Phasic vagal influence on inspiratory motor output in anesthetized human subjects

Abstract

Vagal influence on inspiratory motor output was assessed in 20 normal subjects and in 12 patients with respiratory disorders under enflurane anethesia using the method of airway occlusion. The change in inspiratory duration during occlusion (delta TI) was measured from mechanical parameters (respiratory flow and tracheal pressure). In eight of the subjects, however, the effect of occlusion and augmentation of tidal volume was further evaluated from diaphragmatic electromyogram. In normal subjects delta TI (mechanical) averaged 0.15 s (range -0.1 to +0.77 s) and correlated with the duration of inspiration during occlusion. Electromyographic observations indicated that the change in neural TI exceeds the change in mechanical TI by approximately 0.2 s and that augmentation of tidal volume shortens TI with no apparent volume threshold. There was a tendency for vagal influence to be higher with restrictive lung disease and lower with obstructive airway disease. These observations indicate that a majority of humans display a significant vagal influence on TI in the spontaneous tidal volume range under anesthesia.

Effects of inspiratory flow on diaphragmatic motor output in normal subjects

“…A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32). Our laboratory has recently demonstrated a marked effect of inspiratory V on TI n in normal, awake subjects over the V range of 0.8-2.5 l/s (11).…”

“…There is no information in humans regarding the possible excitatory effect of V (see 2 above). A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32).…”

Effects of inspiratory flow on diaphragmatic motor output in normal subjects

“…A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32). Our laboratory has recently demonstrated a marked effect of inspiratory V on TI n in normal, awake subjects over the V range of 0.8-2.5 l/s (11).…”

“…There is no information in humans regarding the possible excitatory effect of V (see 2 above). A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32).…”

Use‐dependent learning and memory of the Hering–Breuer inflation reflex in rats

“…Another interesting question is whether patients with chronic elevation or depression of lung volume due to increases or decreases in lung compliance demonstrate abnormal HBIR or phasic volume‐related feedback compared with healthy subjects. Previous studies have shown that phasic modulations of t I and t E are attenuated in patients with increased lung compliance (as in chronic obstructive pulmonary disease) and augmented in those with decreased lung compliance (as in restrictive lung disease; Polacheck et al 1980; Gautier et al 1981; Tryfon et al 2001). It has been hypothesized that a possible mechanism for such disease‐dependent effects is central adaptation to continued volume‐related afferent traffic (van Lunteren, 2001).…”

“…However, human subjects do exhibit normal SAR discharge during eupnoeic breathing (Guz & Trenchard, 1971). Studies have shown that abrupt airway occlusion at end‐inspiration prolongs t E (Gautier et al 1981; Tryfon et al 2001), whereas occlusion at end‐expiration shortens t I (Polacheck et al 1980), indicating significant phasic volume‐related feedback modulation of the eupnoeic rhythm in humans. Similar phasic modulations of t I and t E have also been demonstrated in awake subjects during the first breath of assisted ventilation or PEEP before significant changes in chemical drive or conscious perception begin to develop (BuSha et al 2002; Haberthur & Guttmann, 2005).…”

Exertional dyspnoea in patients with mild‐to‐severe chronic obstructive pulmonary disease: neuromechanical mechanisms

“…In this context there is indirect evidence from past studies that afferent feedback from the overloaded and weakened inspiratory muscles in COPD is important in the genesis of increased IND and exertional dyspnoea (Langer et al., 2018; O'Donnell et al., 2006). The putative role of inhibitory SAPSRs inputs in conveying information about change in V T (or lack thereof) in response to increasing IND during exercise in chronically hyperinflated patients with destructive emphysema remains unclear (Dallak et al., 2007; Polacheck et al., 1980).…”

Effects of inspiratory flow on diaphragmatic motor output in normal subjects

“…A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32). Our laboratory has recently demonstrated a marked effect of inspiratory V on TI n in normal, awake subjects over the V range of 0.8-2.5 l/s (11).…”

“…There is no information in humans regarding the possible excitatory effect of V (see 2 above). A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32).…”

