Motor features of voluntary cough following partial laryngectomy for glottal carcinoma.

BACKGROUND: Aspiration and respiratory tract infections are commonly observed in patients following conservative laryngeal surgery such as supracricoid laryngectomy with cricohyoidopexy (CHP). Since laryngeal closure is important for cough effectiveness, we hypothesised that CHP reduced cough intensity by affecting the cough motor pattern. METHODS: In ten male patients with laryngeal cancer eligible for CHP, we assessed the intensity of maximum voluntary cough (MVC) prior to and 2 months after surgery. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGp) and the ratio of IEMGp to the duration of the expiratory ramp during cough (TEC), i.e. the rate of rise of IEMG activity (IEMGp/ TEC). For each cough effort, the duration of the compressive phase (CP), the cough peak flow (CPF), the time elapsed from the onset of cough to CPF (TTP) and their ratio, i.e. the volume acceleration (VA), were also evaluated. RESULTS: CHP did not affect IEMG-related variables; in contrast, it reduced (p < 0.01) CPF, CP and lengthened (p < 0.05) TTP values. In consequence, cough VA values after CHP were consistently lower than in control condition. CONCLUSIONS: Supracricoid laryngectomy with CHP alters the intensity of voluntary cough as indexed by flow-related variables. This may reduce cough efficiency and facilitate the onset and/or persistence of chest infections (Tab. 2, Fig. 1, Ref. 22).

Voluntary and reflex cough and the expiration reflex; implications for aspiration after stroke.

Aspiration is a common result of stroke, and may lead to lung infections and pneumonia. Cough may prevent this aspiration and thus prevent the pneumonia. We review the four types of cough usually used to assess aspiration risk: voluntary cough (VC), reflex cough (RC), the laryngeal expiration reflex (LER), and cough on swallow (CoS). VC is easy to test but starts with an inspiration that may cause aspiration, and is controlled by cortico-brainstem pathways that may not be involved in influencing aspiration. RC also starts with an inspiration, and requires instrumental intervention, but is more relevant to protecting the lungs. The LER starts with an expiration, so is 'anti-aspiration', and is easy to test, but its neural mechanisms have not been fully analysed. CoS can be tested at the same time as direct observations of aspiration, but little is known about its neural mechanisms. Each method has its advocates, and the purpose of the review is to discuss how each may be applied and how the information from each may be assessed and valued.

Cough. 3: chronic cough and gastro-oesophageal reflux.

The pathogenesis and clinical features of gastro-oesophageal reflux related cough are complex and the diagnostic tests available are of limited reliability. Treatment needs to be tailored to the specific needs of individual patients and other possible causes of chronic cough should be investigated. Treatment should only be considered to have failed when cough persists after administration of proton pump inhibitors at an adequate dosage for a sufficient length of time.

Fog-induced respiratory responses are attenuated by nedocromil sodium in humans.

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.

Respiratory neuronal activity during apnea and poststimulatory effects of laryngeal origin in the cat.

We investigated the behavior of medullary respiratory neurons in cats under pentobarbitone anesthesia, vagotomized, paralysed, and artificially ventilated to elucidate neural mechanisms underlying apnea and poststimulatory respiratory depression induced by superior laryngeal nerve (SLN) stimulation. Inspiratory neurons were completely inhibited during SLN stimulation and poststimulatory apnea. During recovery of inspiratory activity, augmenting inspiratory neurons were depressed, decrementing inspiratory neurons were excited, and late inspiratory neurons displayed unchanged bursts closely locked to the end of the inspiratory phase. Augmenting expiratory neurons were either silenced or displayed different levels of tonic activity during SLN stimulation; some of them were clearly activated. These expiratory neurons displayed activity during poststimulatory apnea, before the onset of the first recovery phrenic burst. Postinspiratory or decrementing expiratory neurons were activated during SLN stimulation; their discharge continued with a decreasing trend during poststimulatory apnea. The results support the three-phase theory of rhythm generation and the view that SLN stimulation provokes a postinspiratory apnea that could represent the inhibitory component of respiratory reflexes of laryngeal origin, such as swallowing. In addition, because a subpopulation of augmenting expiratory neurons displays activation during SLN stimulation, the hypothesis can be advanced that not only postinspiratory, or decrementing expiratory neurons, but also augmenting expiratory neurons may be involved in the genesis of apnea and poststimulatory phenomena. Finally, the increase in the activity of decrementing inspiratory neurons after the end of SLN stimulation may contribute to the generation of poststimulatory respiratory depression by providing an inhibitory input to bulbospinal augmenting inspiratory neurons.

