CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.     

Modulation of respiratory responses to carotid sinus nerve stimulation by brain hypoxia.

This study examines the effect of progressive isocapnic CO hypoxemia on respiratory afterdischarge and the phrenic neurogram response to supramaximal carotid sinus nerve (CSN) stimulation. Twelve anesthetized, vagotomized, peripherally chemodenervated, ventilated cats with blood pressure controlled were studied. During isocapnic hypoxemia, the amplitude of the phrenic neurogram was progressively depressed. In contrast, the increase in peak phrenic amplitude produced by CSN stimulation was unchanged, suggesting that the central respiratory response to CSN stimulation is unaffected by progressive hypoxemia. The time constant of respiratory afterdischarge (tau) was calculated from best-fit plots of phrenic amplitude vs. time after cessation of CSN stimulation. Under control conditions the value of tau was 57.7 +/- 3 (SE) s (n = 12). During progressive isocapnic hypoxemia, tau decreased as a linear function of arterial O2 content (CaO2) such that a 40% reduction of CaO2 resulted in a 48% reduction in tau. This reduction of respiratory afterdischarge may contribute to the genesis of periodic breathing during hypoxia.     

Cervical sympathetic and phrenic nerve responses to progressive brain hypoxia

To determine if depression of central respiratory output during progressive brain hypoxia (PBH) can be generalized to other brain stem outputs, we examined the effect of PBH on the tonic (tSCS) and inspiratory-synchronous (iSCS) components of preganglionic superior cervical sympathetic (SCS) nerve activity. Peak phrenic and SCS activity were measured in nine anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats. PBH was produced by inhalation of 0.5% CO in 40% O2 while blood pressure and end-tidal CO2 were maintained constant. A progressive reduction in arterial O2 content from 14.3 +/- 0.6 to 4.5 +/- 0.3 vol% caused a 79 +/- 7% depression of peak phrenic activity and an 84 +/- 10% reduction of iSCS activity, but tSCS activity increased 42 +/- 21%. During CO2 rebreathing, iSCS activity increased in parallel with peak phrenic activity while tSCS activity was unchanged. The slopes of the CO2 responses of both phrenic (6.3 +/- 1.2%max/mmHg) and iSCS (4.6 +/- 0.8%max/mmHg) activity were unaffected by PBH. In four of nine hypocapnic and three of nine hypoxic studies, inspiratory activity in the SCS nerve was observed even after completely silencing the phrenic neurogram.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extracellular potassium homeostasis in the cat medulla during progressive brain hypoxia

Brain extracellular potassium [( K+]ec) in the ventral respiratory group of the medulla and the phrenic neurogram were recorded in anesthetized vagotomized peripherally chemodenervated ventilated cats during progressive isocapnic carbon monoxide (CO) hypoxia. During hypoxia, the phrenic neurogram was progressively depressed and became silent when arterial O2 content (CaO2) was reduced by 62 +/- 3% (SE). Gasping was seen in the phrenic neurogram when CaO2 was reduced by 78 +/- 1%. Medullary [K+]ec, an indicator of energy production failure due to O2 insufficiency, was 3.2 +/- 0.4 mM before hypoxia and was statistically unchanged at the onset of phrenic apnea during CO hypoxia (4 +/- 0.7 mM). By the onset of gasping, [K+]ec had increased to 6.1 +/- 1 mM, a value that tended to be different from control (P less than 0.1). After initiation of gasping, the rate of rise of [K+]ec increased, and [K+]ec reached a maximum value of 14.3 +/- 2.7 mM before hypoxia was terminated. With reoxygenation, [K+]ec returned to control levels within 20 min. On the basis of these results, we have drawn two major conclusions. 1) Hypoxic depression to the point of phrenic apnea does not appear to be caused by medullary energy insufficiency as measured by loss of [K+]ec homeostasis. 2) The rapid rise in [K+]ec in the medulla that characterizes severe hypoxia is closely associated with the onset of gasping in the phrenic neurogram, suggesting that gasping may serve as a marker for loss of medullary ionic homeostasis and thus onset of medullary energy insufficiency during hypoxia.     

