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Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats. J Appl Physiol (1985) 2004 Nov;97(5):1629-36

Date

07/13/2004

Pubmed ID

15247161

DOI

10.1152/japplphysiol.00953.2003

Scopus ID

2-s2.0-7044227823 (requires institutional sign-in at Scopus site)   80 Citations

Abstract

In awake goats, 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-Bötzinger complex (pre-BötzC) area with saporin conjugated to substance P results in transient disruptions of the normal pattern of eupneic respiratory muscle activation (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, and Forster HV. J Appl Physiol 97: 1620-1628, 2004). Therefore, the purpose of these studies was to determine whether large or total lesioning in the pre-BötzC area of goats would eliminate phasic diaphragm activity and the eupneic breathing pattern. In awake goats that already had 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-BötzC area, bilateral ibotenic acid (10 microl, 50 mM) injection into the pre-BötzC area resulted in a tachypneic hyperpnea that reached a maximum (132 +/- 10.1 breaths/min) approximately 30-90 min after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (arterial Po2 approximately 40 Torr) and hypercapnia (arterial Pco2 approximately 60 Torr), and, 11 +/- 3 min after the peak tachypnea, respiratory failure was followed by cardiac arrest in three airway-intact goats. However, after the peak tachypnea in four tracheostomized goats, mechanical ventilation was initiated to maintain arterial blood gases at control levels, during which there was no phasic diaphragm or abdominal muscle activity. When briefly removed from the ventilator (approximately 90 s), these goats became hypoxemic and hypercapnic. During this time, minimal, passive inspiratory flow resulted from phasic abdominal muscle activity. We estimate that 70% of the neurons within the pre-BötzC area were lesioned in these goats. We conclude that, in the awake state, the pre-BötzC is critical for generating a diaphragm, eupneic respiratory rhythm, and that, in the absence of the pre-BötzC, spontaneous breathing reflects the activity of an expiratory rhythm generator.

Author List

Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV

Authors

Hubert V. Forster PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Diaphragm
Female
Goats
Ibotenic Acid
Inhalation
Male
Medulla Oblongata
Periodicity
Respiration
Respiration Disorders
Respiratory Muscles
Wakefulness