Phrenic Output Research Articles

Effect of thoracic deafferentation on load-compensating mechanisms in humans.

First-breath responses to graded elastic (delta E) and resistive (delta R) loads in 29 cervical cord-injured and 80 normal men were compared with those predicted assuming identical respiratory muscle pressure (Pmus) wave forms in the unloaded and loaded states. The cord-injured group's mean actual and predicted inspiratory duration (TI) responses were equal, indicating that the average duration of their phrenic discharge remained constant during both delta E and delta R. Their mean expiratory duration (TE) responses fell short of predictions with delta E but exceeded predictions with delta R, signifying that a neural mechanism hastened inspiration following delta E but postponed it following delta R. TE/(pred TE) values (an index of phrenic timing) from different loads were proportional to concomitant TI responses but not to indices of diaphragmatic force [peak Pmus, (VT/TI)/(pred VT/TI)], movement (VT, VT/TI), or duration of contraction [TI/(pred TI)]. These findings suggest that oropharyngeal and/or pulmonary receptors signaling airflow duration, rather than diaphragmatic length or tension receptors, adjust phrenic motoneuron timing during mechanical loading. The cord-injured group produced a normal tidal volume (VT) defense coupled with a depressed frequency (f) response to delta E and, conversely, a weak VT defense coupled with a normal f response to delta R. Since both groups' VT/TI responses surpassed predictions equally, the cord-injured group's deficit was attributable entirely to impaired regulation of TE during delta E and TI during delta R. Thus chest wall receptors modulate duration and timing, but probably not average intensity, of the phrenic output during loading. Nearly one-third of the normal, but virtually none of the cord-injured, samples prolonged TI against large delta R and shortened TI agaist large delta E, suggesting that thoracic deafferentation impairs human ability to distinguish large delta R from delta E. These latter findings support the hypothesis that chest wall afferents subserve perception of respiratory force or position in humans.

Augmentation of carotid body chemoreceptor responses by isoproterenol in the cat

The effects of intravenous injections of isoproterenol (0.5–2 μg) on the response of carotid body chemoreceptor afferents and on integrated phrenic activity were investigated in twelse anesgthetized and three decerebrate, unanesthetized cats. All animals were paralyzed and artificially ventilated. Isoproterenol stimulated carotid chemoreceptor activity and this stimulation was augmented by both hypoxia and hypercapnia. Following an injection of isoproterenol, the ratio of the minute phrenic activity relative to mean carotid chemoreceptor activity was increased. Thus, the stimulation of inspiratory phrenic output exceeded the stimulation of the chemoreceptor afferent inout, and the peripheral chemoreflex activity does not account for the entire ventilatory response. To distinguish between a direct effect of isoproterenol and a possible secondary effect mediated via an increased venous return and an increased Pa CO 2 , the latencies of the response of carotid chemoreceptors to both isoproterenol and hypercapnia were compared before and after carbonic anhydrase inhibition by acetazolamide. After acetazolamide, the latency of the response to hypercapnia increased ferom 3.5 sec to 8 sec whereas the latency of response to isoproterenol increased less, from 4.7 sec to 6.3 sec. Thus, isoproterenol stimulation was not mediated by CO 2H +. Propanolol, which blocked the systemic vascular effect, only partially blocked the chemoreceptor stimulation caused by isoproterenol, indicting that the effect of isoproterenol on chemoreceptor activity was not due to systemic cardiovascular changes.

Augmentation of phrenic neural activity by increased rates of lung inflation.

Studies were conducted in anesthetized paralyzed dogs using a cycle-triggered constant-flow ventilator, which ventilated the animal in phase with the recorded phrenic neural activity. Intermittently tests were performed in which the animal was ventilated with a different airflow for a single breath. Increased airflows, within the range generated during spontaneous breathing, caused an increased rate of rise of the moving average phrenic neurogram and a shortening of the duration of the nerve burst. The magnitude of the increase in the rate of rise of the neurogram was related to the level of inspiratory airflow. Tests with brief pulses of airflow showed that an increase in the rate of rise of the phrenic neurogram could be produced without inflating the lung above the resting tidal volume of the animal. Similar results were obtained with negative-pressure ventilation and the effects were abolished by vagotomy. This vagally mediated augmentation of phrenic neural output may accelerate the inspiratory volume change in the lung during spontaneous breathing at hyperpneic levels.

Changes in the respiratory pattern induced by halothane in the cat.

The effect of halothane on the respiratory pattern was investigated in lightly anaesthetized cats. Following the administration of 2.0% halothane there was a transient increase in respiratory frequency because of a decrease in the duration of expiration, followed by a progressive decrease in respiratory frequency as a result of prolongation of inspiration; both events could be demonstrated before and after vagotomy. During the steady state obtained following the administration of 0.5, 1.0 and 1.5% halothane and after vagotomy there was a decrease in the duration of expiration and a progressive increase in the duration of inspiration. Tidal phrenic output decreased progressively as the concentration of halothane was increased. These results suggest that changes in respiratory pattern seen during halothane anaesthesia might involve some excitatory central mechanisms other than the bulbopontine system.

Effects of lesions in the parabrachial nucleus on the mechanisms for central and reflex termination of inspiration in the cat.

The effects of PCO2 and body temperature on the time course and peak amplitude of the central inspiratory activity (CIA) and the inspiratory "off-switch" threshold was studied in apneustic and non-apneustic cats. Apneusis resulted from lesions of the inspiratory inhibiting structures of the medial parabrachial nucleus (NPBM) and by interrupting vagal volume feedback. The cats were paralyzed and ventilated either proportionally to their phrenic output or at predetermined rate and volume. The dependence of the rate of rise and maximal amplitude of phrenic activity on PCO2 and body temperature were comparable in apneustic and non-lesioned animals. The Hering-Breuer volume threshold for inspiratory termination was increased following the rostral pontine lesions. Both hyperthermia and hypercapnia caused augmentation of the absolute rate of rise of inspiratory activity but hypercapnia, in contrast to hyperthermia, caused virtually no change in the fractional increment per unit time. With hypercapnia the inspiratory "off-switch" threshold was raised in the apneustic animals in intact ones, whereas hyperthermia did not seem to influence this threshold. In apneustic conditions expiratory duration remained constant, independent of the large variations in the inspiratory durations. Our results suggest that the NPBM merely provides an excitatory, threshold-lowering input to the inspiratory "off-switch" mechanism.

Relationship between phrenic nerve activity and ventilation.

Relationship between phrenic nerve activity and ventilation.