Enflurane depresses activity of the medullary inspiratory neurons in the cat

The effect of enflurane on the firing activity (spikes/sec) of the inspiratory neurons of the dorsal respiratory group (DRG) of the medulla oblongata was studied in decerebrate, paralyzed, mechanically ventilated cats before and after bilateral cervical vagotomy. Inspiratory neuronal activity, phrenic neurogram, arterial blood pressure, tracheal pressure, and end tidal CO2 concentration were recorded. Cells whose firing activity was in phase with that of the phrenic nerve were considered inspiratory neurons. Administration of 1 and 2% enflurane in oxygen produced gradual, significant, and dose-dependent depression of the cell activity with cervical vagi either intact or severed. Recovery of the cell activity occurred after termination of enflurane administration. In cats with intact vagi, 10 min after introduction of 1 and 2% enflurane, the cell activity (mean +/- SE) expressed as percentage of the control was 70 +/- 6% (P less than 0.05) and 48 +/- 5% (P less than 0.01), respectively. Bilateral cervical vagotomy did not affect the degree of cell depression due to enflurane. Hypercarbia induced by inhalation of 5% CO2 increased cell activity, but it did not block enflurane-induced cell depression, although it reduced it. It may be concluded that enflurane depresses the activity of the inspiratory neurons of the DRG. The results also suggest that the respiratory depressant effect of enflurane has a central component and that the DRG region may serve as a site to mediate the enflurane-induced respiratory depression.     

Augmentation of hypoxic respiration after brief hyperoxia in the anesthetized cat: Putative function of GABA<Subscript>A</Subscript> neurotransmission

In this study, we attempted to determine the role of GABA neurotransmission in augmentation of hypoxic respiration by antecedent hyperoxic breathing. The experiments were performed in anesthetized, paralyzed and vagotomized cats divided into control and bicuculline (a GABA_A receptor blocker)-injected groups. The experimental protocol consisted of exposing the animals to successive hypoxic-hyperoxic-hypoxic conditions. Respiration was assessed using phrenic electroneurograms, from which the peak phrenic height, a surrogate of the tidal volume component, and respiratory rate were obtained, and their product, the respiratory minute output, was calculated. We found that prior hyperoxic ventilation increased the subsequent respiratory response to hypoxia by an average of 23.5%, compared with the preoxygen response. This increase was driven by volume respiration. The biphasic character of the hypoxic respiratory response, consisting of stimulatory and depressant phases, was sustained. Bicuculline abolished the augmentative effect on hypoxic respiration of prior hyperoxia, which suggests that oxygenation induces GABA_A-mediated hyperexcitability of respiratory neurons, possibly by the liberation of reactive oxygen species. We concluded that GABA neurotransmission is pertinent to the effect of hyperoxia on hypoxic respiratory reactivity.     

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing.

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents.     

Transient respiratory augmentation elicited by acute head-down tilt in the anesthetized cat

Acute head-downtilt (AHDT, 30°) in humans induces a transient ventilatoryaugmentation for 1-2 min accompanied by a high venous return.However, the mechanisms underlying this respiratory response remainobscure because of limitations of experiments carried out in humansubjects. The present study was undertaken to determine whetherAHDT-induced respiratory augmentation exists in the anesthetized,paralyzed, and ventilated cat and, if so, whether this response dependson 1) the cerebellum,2) the carotid sinus (CS)and/or vagal afferents, and3) elevation of central venousreturn. The integrated phrenic neurogram, arterial blood pressure,central venous pressure (CVP), and end-tidalPCO₂ were recorded before, during,and after AHDT. The results showed that AHDT produced a transient (~2min) enhancement of minute phrenic activity (~30%) primarily via anincrease in peak integrated phrenic neurogram amplitude associated witha remarkable elevation of CVP (~3 min). Cerebellectomy, CSdenervation, bilateral vagotomy, or clamping CVP did not affect thepresence of the AHDT-induced minute phrenic activity response. Thesefindings demonstrate that the anesthetized cat is a suitable model forinvestigating the mechanisms involved in AHDT-induced respiratoryaugmentation. Preliminary studies suggest that this response does notrequire the cerebellum, CS/vagal afferents, or an associated rise incentral venous return.