Coughing in laryngectomized patients.

Ablation of the larynx implies withdrawal of afferent information from receptors involved both in the control of expiratory flow and in the genesis of protective airway reflexes including coughing. To investigate the effects of laryngectomy on the sensory and motor component of coughing, maximal voluntary cough (MVC) efforts as well as the reflex cough (RC) responses at threshold (T) and suprathreshold (1.8 x T, ST) levels induced by inhalation of progressively increasing concentrations of ultrasonically nebulized distilled water (fog) were analyzed in 10 laryngectomized patients and 10 control subjects. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGP) and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity (IEMGP/TEC). Cough peak flow was also recorded. Cough threshold was similar in patients and controls, as were IEMGP, TEC, and IEMGP/ TEC recorded during MVC and RCST. In contrast, during RCT, patients' IEMGP was significantly reduced (p < 0.05), thus leading to a significant decrease in IEMGP/TEC (p < 0.05) even in the absence of significant differences in TEC. Cough flow closely correlated with IEMG-related variables. Cough volume acceleration, i. e., the ratio of cough peak flow to the corresponding time to cough peak flow was also significantly reduced in the patients, especially during RCT (p < 0.01). The results suggest that the lack of signals arising from the larynx may result in a reduction of cough volume acceleration as well as in the intensity of abdominal muscle contractions during RCT. These factors may contribute to facilitate the onset and/or the persistence of chest infections in laryngectomized patients.

Repeatability of cough-related variables during fog challenges at threshold and suprathreshold stimulus intensity in humans.

Cough-related variables such as cough frequency, time to onset (i.e. the time until the first cough occurs) and the cough index (i.e. the ratio between the cough frequency and the time to onset) may be important when interpreting results of cough challenges for therapeutic interventions or for comparative research purposes. Nevertheless, repeatability (or reproducibility) for these widely used variables has been poorly studied. In thirty normal subjects, coughing was induced by inhalation of threshold (T) and suprathreshold (1.6 x T) concentrations of ultrasonically nebulized distilled water (fog). Cough threshold was taken as the lowest fog concentration that evoked at least one cough effort during two challenges separated by a 30-min interval. During challenges performed at both threshold and suprathreshold stimulus intensity, cough frequency, time to onset, and the cough index were assessed; within-subject repeatability for these variables was subsequently evaluated. Median +/- interquartile range cough threshold value was 0.9+/-0.5 mL x min(-1). During the two challenges performed to assess cough threshold, the mean +/-SD values of cough frequency, time to onset, and cough index were similar (5.0+/-2.7 and 5.3+/-3.1 coughs x min(-1), 32.4+/-13.3 and 32.9+/-13.6 s, and 0.2+/-0.2 and 0.2+/-0.2, respectively). However, none of these cough-related variables proved to be sufficiently repeatable. During the two challenges performed at suprathreshold stimulus intensity, mean values of cough frequency, time to onset, and cough index were also similar (20.0+/-9.0 and 18.2+/-10.2 coughs x min(-1), 13.5+/-5.8 and 12.0+/-4.62 s, and 1.7+/-1.0 and 1.8+/-1.2); furthermore, all considered variable of suprathreshold challenge turned out to be reproducible. In conclusion, during fog challenges at threshold stimulus intensity, cough frequency, time to onset and cough index cannot reliably be used for evaluating cough responses. However, these cough-related variables may represent useful and reliable research tools in the evaluation of suprathreshold cough responses.

Large and small airway responses to procaterol hydrochloride administered through different extension devices in asthmatic patients.

The effects of spacer devices on the magnitude and velocity of large and small airway bronchodilator responses in asthmatic patients who can correctly operate a metered dose inhaler (MDI) remain unclear. According to a double-blinded, randomized, crossover protocol, 14 asthmatic patients were studied on seven separate occasions. On each occasion, patients inhaled doubling methacholine concentrations until forced expiratory volume in 1 second (FEV1) had fallen by 20% of baseline. Changes in forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) were also evaluated. Subsequently, patients were administered 20 or 50 micrograms of procaterol from an MDI either alone or in conjunction with a small- or large-volume spacer device. Changes in FEV1 and FEF25-75 corrected for baseline forced vital capacity (isoFEF25-75) were assessed at 3-minute intervals for 15 minutes and at 30 minutes. Spontaneous recovery was similarly evaluated. The time required to attain significant increases in both FEV1 and isoFEF25-75 was calculated in bronchodilator trials. With 20 micrograms of procaterol, both spacers allowed larger and faster FEV1 increases than the MDI alone (P < 0.01); with 50 micrograms, the velocity and magnitude of FEV1 increases were further enhanced in trials with the MDI alone. The lower procaterol dose via the large-volume spacer determined larger and faster isoFEF25-75 increases than the higher dose via both the small-volume spacer and the MDI alone (P < 0.01). Spacers enhance bronchodilation even in patients using MDIs optimally. Compared with both the small-volume device and the MDI alone, the large-volume spacer allows faster and larger small airway dilation with less than half of the procaterol dose.

