RESUMEN
1. Arousal from sleep is associated with transient stimulation of ventilation above normal waking levels that predisposes to subsequent breathing instability and central apnoea. The transient hyperpnoea at arousal is normally explained by differences in arterial partial pressure of CO(2) (P(a,CO2)) between sleep and wakefulness, with a higher P(a,CO2) in sleep leading to stimulation of ventilation at arousal according to the awake ventilatory response to CO(2). Surprisingly, however, the validity of this current model in fully explaining the increased ventilation at arousal from sleep has not been directly tested. 2. This study tests the hypothesis that the level of ventilation at arousal from non-rapid eye movement (non-REM) sleep is greater than that produced by elevating P(a,CO2) in wakefulness to the sleeping level, i.e. the ventilation predicted by the current model. 3. Studies were performed in five dogs. Inspired CO(2) was used to increase end-tidal partial pressure of CO(2) (P(ET,CO2)) in wakefulness and measure the ventilatory response. The same P(ET,CO2) was then maintained in non-REM sleep. Ventilation was measured for 10 breaths before and after arousal from non-REM sleep induced by a 72 dB tone. 4. Arousal from sleep produced a transient surge in ventilation of 1.42 +/- 0.35 l min(-1) (P = 0.005). This increased ventilation was due to arousal from sleep per se as the tone alone produced no change in awake ventilation. In support of the hypothesis, ventilation at wake onset from sleep was greater by 0.83 +/- 0.28 l min(-1) (P = 0.031) than the ventilation elicited in wakefulness by raising P(ET,CO2) to the sleeping level. 5. The results show that > 50 % of the increase in ventilation at wake onset from sleep is not attributable to the awake ventilatory response to the elevated P(a,CO2) that was previously present in sleep. This result leads to important modifications of the physiological model currently used to explain the ventilatory consequences of arousal from sleep.
Asunto(s)
Nivel de Alerta/fisiología , Dióxido de Carbono/sangre , Fenómenos Fisiológicos Respiratorios , Sueño/fisiología , Vigilia/fisiología , Animales , Arterias , Perros , Femenino , Frecuencia Cardíaca/fisiología , Masculino , Presión Parcial , Fases del Sueño/fisiología , Volumen de Ventilación Pulmonar , Factores de TiempoRESUMEN
We used a canine model of chronic obstructive sleep apnea (OSA) to examine the effects of intermittent airway occlusion during sleep on left ventricular (LV) performance. Studies were performed in four dogs. The effects of acute airway occlusion on LV pressure and volume (on a background of chronic OSA) were determined with an impedance catheter and a high fidelity manometer. In conscious animals (n = 3), experiencing spontaneous episodes of sleep, acute airway occlusion caused significant increases in LV transmural systolic pressure that were associated with increased end-systolic volume and reduced stroke volume. To determine the effects of chronic OSA on baseline LV function, two-dimensional echocardiograms were performed in conscious animals (n = 4) during unobstructed breathing before and after a 1- to 3-mo period of OSA. During chronic OSA, there was a significant decrease in LV ejection fraction as a result of increases in end-systolic volume. We conclude that in chronic OSA acute airway occlusion during sleep is associated with increases in LV afterload and decreases in fractional shortening. Chronic OSA also leads to sustained decreases in LV systolic performance that could be caused by the development of systemic hypertension and/or transient increases in LV afterload during episodes of airway obstruction.
Asunto(s)
Obstrucción de las Vías Aéreas/fisiopatología , Función Ventricular Izquierda , Animales , Volumen Cardíaco , Enfermedad Crónica , Perros , Ecocardiografía , Femenino , Masculino , Contracción Miocárdica , Apnea Obstructiva del Sueño/fisiopatología , Volumen Sistólico , Presión VentricularRESUMEN
We have recently demonstrated the development of systemic hypertension in a canine model of obstructive sleep apnea (OSA), but the underlying physiological mechanisms were not identified. Therefore, the purpose of this study was to examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in this canine model. OSA was produced in three dogs for 1 to 3 mo. Baroreflex control of HR was determined with graded infusions of vasoactive agents (phenylephrine and nitroprusside) administered over 30 to 60 s, during which steady-state systolic blood pressure (BP) and cardiac R-R interval responses were recorded. BP was measured with a permanently implanted arterial catheter and a telemetry system. Although, as previously reported, OSA resulted in increases in daytime (awake) mean BP of 6.0 to 26.8 mm Hg, there was no change in daytime baseline HR or in the slope of the systolic BP-R-R interval curve (p > 0.2). The findings demonstrate that OSA in the dog is associated with resetting of the baroreceptors to a higher pressure, but no change in baroreflex sensitivity.