     

Central GABAergic mechanisms are involved in apnea induced by SLN stimulation in piglets.

Stimulation of the superior laryngeal nerve (SLN) results in apnea in animals of different species, the mechanism of which is not known. We studied the effect of the GABA(A) receptor blocker bicuculline, given intravenously and intracisternally, on apnea induced by SLN stimulation. Eighteen 5- to 10-day-old piglets were studied: bicuculline was administered intravenously to nine animals and intracisternally to nine animals. The animals were anesthetized and then decerebrated, vagotomized, ventilated, and paralyzed. The phrenic nerve responses to four levels of electrical SLN stimulation were measured before and after bicuculline. SLN stimulation caused a significant decrease in phrenic nerve amplitude, phrenic nerve frequency, minute phrenic activity, and inspiratory time (P < 0.01) that was proportional to the level of electrical stimulation. Increased levels of stimulation were more likely to induce apnea during stimulation that often persisted beyond cessation of the stimulus. Bicuculline, administered intravenously or intracisternally, decreased the SLN stimulation-induced decrease in phrenic nerve amplitude, minute phrenic activity, and phrenic nerve frequency (P < 0.05). Bicuculline also reduced SLN-induced apnea and duration of poststimulation apnea (P < 0.05). We conclude that centrally mediated GABAergic pathways are involved in laryngeal stimulation-induced apnea.     

Effect of withdrawal of respiratory CO2 oscillations on respiratory control at rest

We examined the effect of sudden withdrawal of respiratory oscillations of arterial PCO2 (CO2 oscillations) at resting metabolic rate on the control of respiration in 11 anesthetized paralyzed vagotomized dogs in normoxic normocapnia. A double-lumen endotracheal tube was inserted so that the left and right lungs were ventilated independently. By alternately ventilating each lung, we could completely abolish CO2 oscillations without affecting the mean blood gas levels (withdrawal of CO2 oscillations). The CO2 oscillation was calculated from arterial pH oscillation measured by a rapidly responding intra-arterial pH electrode. Respiratory center output was monitored by use of a moving time average of the phrenic neurogram. A 3-min period of withdrawal of CO2 oscillations was bracketed by two control periods (simultaneous ventilation of lungs for 3 min) to avoid the confounding effect of the baseline drift in the respiratory center output. The amplitude of the CO2 oscillations in the control was 2.33 +/- 0.89 (SD) Torr. When the difference in the mean level of arterial PCO2 between the control and withdrawal of CO2 oscillations was minimized (-0.09 +/- 0.54 Torr; P greater than 0.25), we found negligible change in the minute phrenic activity during withdrawal of CO2 oscillations (-0.02 +/- 6.11% of the control, P greater than 0.98, n = 49; 99% confidence interval -2.36 to 2.32%). Thus we conclude that the maintenance of normal respiration at rest is not critically dependent on a phasic afferent input to the respiratory center arising from respiratory CO2 oscillations.     

Biphasic ventilatory response of adult cats to sustained hypoxia has central origin

Hypoxia stimulates ventilation, but when it is sustained, a decrease in the response is often seen. The mechanism of this depression or "roll off" is unclear. In this study we attempted to localize the responsible mechanism at one of three possible sites: the carotid bodies, the central nervous system (CNS), or the ventilatory apparatus. The ventilatory response to sustained hypoxia (PETO2, 40-50 Torr) was tested in 5 awake and 14 anesthetized adult cats. The roll off was found in both anesthetized and awake cats. Isocapnic hypoxia initially increased ventilation as well as phrenic and carotid sinus nerve activity in anesthetized cats (288 +/- 31, 269 +/- 31, 273 +/- 29% of control value, respectively). During the roll off, ventilation and phrenic nerve activity decreased similarly (to 230 +/- 26 and 222 +/- 28%, respectively after the roll off), but in contrast carotid sinus nerve activity remained unchanged (270 +/- 26%). Thus the ventilatory roll off was reflected in phrenic but not in carotid sinus nerve activity. We conclude that the cat represents a useful animal model of the roll off phenomenon and that the mechanism responsible for the secondary decrease in ventilation lays within the CNS.     