Use‐dependent learning and memory of the Hering–Breuer inflation reflex in rats

“…Another interesting question is whether patients with chronic elevation or depression of lung volume due to increases or decreases in lung compliance demonstrate abnormal HBIR or phasic volume‐related feedback compared with healthy subjects. Previous studies have shown that phasic modulations of t I and t E are attenuated in patients with increased lung compliance (as in chronic obstructive pulmonary disease) and augmented in those with decreased lung compliance (as in restrictive lung disease; Polacheck et al 1980; Gautier et al 1981; Tryfon et al 2001). It has been hypothesized that a possible mechanism for such disease‐dependent effects is central adaptation to continued volume‐related afferent traffic (van Lunteren, 2001).…”

“…However, human subjects do exhibit normal SAR discharge during eupnoeic breathing (Guz & Trenchard, 1971). Studies have shown that abrupt airway occlusion at end‐inspiration prolongs t E (Gautier et al 1981; Tryfon et al 2001), whereas occlusion at end‐expiration shortens t I (Polacheck et al 1980), indicating significant phasic volume‐related feedback modulation of the eupnoeic rhythm in humans. Similar phasic modulations of t I and t E have also been demonstrated in awake subjects during the first breath of assisted ventilation or PEEP before significant changes in chemical drive or conscious perception begin to develop (BuSha et al 2002; Haberthur & Guttmann, 2005).…”

Exertional dyspnoea in patients with mild‐to‐severe chronic obstructive pulmonary disease: neuromechanical mechanisms

“…In this context there is indirect evidence from past studies that afferent feedback from the overloaded and weakened inspiratory muscles in COPD is important in the genesis of increased IND and exertional dyspnoea (Langer et al., 2018; O'Donnell et al., 2006). The putative role of inhibitory SAPSRs inputs in conveying information about change in V T (or lack thereof) in response to increasing IND during exercise in chronically hyperinflated patients with destructive emphysema remains unclear (Dallak et al., 2007; Polacheck et al., 1980).…”

Effects of inspiratory flow on diaphragmatic motor output in normal subjects

“…A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32). Our laboratory has recently demonstrated a marked effect of inspiratory V on TI n in normal, awake subjects over the V range of 0.8-2.5 l/s (11).…”

“…There is no information in humans regarding the possible excitatory effect of V (see 2 above). A small effect of V on TI n (1 above) was found in several human studies (20,22,29,32). However, the range of V exam-ined was very small [essentially between zero (occlusion) and resting V (ϳ0.3-0.5 l/s)], and the subjects were anesthetized (29) or asleep (20,22,32).…”

Use‐dependent learning and memory of the Hering–Breuer inflation reflex in rats

“…Another interesting question is whether patients with chronic elevation or depression of lung volume due to increases or decreases in lung compliance demonstrate abnormal HBIR or phasic volume‐related feedback compared with healthy subjects. Previous studies have shown that phasic modulations of t I and t E are attenuated in patients with increased lung compliance (as in chronic obstructive pulmonary disease) and augmented in those with decreased lung compliance (as in restrictive lung disease; Polacheck et al 1980; Gautier et al 1981; Tryfon et al 2001). It has been hypothesized that a possible mechanism for such disease‐dependent effects is central adaptation to continued volume‐related afferent traffic (van Lunteren, 2001).…”

“…However, human subjects do exhibit normal SAR discharge during eupnoeic breathing (Guz & Trenchard, 1971). Studies have shown that abrupt airway occlusion at end‐inspiration prolongs t E (Gautier et al 1981; Tryfon et al 2001), whereas occlusion at end‐expiration shortens t I (Polacheck et al 1980), indicating significant phasic volume‐related feedback modulation of the eupnoeic rhythm in humans. Similar phasic modulations of t I and t E have also been demonstrated in awake subjects during the first breath of assisted ventilation or PEEP before significant changes in chemical drive or conscious perception begin to develop (BuSha et al 2002; Haberthur & Guttmann, 2005).…”

Exertional dyspnoea in patients with mild‐to‐severe chronic obstructive pulmonary disease: neuromechanical mechanisms

“…In this context there is indirect evidence from past studies that afferent feedback from the overloaded and weakened inspiratory muscles in COPD is important in the genesis of increased IND and exertional dyspnoea (Langer et al., 2018; O'Donnell et al., 2006). The putative role of inhibitory SAPSRs inputs in conveying information about change in V T (or lack thereof) in response to increasing IND during exercise in chronically hyperinflated patients with destructive emphysema remains unclear (Dallak et al., 2007; Polacheck et al., 1980).…”