Asunto(s)
Barorreflejo/fisiología , Frecuencia Cardíaca , Síndromes de la Apnea del Sueño/fisiopatología , Animales , Presión Sanguínea , Perros , Femenino , MasculinoRESUMEN
Obstructive sleep apnea (OSA) causes recurrent sleep disruption that is thought to contribute to excessive daytime sleepiness in patients with this disorder. The purpose of this study was to determine the specific effects of OSA on overall sleep architecture in a canine model of OSA. The advantage of this model is that sleep during long-term OSA can be compared to both normal sleep before OSA and recovery sleep after OSA. Studies were performed in four dogs in which sleep-wake state was monitored continuously by a computer that received telemetered EEG and EMG signals. Whenever sleep was detected, the computer sent a signal to close a valve through which the dog breathed; when the dog awoke the occlusion was released. In each dog, data were analyzed from 4 consecutive nights in three phases: a control phase before induction of OSA, a phase during long-term OSA (mean = 85 days, apnea index = 59/hour), and a recovery phase after cessation of OSA. During recovery there was a significant increase in the amount of rapid-eye-movement (REM) sleep compared to the OSA phase (p < 0.01), as well as significant increases in sleep efficiency and decreases in wakefulness (p < 0.01), similar to that reported in OSA patients. The REM rebound during recovery, however, could not be attributed to overall REM deprivation since the amount of REM sleep during the OSA phase was not different from the control phase (p = 0.708). This finding suggests that REM rebound during recovery from OSA is not the result of an overall REM sleep deficit per se. Rather, repeated sleep disruption due to the effects of repetitive apneas and hypoxia may lead to an increased REM sleep drive that manifests itself as a REM sleep rebound during recovery sleep after OSA.
Asunto(s)
Síndromes de la Apnea del Sueño/diagnóstico , Sueño REM/fisiología , Animales , Modelos Animales de Enfermedad , Perros , Electroencefalografía , Electromiografía , Femenino , Masculino , Respiración con Presión Positiva/métodos , Síndromes de la Apnea del Sueño/terapiaRESUMEN
We have previously described a canine model of obstructive sleep apnea (OSA) in which sleep-wake state is monitored continuously by a computer that produces tracheal occlusion when sleep occurs. Our aim was to assess the effects of long-term application of this model on resting ventilation and on the ventilatory and arousal responses to hypercapnia and hypoxia. Five dogs were maintained on the model for 15.5 +/- 1.7 (mean +/- SE) wk, with a mean apnea index of 57.5 +/- 4.5 occlusions/h of sleep. Resting ventilation and the ventilatory and arousal responses to progressive hypoxic and hypercapnic rebreathing were assessed during wakefulness (W) and both slow-wave (SWS) and rapid-eye-movement (REM) sleep at baseline prior to intervention, at the end of the OSA phase, and following a 1 to 3-mo recovery period. During the period of OSA there were small changes in respiratory timing at rest, but no significant changes in PCO2 or SaO2. As compared with baseline, the ventilatory response to hypoxia during OSA was strikingly reduced during W, and significantly although less markedly reduced during SWS and REM. The reduction was due to a decreased breathing frequency response to hypoxia. In addition, during OSA there was a significant decrease from baseline in SaO2 at arousal during hypoxic rebreathing in both SWS and REM. All responses returned to normal during recovery. In contrast to hypoxia, hypercapnic ventilatory responses during OSA were slightly increased over their baseline values both in W and SWS, owing to a leftward shift of the ventilation-versus-PCO2 relationship. During recovery, these responses reverted partly to baseline for W and reverted completely to baseline for SWS. There were no significant changes in arousal PCO2 during hypercapnic rebreathing in either SWS or REM across the pre-OSA baseline, OSA, and post-OSA recovery periods. We conclude that long-term application of the OSA model is associated with a selective, reversible decrease in ventilatory and arousal responses to hypoxia.
