Differential alteration by hypercapnia and hypoxia of the apneustic respiratory pattern in decerebrate cats.

1. A combination of bilateral lesions within the nucleus parabrachialis medialis complex (n.p.b.m.) and bilateral vagotomy typically resulted in an apneustic respiratory pattern in decerebrate and paralysed cats. Integrated efferent phrenic nerve activity was recorded as an index of the respiratory rhythm.2. Changes in components of this apneustic breathing cycle were evaluated in response to steady-state hypercapnia and hypoxia. The components evaluated were (a) the period of phrenic discharge (inspiratory time, T(I)), (b) the period of no detectable phrenic activity (expiratory time, T(E)), (c) the total duration of the apneustic respiratory cycle (T(TOT), the sum of T(I) and T(E)), and (d) the average height of the integrated phrenic nerve activity (apneustic depth).3. Elevations of P(A, CO2) from values below 45 torr to 50-60 torr, under both hyperoxic and normoxic conditions, resulted in significant elevations of T(I), T(E), T(TOT) and depth. Further P(A, CO2) elevations to approximately 70 torr caused no change, or frequently, a decrease in T(I), T(E) and T(TOT); the apneustic depth increased in most animals.4. Diminutions in P(A, O2) from normoxic to hypoxic levels at isocapnia typically caused an increase in apneustic depth and, concomitantly, significant decreases in T(I), T(E) and T(TOT).5. Pharmacological stimulation of the carotid chemoreceptors by intracarotid administration of 1.0-20 mug NaCN produced a premature onset of phrenic nerve activity if delivered during the expiratory period. Such NaCN administrations, delivered during the inspiratory phase, resulted in an augmentation of the integrated phrenic discharge and a premature termination of phrenic activity. Carotid sinus nerve section eliminated the response to NaCN administration.6. In experimental animals having bilateral carotid sinus nerve section, normoxic hypercapnia caused similar changes in the apneustic breathing pattern to those recorded in cats having intact carotid chemoreceptors. However, isocapnic hypoxia induced time-dependent changes in the pattern of phrenic discharge including diminutions in depth, an onset of gasping-type activity, or expiratory apnea.7. In a few animals, bilateral n.p.b.m. lesions and bilateral vagotomy resulted in expiratory apnea which was continuous as long as ventilation with air was maintained. This expiratory apnea was replaced by an apneustic breathing pattern following diminutions of P(A, O2) below 90 torr. This establishment of an apneustic breathing pattern by hypoxia was observed both in animals having intact, as well as sectioned, carotid sinus nerves. This expiratory apnea could also be terminated by a single apneustic inspiration following general somatic stimulation or, in cats having intact carotid chemoreceptors, following intracarotid NaCN administration.8. It is concluded that hypercapnia and hypoxia produce differential alterations of the apneustic breathing pattern in decerebrate cats. Further, the hypoxia-induced changes are considered to represent the net result of carotid chemoreceptor stimulation and brain stem depression. The results of this study are considered in the context of proposed mechanisms for phase-switching of the respiratory cycle.