Power spectra of inspiratory nerve activity with lung inflations in cats

To investigate the effect of lung inflations on the high-frequency synchrony (70-122 Hz) observed in the inspiratory activity of respiratory motor nerves of decerebrate cats, I applied a step increase in lung inflation pressure at fixed delays into the inspiratory phase and computed power spectra of phrenic neurograms before and during inflation. In 25 decerebrate paralyzed cats the frequency of the high spectral peak was 92.3 +/- 11.1 Hz before and 105.3 +/- 12.1 Hz during the step in inflation pressure, shifting upward by 13.0 +/- 6.0 Hz. For 8 of the 25 cats, the recurrent laryngeal and phrenic neurograms were recorded simultaneously. The high spectral peak was present during inspiration in the recurrent laryngeal power spectra and coherent with the high peak in the phrenic power spectra. In response to lung inflation, the high peak disappeared from the power spectra of the recurrent laryngeal nerve as the inspiratory activity was inhibited; a shift upward in frequency was not detectable. Comparing inspiratory times (TI, based on the phrenic neurograms) for breaths with no lung inflations to those for breaths with lung inflations, I found that lung inflations early in inspiration caused a decrease in TI, lung inflations at intermediates times had no effect on TI, and lung inflations late in inspiration caused an increase in TI. Despite lung inflation decreasing, not affecting, or increasing inspiratory duration and amplitude of the phrenic neurogram, lung inflation always caused a shift upward in the high-frequency peak of the phrenic power density. The fact that lung inflation, a powerful respiratory stimulus, affected the frequency of the high peak in a consistent manner suggests that the high-frequency synchrony is an important and robust feature of the central respiratory pattern generator.     

Effects of hypercapnia and hypoxia on abdominal expiratory nerve activity

We examined the effects of progressive hypercapnia and hypoxia on the efferent neural activity in a whole abdominal expiratory nerve (medial branch of the cranial iliohypogastric nerve (L1) in anesthetized, paralyzed dogs. To eliminate effects of phasic lung and chest-wall movements on expiratory activity, studies were performed in the absence of breathing movements. Progressive hyperoxic hypercapnia and isocapnic hypoxia were produced in the paralyzed animals by allowing 3-5 min of apnea to follow mechanical ventilation with 100% O2 or 35% O2 in N2, respectively; during hypoxia, isocapnia was maintained by intravenous infusion of tris(hydroxymethyl)aminomethane buffer at a predetermined rate. To quantify abdominal expiratory activity, mean abdominal nerve activity in a nerve burst was computed by integrating the abdominal neurogram and dividing by the duration of the nerve burst. Hypercapnia and hypoxia both increased mean abdominal nerve activity and decreased expiratory duration. In contrast to the ramplike phrenic neurogram, the abdominal neurogram consisted of three phases: an initial rising phase, a plateau phase in which abdominal nerve activity was approximately constant, and a terminal declining phase in which the activity returned to the base-line level. The height of this plateau phase and the rates of rise and decline of abdominal nerve activity all increased with increasing hypercapnia and hypoxia. We conclude that, with proprioceptive inputs constant, both hypercapnia and hypoxia are excitatory to abdominal expiratory neural activity.     