Asunto(s)
Nivel de Alerta/fisiología , Modelos Animales de Enfermedad , Hipercapnia/fisiopatología , Hipoxia/fisiopatología , Síndromes de la Apnea del Sueño/fisiopatología , Volumen de Ventilación Pulmonar/fisiología , Animales , Análisis de los Gases de la Sangre , Perros , Estudios de Factibilidad , Hipercapnia/complicaciones , Hipoxia/complicaciones , Polisomnografía , Síndromes de la Apnea del Sueño/complicaciones , Fases del Sueño/fisiología , Factores de Tiempo , Vigilia/fisiologíaRESUMEN
Although the acute physiologic responses to apnea in patients with obstructive sleep apnea (OSA) have been well documented, the changes in these responses over the course of the disease have not been investigated. The purpose of this study was to use a canine model of OSA to examine the long-term effects of sleep apnea on the acute responses to airway occlusion during sleep. Four dogs were studied during a control period before induction of OSA, during a period of OSA (83-133 d), and following cessation of OSA. At least 6 mo after completion of the OSA protocol, the dogs were re-studied on a sleep fragmentation protocol (30-60 d) to determine the impact of a similar degree of sleep disruption, without OSA, on the acute responses to airway occlusion. OSA and sleep fragmentation both resulted in lengthening of the time to arousal in response to acute airway occlusion (p < 0.02) and in greater arterial oxygen desaturation (p < 0.05), peak inspiratory pressures (p < 0.003), and surges in maximum systolic and diastolic blood pressure during airway occlusion (p < 0.01). There were no differences between the changes observed during OSA and during sleep fragmentation. We conclude that the changes in the acute responses to airway occlusion resulting from OSA are primarily the result of the associated sleep fragmentation.
Asunto(s)
Obstrucción de las Vías Aéreas/fisiopatología , Síndromes de la Apnea del Sueño/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Animales , Nivel de Alerta , Presión Sanguínea , Perros , Electrocardiografía , Electroencefalografía , Femenino , Masculino , Fases del SueñoRESUMEN
Several epidemiological studies have identified obstructive sleep apnea (OSA) as a risk factor for systemic hypertension, but a direct etiologic link between the two disorders has not been established definitively. Furthermore, the specific physiological mechanisms underlying the association between OSA and systemic hypertension have not been identified. The purpose of this study was to systematically examine the effects of OSA on daytime and nighttime blood pressure (BP). We induced OSA in four dogs by intermittent airway occlusion during nocturnal sleep. Daytime and nighttime BP were measured before, during, and after a 1-3-mo long period of OSA. OSA resulted in acute transient increases in nighttime BP to a maximum of 13.0+/-2.0 mmHg (mean+/-SEM), and eventually produced sustained daytime hypertension to a maximum of 15.7+/-4.3 mmHg. In a subsequent protocol, recurrent arousal from sleep without airway occlusion did not result in daytime hypertension. The demonstration that OSA can lead to the development of sustained hypertension has considerable importance, given the high prevalence of both disorders in the population.
Asunto(s)
Presión Sanguínea/fisiología , Hipertensión/complicaciones , Hipertensión/etiología , Síndromes de la Apnea del Sueño/complicaciones , Animales , Perros , Femenino , Masculino , Privación de Sueño , Vigilia/fisiologíaRESUMEN
We have used an implanted telemetry system to continuously monitor blood pressure (BP) in three dogs for durations ranging from 28 to 75 wk after implantation. Measurements of BP obtained by telemetry were compared every 3-12 wk, with measurements of BP recorded with a manometer-tipped catheter that was inserted into a femoral artery. Over a wide range of both physiological and pharmacologically manipulated pressures (40-200 mmHg), the values of BP obtained by the two methods were highly correlated (all r > 0.966; all P < or = 0.0001). However, the mean differences between the values obtained by the two systems were different from zero (range +29.6 to -1.5 mmHg; P < or = 0.0001), indicating an offset in the BP values recorded from the implanted system. Furthermore, this offset was dependent on the absolute level of the BP. The findings indicate that, for a period of at least 28 wk and up to 75 wk after implantation, the telemetry system accurately measures acute changes in BP and can reliably measure absolute BP provided that the system is properly validated.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial/instrumentación , Monitoreo Ambulatorio de la Presión Arterial/métodos , Telemetría/instrumentación , Telemetría/métodos , Animales , Presión Sanguínea/fisiología , Calibración , Perros , Electroencefalografía , Electromiografía , Femenino , Frecuencia Cardíaca/fisiología , Reproducibilidad de los ResultadosRESUMEN
