Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

Abstract

Sandhu MS, Lee KZ, Fregosi RF, Fuller DD. Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats. J Appl Physiol 109: 279 -287, 2010. First published April 15, 2010 doi:10.1152/japplphysiol.01422.2009 can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be an important determinant of phrenic LTF. Here we test the hypothesis that acute PhrX influences immediate and long-term phrenic motor responses to hypoxia. Phrenic neurograms were recorded in anesthetized, ventilated, and vagotomized adult male rats with intact phrenic nerves or bilateral PhrX. Data were obtained before (i.e., baseline), during, and after three 5-min bouts of isocapnic hypoxia. Inspiratory burst amplitude during hypoxia (%baseline) was greater in PhrX than in phrenic nerve-intact rats (P Ͻ 0.001). Similarly, burst amplitude 55 min after IH was greater in PhrX than in phrenic nerve-intact rats (175 Ϯ 9 vs. 126 Ϯ 8% baseline, P Ͻ 0.001).In separate experiments, phrenic bursting was recorded before and after PhrX in the same animal. Afferent bursting that was clearly observable in phase with lung deflation was immediately abolished by PhrX. The PhrX procedure also induced a form of facilitation as inspiratory burst amplitude was increased at 30 min post-PhrX (P ϭ 0.01 vs. pre-PhrX). We conclude that, after PhrX, axotomy of phrenic motoneurons and, possibly, removal of phrenic afferents result in increased phrenic motoneuron excitability and enhanced LTF following IH. axotomy; phrenic motoneurons; plasticity EXPOSURE TO INTERMITTENT HYPOXIA (IH) over short periods (e.g., minutes to hours) can evoke a persistent increase in respiratory motor output, termed long-term facilitation (LTF) (35,48,50). LTF has been observed in awake (26, 35) and sleeping humans (53) and in a wide range of animal species (22,46,48). The mechanisms underlying LTF have been studied extensively over the last 10 -15 years, primarily in anesthetized animals (reviewed in Refs. 42,49,50). In anesthetized animals, LTF is typically manifest as an increase in the inspiratory burst amplitude of phrenic (19) and/or hypoglossal (XII) extracellular nerve recordings (20). Recordings of in vivo (19) and in vitro (10) respiratory motor LTF are typically made from cut respiratory muscle nerves. More specifically, the phrenic and/or XII nerves are cut, and subsequent extracellular recordings are made from the central end of the nerve. This procedure can provide stability to the neurophysiological recording procedures, particularly when a dorsal surgical approach is used, but also has the potential to alter respiratory motor output and...

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

“…However, this absence was likely due to uncontrolled CO 2 which was decreased in all of the aforementioned studies. In support of this, PA has been observed in most studies in which isocapnia was maintained (141, 214, 232, 345, 346, 348, 398). …”

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

“…A final comment is warranted regarding postural impacts on diaphragm function. Similar to prior reports (9,14,15,17,41), rats were studied in the supine position to provide suitable access to the trachea and phrenic nerves. Studies in humans have clearly demonstrated that posture can impact diaphragm function.…”

“…Axotomy can trigger neuronal depolarization (33) and increases in phrenic nerve activity (42). However, axotomy effects should be limited to ipsilateral phrenic motoneurons with limited, if any, impact on contralateral motor pools.…”

“…These procedures were adapted from our prior publications (9,14,17,29,41). Isoflurane anesthesia (3-4% in O 2) was induced in a closed chamber followed by intraperitoneal injection of urethane (1.6 g/kg; Sigma, St. Louis, MO).…”

“…Another PE-50 catheter was placed in the femoral artery and connected to a pressure transducer (Statham P-10EZ pressure transducer; amplifier CP122 AC/DC strain gauge amplifier; Grass Instruments, West Warwick, RI) for arterial pressure and blood gas measurements. The ipsilateral phrenic nerve was isolated in the cervical region via a ventral approach (32,40,41). The exposed nerve was covered in mineral oil but not manipulated at this time.…”