents and OSA severity in humans, as well as any qualitative and/or quantitative differences in the neurochemical control of the upper airway and breathing in humans vs. rodents (for reviews see Refs.…”

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

“…There is considerable heterogeneity in the magnitude and duration of LTF between species depending upon the exact hypoxic induction protocol utilized; the effects of various protocols between species have recently been expertly reviewed (234, 257, 274). Ventilatory LTF is difficult to study experimentally and appears to depend on sleep-wakefulness state, species, and the hypoxic induction protocol; this topic has also been reviewed recently (234).…”

“…Ventilatory LTF is difficult to study experimentally and appears to depend on sleep-wakefulness state, species, and the hypoxic induction protocol; this topic has also been reviewed recently (234). Most of the experimental work defining molecular mechanisms of LTF has been done in anesthetized animal preparations (primarily in rat) and focuses on phrenic LTF.…”

Repetitive acute intermittent hypoxia increases expression of proteins associated with plasticity in the phrenic motor nucleus

“…For example, acute intermittent hypoxia (AIH; 3 hypoxic episodes) elicits a form of respiratory plasticity known as phrenic long-term facilitation (pLTF; Bach and Mitchell, 1996; Matieka and Sandhu, 2011; Mitchell and Terada, 2011; Mitchell et al, 2001). Our understanding of cellular mechanisms underlying AIH-induced pLTF has advanced considerably in recent years (Dale-Nagle et al, 2010; Feldman et al, 2003; MacFarlane et al, 2009; Mahamed and Mitchell, 2007; Mitchell et al, 2001).…”