To determine the immediate effects of arousal from non-rapid-eye-movement (non-REM) sleep on cardiac sympathetic and parasympathetic activities, six dogs were studied breathing through an endotracheal tube inserted into a chronic tracheostomy. Mean heart rates (HRs) during non-REM sleep were compared with 1) awake periods immediately after spontaneous arousals (ARs) and 2) later periods of stable relaxed wakefulness (RW). During spontaneous breathing, HR increased after AR (mean = 31.0%; P < 0.001) and in RW (mean = 7.6%; P < 0.001). To avoid the confounding influence of changes in breathing pattern, lung volume, and blood gases accompanying AR on HR, further studies were performed during constant mechanical hyperventilation that eliminated spontaneous breathing. In this condition, HR still increased after AR (mean = 29.9%; P < 0.001) and in RW (mean = 5.7%; P < 0.001), suggesting that the HR increases could be mediated by an effect of the state change per se on autonomic activity. This interpretation was confirmed when the HR increases were essentially abolished by combined cardiac sympathetic and parasympathetic block. In contrast, parasympathetic block alone did not prevent the HR increases after AR (mean = 12.2%; P < 0.001) or in RW (mean = 12.3%; P < 0.001), whereas sympathetic block alone almost abolished the HR increases in RW (mean = 3.6%) but did not prevent the HR increases during AR (mean = 30.2%; P < 0.001). The results show that, compared with non-REM sleep, AR is associated with acute cardiac sympathetic activation and parasympathetic withdrawal, whereas stable RW is associated mainly with sympathetic activation. These effects may have clinical relevance to the cardiovascular sequelae of breathing disorders that cause repetitive arousals from sleep.
Asunto(s)
Apnea/fisiopatología , Nivel de Alerta/fisiología , Sistema de Conducción Cardíaco/fisiopatología , Sueño , Animales , Perros , Frecuencia Cardíaca , Bloqueo Nervioso , Ruido , Sistema Nervioso Parasimpático/fisiología , Respiración , Respiración Artificial , Fases del Sueño , Sistema Nervioso Simpático/fisiología , VigiliaRESUMEN
The aim of this study was to determine the mechanism(s) responsible for the persistence of respiratory sinus arrhythmia (RSA) during central apnea. In five awake dogs, heart rate (HR) was recorded during constant mechanical ventilation (MV) and during central apneas produced by cessation of MV. For each of 10 control ventilator cycles before MV was stopped, instantaneous HR was plotted against the time from the onset of lung inflation; the fundamental and first harmonic of a sine wave (at the ventilator frequency) was then fitted to the HR data. For the control cycles, the mean r2 from the curve fits was 0.57 +/- 0.07, showing that a significant component of the HR variability was linked to the ventilator cycle. After MV was stopped, RSA persisted and only by the third "phantom" ventilator cycle during apnea had the degree of fit consistently decreased compared with control dogs (P < 0.02). The persistence of ventilator-linked RSA at the onset of central apnea supports the concept of a "memory" in the respiratory system. Toward the end of central apnea, HR variability reappeared and had the periodicity and rhythmic profile of RSA on 81% of occasions. The presence of RSA-like activity toward the end of central apnea suggests that subthreshold rhythmic respiratory-related activity may be present even before the onset of detectable lung volume changes.
Asunto(s)
Arritmia Sinusal/fisiopatología , Frecuencia Cardíaca/fisiología , Síndromes de la Apnea del Sueño/fisiopatología , Animales , Perros , Hipocapnia/fisiopatología , Respiración/fisiología , Factores de TiempoRESUMEN
This report describes a canine model of obstructive sleep apnea (OSA) developed in our laboratory and the results of its preliminary short-term application. Healthy adult dogs were prepared with a tracheostomy and with implanted electroencephalographic and nuchal electromyographic recording electrodes. A silent occlusion valve was attached to the outer end of the endotracheal tube. The electroencephalogram and electromyogram were monitored continuously by a computer that determined sleep-wake state using software developed in our laboratory. At a predetermined time (e.g., 12 s) after each sleep onset, a signal was transmitted from the computer to the valve controller, resulting in airway occlusion. When the dog aroused from sleep, the occlusion was released. These events therefore mimic those that occur in human OSA. Successful operation of the model was confirmed during 5-day continuous trials in two dogs. During the trials, the dogs became increasingly somnolent both by behavioral observation and objective measurement. The frequency of occlusions increased, and measures of apnea severity, including apnea duration and end-apneic arterial oxygen saturation, worsened. We conclude that this experimental model of repeated airway occlusion during sleep provides a potentially powerful tool for investigating the sequelae of OSA.