Defective motor control of coughing in Parkinson's disease.

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.

Discharge patterns of Bötzinger complex neurons during cough in the cat.

This study was carried out on pentobarbital sodium-anesthetized, spontaneously breathing cats to address the hypothesis that Bötzinger complex (BötC) neurons are involved in the production of the cough motor pattern induced by mechanical stimulation of the tracheobronchial tree. Phrenic nerve and abdominal muscle activities as well as intratracheal pressure were monitored; single-unit extracellular recordings from BötC neurons (n = 87) were performed. The majority of augmenting expiratory (E-Aug) neurons encountered (n = 47) displayed excitatory responses during the expulsive phases of coughing in parallel with the main components of the abdominal bursts and the corresponding increases in tracheal pressure. We also encountered E-Aug neurons markedly depressed up to complete inhibition during coughing (n = 14) as well as E-Aug neurons assuming a decremental pattern without any increase or even with some reduction in their peak activity (n = 15). During the expiratory thrusts, most decrementing expiratory neurons (n = 7) presented excitatory responses, whereas others were depressed (n = 3) or completely inhibited (n = 1). The results are consistent with the view that these neurons are involved in the generation of the cough motor pattern and, in particular, that some BötC E-Aug neurons convey excitatory drive to caudal expiratory neurons and, hence, to expiratory motoneurons.

A noninvasive electromyographic study on threshold and intensity of cough in humans.

The assessment of cough threshold and intensity is important in respiratory medicine. We have developed a method for objectively and noninvasively assessing cough threshold and intensity of expiratory muscle efforts in response to inhalation of ultrasonically nebulized distilled water (UNDW). Thirty (83%) out of 36 volunteers studied coughed in response to UNDW inhalation. Cough threshold was taken as the lowest nebulizer output (mL x min(-1)) that induced cough in two challenges performed at a 30 min interval. At threshold level, repeatability of peak and slope of the integrated electromyographic (IEMG) activity of abdominal muscles was evaluated. Short- and long-term repeatability of cough threshold were evaluated in 15 subjects following a 3 h and a 6-9 month interval, respectively. Dose-response relationships between nebulizer outputs and IEMG-related variables were also investigated, as were the correlations between the latter and expiratory flow during voluntary coughing. The median (1st and 3rd quartile) cough threshold value was 0.89 (0.40 and 1.54) mL x min(-1). At threshold level, peak and slope of IEMG activity were highly reproducible. Cough threshold displayed a high degree of short- and long-term repeatability. Peak and slope of IEMG activity displayed a clear trend to increase (p<0.01) following inhalation of progressively higher UNDW outputs. Maximum flow during voluntary coughs of varying intensity correlated with the peak (p<0.05) and, more closely, with the slope (p<0.01) of abdominal IEMG activity. The assessment of cough threshold as well as the evaluation of the intensity of cough efforts by abdominal integrated electromyographic recordings may represent useful and reliable tools for cough research in humans.

Effects of central chemical drive on poststimulatory respiratory depression of laryngeal origin in the adult cat.

We investigated the influences of central CO2-related chemosensory drive on poststimulatory respiratory phenomena induced by superior laryngeal nerve (SLN) stimulation in pentobarbitone-anesthetized, vagotomized, carotid sinus-denervated, paralyzed, and artificially ventilated adult cats. Respiratory output was monitored as integrated phrenic nerve activity. Under eucapnic conditions, apnea-producing SLN stimulations of both short (10 s) and long (30 s) duration were followed by persistent apnea and depression in phrenic motor output; the latter showed a gradual recovery that followed an exponential time course. Hypocapnia increased the duration of poststimulatory apnea and the intensity of poststimulatory depression in phrenic minute output owing to changes in peak phrenic activity. Hypercapnia did not affect the duration of poststimulatory apnea, but markedly attenuated poststimulatory depression in respiratory activity, mainly due to changes in respiratory frequency. The rate of respiratory recovery was similar under eucapnic and hypocapnic conditions, but it was slower during hypercapnia. The results provide evidence that central chemosensitivity plays a prominent role in counteracting poststimulatory depressant effects on respiration induced by SLN stimulation.