Changes of minute ventilation in rabbits in experimental hyperthermia

The relative effect of the temperature on respiratory rhythm generation was studied in muscle-relaxed, artificially ventilated and bilaterally vagotomized rabbits under general anaesthesia (urethane and chloralose). Hypercapnia was produced during normothermia (38.8 +/- 0.6 degrees C) and hyperthermia (40.5 +/- 0.3 degrees C). The basic physiological parameters, efferent phrenic nerve activity and gasometric determinations in arterial blood were recorded. In the animals ventilated with a classic respirator hyperthermia produced a 118% increase of Veq value with a simultaneous 28% rise of the partial pressure of CO2. An increase of the stroke volume of the respirator during hyperthermia (in a degree sufficient for achieving PaCO2 value equal to the control value during normothermia) produced a 2% fall of Veq value due to an 8% fall in amplitude of the respiratory movements without changes of respiratory rate. Breathing in of a hypercapnic mixture caused a 131% rise of Veq above the control value in normothermia. This rise was due both to the increased respiratory rate and respiratory amplitude. During ventilation by means of a respirator controlled by phrenic nerve activity hyperthermia increased the electrophysiological equivalent of minute ventilation by 34%, with a 109% rise in the respiratory rate and with no change in PaCO2. Breathing of a hypercapnic mixture increased Veq without inducing any statistically significant changes in the respiratory rate and amplitude. The analysis of the results suggests that the effect of raised temperature on respiratory rhythm generation is manifested mainly as an impairment of the respiratory amplitude. Maintaining of minute ventilation proportional to the magnitude of respiratory drive is decisive in this phenomenon.     

Ascorbyl palmitate augments hypoxic respiratory response in the cat

The redox signaling is germane for the hypoxia-sensing mechanisms at the carotid body. This raises the strong possibility that agents possess reducing and antioxidant attributes, such as ascorbate, could influence the hypoxic respiratory response. However, water solubility of ascorbate makes its effectiveness at membrane-associated target sites dubious. In this study, we sought to determine the effect of ascorbyl-6-palmitate (AP), a lipidsoluble derivative of ascorbate which penetrates biomembranes, on hypoxic respiration in the anesthetized, paralyzed and ventilated cat. AP was given by gavage: 600 mg/kg daily for 6 days before the beginning of the acute experiment. Respiration was then assessed from the phrenic electroneurogram, from which peak phrenic amplitude, a surrogate of tidal component, respiratory frequency, and their product, the minute phrenic output, were quantified. The response to normocapnic hypoxia, 7% O₂ in N₂, in the AP-treated cats was compared with that in controls. We found that AP augmented hypoxic respiration, delayed the appearance of hypoxic depression and decreased it, although the stimulatory/depressant character was preserved. The results suggest that the ascorbate moiety of AP interacts with the hypoxiasensing mechanisms. Ascorbate may affect hypoxic respiration at multiple stages of chemotransduction pathways, which are subject to continuing uncertainties. The study highlights the augmentative effect of AP, a redox modulator, on hypoxic respiration, which may have a therapeutic potential.     

Observations on the hypoxic depression of sympathetic discharge in sinoaortic-denervated cats

The effect of graded isocapnic hypoxia on the mass activity of the cervical sympathetic trunk and of the phrenic nerve was studied in sinoaortic-denervated, pentobarbital-anaesthetized cats. Under control conditions (normoxia, normocapnia) sympathetic discharge showed (i) a burst of action potentials synchronous with the phrenic nerve burst, which was selectively abolished by procedures suppressing inspiratory neuron activity (inspiration synchronous sympathetic activity, ISSA); and (ii) a lower level of sympathetic activity during expiration (tonic sympathetic activity, TSA). The effects of graded hypoxia on these two components of the sympathetic discharge were different. ISSA showed depression only, which began at inspired PO2 (Pinsp O2) of 58 +/- 10 (mean +/- SEM) mmHg (1 mmHg = 133.3 Pa), became progressively more marked as Pinsp O2 decreased further, and was paralleled by depression of phrenic nerve activity. Both ISSA and phrenic nerve activity were suppressed at Pinsp O2 of 46 +/- 9 mmHg. TSA increased progressively with the lowering of Pinsp O2, beginning at a Pinsp O2 significantly lower than that at which ISSA depression began (50 +/- 13 mmHg, p less than 0.01). In the range of Pinsp O2 values intermediate between the thresholds for ISSA depression and for TSA increase, some animals showed a depression of TSA that reversed to an increase as Pinsp O2 decreased further. During brief (duration 1.5 +/- 0.2 min) episodes of cerebral ischemia produced by occlusion of the brachiocephalic and left subclavian artery, the two components of sympathetic discharge showed responses similar to those observed in hypoxia, namely depression of ISSA as well as depression and enhancement of TSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unique spectral peak in phrenic nerve activity characterizes gasps in decerebrate cats