Asunto(s)
Obstrucción de las Vías Aéreas/fisiopatología , Síndromes de la Apnea del Sueño/fisiopatología , Obstrucción de las Vías Aéreas/psicología , Animales , Conducta Animal/fisiología , Modelos Animales de Enfermedad , Perros , Electrodos Implantados , Electroencefalografía , Electromiografía , Consumo de Oxígeno/fisiología , Sueño/fisiología , Síndromes de la Apnea del Sueño/psicología , Sueño REM/fisiología , TelemetríaRESUMEN
1. The present study was designed to determine the effect of sleep on the tonic output to respiratory muscle and on the level of chemical respiratory stimulation required to produce rhythmic respiratory output. 2. Chronically implanted electrodes recorded expiratory (triangularis sterni) and inspiratory (diaphragm and parasternal intercostal) electromyographic (EMG) activities in three trained dogs during wakefulness and sleep. The dogs were mechanically hyperventilated via an endotracheal tube inserted into a permanent tracheostomy. During the studies, a cold block of the cervical vagus nerves was maintained to avoid the complicating effects of vagal inputs on respiratory drive and rhythm. 3. During wakefulness, steady-state hypocapnia (partial pressure of CO2, PCO2 = 30 mmHg) abolished inspiratory EMG activity, resulting in apnoea, but the expiratory muscle became tonically active. Compared to wakefulness, the level of the tonic expiratory EMG activity was decreased in non-REM (non-rapid eye movement) sleep (median decrease = 34%, P = 0.005) and was further decreased in REM sleep (median decrease = 78%, P < 0.0001). During REM sleep, the tonic expiratory EMG activity was highly variable (mean coefficient of variation = 39% compared to 7% awake, P < 0.0001) and in some periods of REM, bursts of inspiratory EMG activity and active breathing movements were observed despite the presence of hypocapnia. 4. During constant mechanical hyperventilation, progressive increases in arterial PCO2 (in hyperoxia) were produced by rebreathing. Measurement of the CO2 threshold for the onset of spontaneous breathing showed that this threshold was not different between wakefulness and non-REM sleep (mean difference = 0.1 mmHg from paired observations, 95% confidence interval for the difference = -1.0 to +1.1 mmHg, P = 0.898). 5. The results show that sleep reduces the tonic output to respiratory muscles but does not increase the CO2 threshold for the generation of rhythmic respiratory output. These observations suggest that changes in the tonic drives to the respiratory motoneurones may be a principal mechanism by which changes in sleep-wake states produce changes in respiratory output.
Asunto(s)
Respiración/fisiología , Músculos Respiratorios/fisiología , Sueño/fisiología , Animales , Apnea , Dióxido de Carbono/fisiología , Umbral Diferencial , Perros , Electrodos , Electromiografía , Hipocapnia , Respiración ArtificialRESUMEN
This study was designed to determine whether a chemoreceptor-mediated tonic respiratory drive exists below the apneic threshold. Expiratory (triangularis sterni) and inspiratory (diaphragm and parasternal intercostal) electromyographic activities were recorded in three awake relaxed dogs breathing through an endotracheal tube inserted into a permanent tracheostomy. The cervical vagus nerves were cold blocked to avoid the complicating effects of vagal inputs on respiratory activity. During hypocapnia produced by mechanical hyperventilation, expiratory muscle activity converted from rhythmic to tonic discharge when inspiratory muscle activity and spontaneous breathing movements were abolished. In hypocapnia, changes in arterial PCO2 (in hyperoxia) were produced by changing the ventilator rate for steady-state (> 6 min) CO2 stimuli and by disconnecting the ventilator for transient CO2 stimuli. By use of either method, a CO2-mediated drive to the expiratory muscle was consistently observed during hypocapnic apnea. At a constant level of hypocapnia, inhalation of 5% O2 consistently caused the onset of spontaneous breathing; the onset of phasic inspiratory activity was associated with reciprocal inhibition of the tonic expiratory activity. However, inhalation of 10 and 15% O2 caused an inhibition of the tonic expiratory activity, even without the onset of breathing. These results suggest that the response threshold of the respiratory chemoreceptors is lower than the apneic threshold and that a chemoreceptor-mediated tonic respiratory drive persists during apnea.
