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1 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
2 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Physical Therapy, Marquette University
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
4 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Physiology, Zablocki VA Medical Center, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: bforster{at}mcw.edu.
In awake goats, 29% bilateral destruction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-Botzinger Complex (pre-BotzC) area with saporin conjugated to substance P (SP-SAP) results in transient disruptions of the normal pattern of eupneic respiratory muscle activation (26). Therefore, the purpose of these studies was to determine whether large or total lesioning in the pre-BotzC area of goats would eliminate phasic diaphragm activity and the eupneic breathing pattern. In awake goats that already had 29% bilateral destruction of NK1R-expressing neurons in the pre-BotzC area, bilateral ibotenic acid (IA, 10µl, 50mM) injection into the pre-BotzC area resulted in a tachypneic hyperpnea that reached a maximum (132±10.1 brs/min) about 30 to 90 minutes after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (PaO2 ~40mmHg) and hypercapnia (PaCO2 ~60mmHg), and 11±3 minutes after the peak tachypnea, respiratory failure was followed by cardiac arrest in 3 airway-intact goats. However, after the peak tachypnea in 4 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 (~90s), 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-BotzC area were lesioned in these goats. We conclude that in the awake state, the pre-BotzC is critical for generating a diaphragm, eupneic respiratory rhythm, and that in the absence of the pre-BotzC, spontaneous breathing reflects the activity of an expiratory rhythm generator.
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