The respiratory pattern of gasping has been characterized on the phrenic nerve as rapidonset, rapid-rise, large-amplitude bursts of neural activity. Furthermore, medullary sites critical for the neurogenesis of gasping have been identified and are not the sites of identified respiratory neurons, such as the dorsal and ventral respiratory groups. I classified envelopes of phrenic nerve activity as eupneic breaths, or gasps based on the time-domain features of duration, shape, and amplitude. Gasps were elicited by hypoxia and low blood pressure in 9 of 12 decerebrate cats. Inspiratory times were 1.15 +/- 0.43 (SD) for eupneic breaths and 0.55 +/- 0.18s for gasps. The high-frequency peaks in the power spectra of phrenic nerve activity were at 80 +/- 13 Hz for eupneic breaths and at 120 +/- 21 Hz for gasps. Three of the 12 cats developed a breathing pattern that began as a normal breath and terminated in a gasp. Power spectra of the normal portion had eupneic spectral peaks (75 +/- 24 Hz); power spectra of the gasp portion had the high peaks at 110 +/- 23 Hz, a value 1.5 times higher than that for the normal peaks. Although this analysis of peripheral nerve activity cannot distinguish between two central pattern generators at two distinct anatomical sites or one pattern generator operating in two distinct modes, the fact that gasps were much shorter in duration and had markedly higher spectral peaks than control breaths supports the idea that the central pattern generator for gasping is not the central pattern generator for eupnea.     

Synchronization of respiratory frequency by somatic afferent stimulation.

In cats anesthetized with chloralose-urethan, vagotomized, paralyzed, and artifically ventilated, superficial radial (cutaneous) and hamstring (muscle) nerve afferents were stimulated while phrenic nerve electrical activity was recorded. The results obtained with both types of nerves were similar. Stimulation in mid and late expiration advanced the onset of the next inspiration, shortening its duration. Stimulation in early inspiration advanced, while that in late inspiration delayed, the onset of the next expiration. These effects were often accompanied by changes in phrenic motoneuron firing patterns (earlier recruitment, increased discharge frequency, increased slope of integrated phrenic neurogram). Repetitive somatic afferent stimulation produced sustained increases in respiratory frequency in all cats and in half of them entrainment of respiratory frequency to the frequency of stimulation occurred at ratios such as 4:3, 4:5, 1:2, 1:3, 1:4, and 1:7. The lowest stimulus intensity required for evoking these phase shifts was between 5 and 10T (threshold of most excitable fibers) for muscle afferents and between 1 and 2T for cutaneous afferents. These results demonstrate the existence of a reflex mechanism capable of locking respiratory frequency to that of a periodic somatic afferent input. They also provide an experimental basis for the hypothesis that reflexes are resposible for the observed locking between step or pedal frequency and respiratory rate during exercise in man.     

Respiratory response to partial paralysis in anesthetized dogs

The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patterns of neural and muscular electrical activity in costal and crural portions of the diaphragm

To determine whether the central respiratory drives to costal and crural portions of the diaphragm differ from each other in response to chemical and mechanical feedbacks, activities of costal and crural branches of the phrenic nerve were recorded in decerebrate paralyzed cats, studied either with vagi intact and servo-ventilated in accordance with their phrenic nerve activity or vagotomized and ventilated conventionally. Costal and crural electromyograms (EMGs) were recorded in decerebrate spontaneously breathing cats. Hypercapnia and hypoxia resulted in significant increases in peak integrated costal, crural, and whole phrenic nerve activities when the vagi were either intact or cut. However, there were no consistent differences between costal and crural neural responses. Left crural EMG activity was increased significantly more than left costal EMG activity in response to hypercapnia and hypoxia. These results indicate that the central neural inputs to costal and crural portions of the diaphragm are similar in eupnea and in response to chemical and mechanical feedback in decerebrate paralyzed cats. The observed differences in EMG activities in spontaneously breathing animals must arise from modulation of central respiratory activity by mechanoreceptor feedback from respiratory muscles, likely the diaphragm itself.