Asunto(s)
Apnea/fisiopatología , Periodicidad , Respiración/fisiología , Animales , Arterias , Dióxido de Carbono/sangre , Perros , Electromiografía , Hiperventilación/fisiopatología , Hipocapnia/sangre , Hipocapnia/fisiopatología , Bloqueo Nervioso , Presión Parcial , Respiración Artificial , Músculos Respiratorios/fisiología , Nervio VagoRESUMEN
We examined the effects of aging on the metabolic respiratory control system by measuring changes with time in steady-state minute volume of ventilation (VI), alveolar carbon dioxide pressure (PACO2), and ventilatory and arousal responses to hypercapnia and hypoxia during slow-wave sleep (SWS). Studies were performed longitudinally in six healthy dogs over a span of 3 to 7 yr, corresponding biologically to 12 to 24 human yr. In each of the dogs aging was associated with a decrease in steady state VI during SWS, from 6.53 +/- 1.08 (mean +/- SEM) to 5.56 +/- 0.90 L/min (p < 0.01), and with an increase in PACO2 from 36.2 +/- 1.0 to 38.5 +/- 1.1 mm Hg (p < 0.01). However, ventilatory and arousal responses to hyperoxic hypercapnia (four dogs) remained unchanged. In contrast there was a decrement in the response of VI to isocapnic hypoxia during SWS (five dogs), from 1.22 +/- 0.12 to 0.70 +/- 0.07 L/min/% fall in arterial O2 saturation (SaO2) (p < 0.02), and a decrease in arousal SaO2, from 83.3 +/- 3.2 to 73.5 +/- 2.3 percent (p < 0.001). The findings indicate that aging is accompanied by impairment of ventilatory and arousal responses to hypoxia during SWS, and point to a specific effect of aging on the carotid-body chemoreceptors, as opposed to the brainstem respiratory controller or the ventilatory pump.
Asunto(s)
Envejecimiento/fisiología , Respiración/fisiología , Sueño/fisiología , Animales , Perros , Femenino , Hipercapnia/fisiopatología , Hipoxia/fisiopatología , Estudios Longitudinales , Masculino , Oxígeno/administración & dosificación , Mecánica Respiratoria/fisiologíaRESUMEN
Chemical respiratory stimuli can induce arousal from sleep, but the specific mechanisms involved have not been established. Therefore, we tested the hypothesis that mechanoreceptor stimuli arising in the ventilatory apparatus have a role in the arousal responses to progressive hypercapnia and hypoxia by comparing arousal responses during spontaneous ventilation with those obtained when the inspiratory muscles were unloaded by mechanical ventilatory assistance. Studies were performed in three trained dogs in which the adequacy of inspiratory muscle unloading was verified by diaphragmatic electromyographic (EMG) recordings. In rapid-eye-movement (REM) sleep the arousal threshold during progressive hypercapnia increased from 68.4 +/- 0.5 (SE) mmHg during spontaneous runs to 72.3 +/- 0.8 mmHg during mechanically assisted runs (P < 0.01). In contrast there were no changes in arousal responses to hypercapnia during non-REM (NREM) sleep or to hypoxia in either NREM or REM sleep. However, during the assisted hypoxic runs, EMG activity of the transversus abdominis muscle was increased compared with the unassisted runs; therefore, the effects on arousal threshold of unloading the inspiratory muscles may have been offset by increased loading of the expiratory muscles. The findings indicate that even in the absence of added mechanical loads, mechanoreceptor stimuli probably arising in the respiratory muscles contribute to the arousal response to hypercapnia during REM sleep.