Naloxone attenuates poststimulatory respiratory depression of laryngeal origin in the adult cat.

Poststimulatory depression in respiratory activity induced by superior laryngeal nerve (SLN) stimulation was quantitatively investigated in 20 adult cats. The role played in this phenomenon by endogenous opioids was studied using the opiate antagonist naloxone. The effects of hypercapnia on the same phenomenon were also investigated for comparison. Experiments were performed on cats anesthetized with pentobarbitone or alpha-chloralose, vagotomized, paralyzed, and artificially ventilated with 100% O2. Some animals were also carotid sinus denervated. Respiratory output was monitored as integrated phrenic nerve activity. SLN stimulation produced apnea, which outlasted the stimulation period; when respiration resumed, it was markedly depressed as revealed mainly by a decrease in phrenic minute output, respiratory frequency, and rate of rise of inspiratory activity. Phrenic output recovered gradually to control levels following an exponential time course. These effects varied as a function of the duration of SLN stimulation. Naloxone administration (0.8 mg/kg iv) significantly reduced the duration of poststimulatory apnea and attenuated the depression of phrenic minute output of the first recovery breath as a result of changes in peak phrenic activity; it also accelerated the time course of recovery. Hypercapnia did not affect the duration of poststimulatory apnea, but attenuated the initial poststimulatory depression because of changes in respiratory frequency; the rate of recovery was reduced. The results provide characterization of poststimulatory respiratory depression of laryngeal origin in the adult cat and suggest a role of endogenous opioids in its genesis or modulation.

Prostaglandin synthesis blockade by ketoprofen attenuates respiratory and cardiovascular responses to static handgrip.

We investigated the effects of prostaglandin synthesis blockade on the changes in breathing pattern, mean blood pressure (MBP), and heart rate (HR) elicited by 3 min of static handgrip at 30% of the maximum voluntary contraction in 12 healthy volunteers. Before each handgrip trial, subjects were treated with intravenous administration of either saline placebo (control) or 1 mg/kg of ketoprofen. Muscle tension and integrated electromyographic activity of exercising muscles remained fairly constant during each trial. In agreement with our earlier findings, during control handgrip minute ventilation progressively increased (P < 0.01) due to a rise in tidal volume and, to a lesser extent, in respiratory frequency. Mean inspiratory flow, MBP, and HR also increased (P < 0.01). End-tidal PCO2 decreased (P < 0.05) during the late phases of control handgrip bouts. Ketoprofen administration reduced serum thromboxane B2 levels (from 57.5 +/- 7.0 to 1.6 +/- 0.4 pg/ml; P < 0.01) and significantly attenuated mean increases in minute ventilation (40.25 +/- 0.60%), tidal volume (37.78 +/- 7.48%), respiratory frequency (55.94 +/- 17.92%), inspiratory flow (42.66 +/- 5.11%), MBP (22.33 +/- 6.82%), and HR (11.04 +/- 2.75%) during the 3rd min of handgrip. End-tidal PCO2 remained close to normocapnic levels. In agreement with previous animal investigations, the present results show that arachidonic acid metabolites are involved in the regulation of the cardiovascular responses to static efforts in humans, possibly through a stimulatory action on muscle receptors. Furthermore, they provide the first experimental evidence that products of the cyclooxygenase metabolic pathway play a role in the mediation of the respiratory adjustments elicited by this form of exercise.

Comparison of dose-response slopes obtained by simultaneous assessment of changes in FEV1 and transcutaneous oxygen partial pressure during methacholine challenges in asthmatic patients.

We aimed to ascertain whether monitoring changes in transcutaneous (tc) oxygen partial pressure (PO2) may be used to determine the slope of the dose-response curves to inhaled methacholine. In 10 adult asthmatic patients, FEV1 and tcPO2 were simultaneously measured during inhalation of doubling methacholine concentrations. In each patient, the slopes of the methacholine dose-response curves for FEV1 and tcPO2 were similar and strongly correlated (r = 0.72; p < 0.05). The results indicate that tcPO2 monitoring represents a useful, reliable tool for analysis of the slope of dose-response curves to inhaled methacholine in asthmatic patients. It can also be used to investigate the pathophysiological implications of bronchial hyperreactivity.

Chemical activation of caudal medullary expiratory neurones alters the pattern of breathing in the cat.

