Large lesions in the pre-Botzinger complex area eliminate eupneic respiratory rhythm in awake goats

• Published in: Journal of applied physiology (1985) Vol. 97; no. 5; pp. 1629 - 1636
• Main Authors: Wenninger, J. M, Pan, L. G, Klum, L, Leekley, T, Bastastic, J, Hodges, M. R, Feroah, T. R, Davis, S, Forster, H. V
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01-11-2004; American Physiological Society
• Subjects: Animals; Biological and medical sciences; Diaphragm - physiology; Female; Fundamental and applied biological sciences. Psychology; Goats; Ibotenic Acid; Inhalation; Male; Medulla Oblongata - physiology; Medulla Oblongata - physiopathology; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Periodicity; Respiration; Respiration Disorders - chemically induced; Respiration Disorders - physiopathology; Respiratory Muscles - physiology; Respiratory system; Vertebrates: nervous system and sense organs; Wakefulness; Breathing rate; NK1 Tachykinin receptor; Brain stem; Central nervous system; Gene expression; Encephalon; Vertebrata; Mammalia; Neuron; Goat; terminal apnea; Artiodactyla; Lesion; Respiration; Respiratory control; respiratory rhythm generator; Ungulata; inspiratory and preinspiratory neurons
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00953.2003

Department of Physiology and Pediatrics, Medical College of Wisconsin, Zablocki Veterans Affairs Medical Center, and Department of Physical Therapy, Marquette University, Milwaukee, Wisconsin 53226
Submitted 4 September 2003
; accepted in final form 2 June 2004
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 µl, 50 mM) injection into the pre-BötzC area resulted in a tachypneic hyperpnea that reached a maximum (132 ± 10.1 breaths/min) 30–90 min after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (arterial P O 2 40 Torr) and hypercapnia (arterial P CO 2 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 ( 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.
respiratory rhythm generator; terminal apnea; inspiratory and preinspiratory neurons
Address for reprint requests and other correspondence: H. V. Forster, Dept. of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226 (E-mail: bforster{at}mcw.edu ).