Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons.

Cooling the caudal M ventrolateral medullary (VLM) surface for 30 s results in a sustained apnea in anesthetized goats but only a 30% decrease in breathing in awake goats. The purpose of the present study was to determine, in the awake state, the effect of prolonged (minutes, hours) caudal M neuronal dysfunction on eupneic breathing and CO2 sensitivity. Dysfunction was created by ejecting excitatory amino acid receptor antagonists or a neurotoxin on the VLM surface through guide tubes chronically implanted bilaterally on a 10- to 12-mm2 portion of the caudal M VLM surface of 12 goats. Unilateral and bilateral ejections (1 microliter) of selective antagonists for N-methyl-D-aspartic acid or non-N-methyl-D-aspartic acid receptors had no significant effect on eupneic breathing or CO2 sensitivity. Unilateral ejection of a nonselective excitatory amino acid receptor antagonist generally had no effect on eupneic breathing or CO2 sensitivity. However, bilateral ejection of this antagonist resulted in a significant 2-Torr hypoventilation during eupnea and a significant reduction in CO2 sensitivity to 60 +/- 9% of control. Unilateral ejection of the neurotoxin kainic acid initially stimulated breathing; however, breathing then returned to near control with no incidence of apnea. After the kainic acid ejection, CO2 sensitivity was reduced significantly to 60 +/- 7% of control. We conclude that in the awake state a prolonged dysfunction of caudal M VLM neurons results in compensation by other mechanisms (e.g., carotid chemoreceptors, wakefulness) to maintain near-normal eupneic breathing, but compensation is more limited for maintaining CO2 sensitivity.

Effects of cooling the ventrolateral medulla on diaphragm activity during NREM sleep.

Dysfunction through cooling of neurons near the ventrolateral medullary (VLM) surface results in apnea in the anesthetized state, whereas similar neuronal dysfunction in the awake state only modestly decreases breathing. The purpose of this study was to investigate effects on breathing, as measured by diaphragm electromyogram (EMGdi), of VLM neuronal dysfunction during NREM sleep, a naturally occurring change in state. In six goats, thermodes for cooling were chronically implanted between the first hypoglossal rootlet and the pontomedullary junction (area M and area S). During wakefulness and NREM sleep, bilateral VLM cooling (thermode temp = 20 degrees C) for 30 sec decreased EMGdi mean activity and minute EMGdi (p < 0.05) and lengthened the time between diaphragm contractions. During NREM sleep, reductions in mean and minute EMGdi during cooling tended to be greater than during waking, but not significantly. However, following carotid body denervation. VLM cooling caused prolonged apnea during NREM sleep but only a brief apnea in the awake state. The data suggest that either intact VLM neuronal mechanisms or intact carotid afferents are necessary for sustained EMGdi activity during NREM sleep.