1. The purpose of this work was to ascertain whether the activation of caudal expiratory neurones located in the caudal part of the ventral respiratory group (VRG) may affect the pattern of breathing via medullary axon collaterals. 2. We used microinjections of DL-homocysteic acid (DLH) to activate this population of neurones in pentobarbitone-anaesthetized, vagotomized, paralysed and artificially ventilated cats. Both phrenic and abdominal nerve activities were monitored; extracellular recordings from medullary and upper cervical cord respiratory neurones were performed. 3. DLH (160 mM) microinjected (10-30 nl for a total of 1.6-4.8 nmol) into the caudal VRG, into sites where expiratory activity was encountered, provoked an intense and sustained activation of the expiratory motor output associated with a corresponding period of silence in phrenic nerve activity. During the progressive decline of the activation of abdominal motoneurones, rhythmic inspiratory activity resumed, displaying a decrease in frequency and a marked reduction or the complete suppression of postinspiratory activity as its most consistent features. 4. Medullary and upper cervical cord inspiratory neurones exhibited inhibitory responses consistent with those observed in phrenic nerve activity, while expiratory neurones in the caudal VRG on the side contralateral to the injection showed excitation patterns similar to those of abdominal motoneurones. On the other hand, in correspondence to expiratory motor output activation, expiratory neurones of the Bötzinger complex displayed tonic discharges whose intensity was markedly lower than the peak level of control breaths. 5. Bilateral lignocaine blockades of neural transmission at C2-C3 affecting the expiratory and, to a varying extent, the inspiratory bulbospinal pathways as well as spinal cord transections at C2-C3 or C1-C2, did not suppress the inhibitory effect on inspiratory neurones of either the ipsi- or contralateral VRG in response to DLH microinjections into the caudal VRG. 6. The results show that neurones within the column of caudal VRG expiratory neurones promote inhibitory effects on phrenic nerve activity and resetting of the respiratory rhythm. We suggest that these effects are mediated by medullary bulbospinal expiratory neurones, which may, therefore, have a function in the control of breathing through medullary axon collaterals.

Respiratory and cardiovascular responses to static handgrip exercise in humans.

We studied the time course of respiratory and cardiovascular responses by evaluating changes in the breathing pattern, mean blood pressure (MBP), and heart rate elicited by 3 min of static handgrip at 15, 25, and 30% of the maximum voluntary contraction (MVC) in 15 healthy volunteers. Muscle tension and integrated electromyographic activity remained fairly constant during each trial. During 15% MVC bouts, initially only mean inspiratory flow increased; then, tidal volume and minute ventilation (VI) also rose progressively. No significant changes in MBP and heart rate were observed. During 25 and 30% MVC bouts, not only did mean inspiratory flow, VT, and VI increase but MBP and heart rate increased as well. A slight and delayed rise in respiratory rate was also observed. Unlike 15 and 25% MVC handgrip, 30% MVC handgrip caused a small decrease in end-tidal PCO2. Changes in the pattern of breathing occurred more promptly than those in cardiovascular variables in the majority of subjects. Furthermore, we found a positive correlation between changes in VI and those in cardiovascular variables at the end of 25 and 30% MVC trials. This study indicates that respiratory and cardiovascular responses to static handgrip exercise are controlled independently.

Excitatory and depressant respiratory responses to chemical stimulation of the rostral ventrolateral medulla in the cat.

The rostral ventrolateral medulla (rVLM) is known to play an important role in cardiorespiratory control. In the rVLM an 'apnoea region', in which unilateral focal blocks induce strong depressant effects on inspiratory activity up to complete apnoea, has been described. This study was designed to systematically investigate the effects provoked by unilateral micro-injections (10-30 nl) of D,L-homocysteic acid 160 mM into this region on respiratory activity and arterial blood pressure in pentobarbitone anaesthetized, vagotomized, paralyzed and artificially ventilated cats. Micro-injections into the rostral portion of this area caused depressant respiratory responses up to complete apnoea, while micro-injections into more caudally located sites induced excitatory respiratory responses. Similar effects were observed in the activity of phrenic nerves and inspiration-related medullary neurons of both the dorsal and ventral respiratory group. The respiratory responses could be accompanied by marked increases in blood pressure (> or = 30 mmHg), especially at locations ventral to the retrofacial and facial nucleus; however, they could also occur in the absence of appreciable changes or even in association with slight decreases in blood pressure. Similar respiratory and pressor effects were observed in carotid sinus denervated cats. The results indicate that two distinct rVLM neuronal populations, one located more rostrally and the other more caudally, may have an important role in the genesis and/or maintenance of respiratory rhythm by exerting respectively inhibitory and excitatory influences on inspiratory activity. Furthermore, they support the hypothesis that different neural substrates of the rVLM are involved in the regulation of respiratory and cardiovascular functions.