Asunto(s)
Nivel de Alerta/fisiología , Dióxido de Carbono/farmacología , Hipoxia/fisiopatología , Músculos Respiratorios/fisiología , Sueño/fisiología , Animales , Perros , Electromiografía , Retroalimentación/fisiología , Hipercapnia/fisiopatología , Mecanorreceptores/fisiología , Respiración Artificial , Sueño REM/fisiología , Nervio Vago/fisiologíaRESUMEN
The responses of the diaphragm, external oblique, and transversus abdominis muscles to hyperoxic hypercapnia and isocapnic hypoxia were studied in four awake dogs to test the hypothesis that central and peripheral chemoreceptor inputs result in different patterns of respiratory muscle activation. The dogs were trained to lie quietly in place, and electromyographic (EMG) discharges of the diaphragm (EMGdi), external oblique (EMGeo), and transversus abdominis (EMGta) were recorded from chronically implanted electrodes. Both hypercapnia and hypoxia recruited EMGeo and EMGta activity, but at comparable levels of minute volume of ventilation the EMG activity of the abdominal muscles was greater during hypercapnia than during hypoxia. However the two chemical stimuli also resulted in different tidal volume (VT) and respiratory frequency responses at any given minute volume of ventilation. When EMG activity was reanalyzed as a function of VT, EMGeo and EMGta were the same for a given VT whether induced by hypercapnia or hypoxia, but EMGdi was consistently greater during hypoxia than during hypercapnia. When the vagus nerves were blocked by cooling exteriorized cervical vagal loops, all abdominal muscle EMG activity was abolished. The findings support the concept that stimulation of the central and peripheral chemoreceptors results in asymmetric activation of the inspiratory and expiratory respiratory muscles. The findings also indicate that afferent vagal stimuli play an important facilitatory role in activation of the abdominal expiratory muscles.
Asunto(s)
Músculos Abdominales/fisiología , Respiración/fisiología , Músculos Respiratorios/fisiología , Músculos Abdominales/inervación , Animales , Dióxido de Carbono/sangre , Dióxido de Carbono/metabolismo , Células Quimiorreceptoras/fisiología , Diafragma/inervación , Diafragma/fisiología , Perros , Electromiografía , Hipoxia/fisiopatología , Neuronas Motoras/fisiología , Músculos Respiratorios/inervación , Volumen de Ventilación Pulmonar , Nervio Vago/fisiologíaRESUMEN
The role of respiratory mechanoreceptor stimuli in the arousal response to hypoxia was studied in three trained dogs. The dogs breathed through a cuffed endotracheal tube inserted through a chronic tracheostomy, and resistive loads of 8 to 49 cm H2O/L/s were added to the expiratory circuit. Arterial O2 saturation (SaO2) was measured with an ear oximeter, and isocapnic progressive hypoxia was induced by a rebreathing technique. Arousal from sleep was determined by electroencephalographic and behavioral criteria. SaO2 at arousal from non-rapid eye movement (NREM) sleep increased progressively from 67.5 +/- 4.6% (mean +/- SEM), with no added resistance to 85.2 +/- 0.5% with the highest resistance (p less than 0.01), and from 60.6 +/- 0.6 to 81.6 +/- 0.4% during REM sleep (p less than 0.01). The added resistances also increased the steady-state (normoxic) level of alveolar PCO2 (PACO2). However, when PACO2 was increased to comparable levels by the addition of dead space rather than expiratory resistance to the breathing circuit, SaO2 at arousal from hypoxia was significantly lower than during expiratory resistive loading (p less than 0.05). We therefore conclude that mechanoreceptor stimuli arising from the ventilatory apparatus may contribute substantially to the arousal response to hypoxia.
Asunto(s)
Nivel de Alerta/fisiología , Hipoxia/fisiopatología , Respiración/fisiología , Sueño/fisiología , Animales , Perros , Hipercapnia/fisiopatología , Oxígeno/sangre , Estimulación Física , Espacio Muerto Respiratorio , Estimulación Química , Trabajo RespiratorioRESUMEN
The present findings in awake and sleeping dogs confirm the early observations in anesthetized cats (Bainton et al., 1978; Sears et al., 1982), and more recent studies in awake and sleeping humans (Takasaki et al., 1989), that suggest an asymmetry in pattern of respiratory motoneuron and muscle activation by central and peripheral chemoreceptor stimulation, with central chemoreceptor stimulation driving both inspiratory and expiratory mechanisms, and peripheral chemoreceptor stimulation driving inspiratory and inhibiting expiratory mechanisms. Because REM sleep inhibits the nondiaphragmatic muscles, which include the expiratory muscles, there is a reduction in CO2 response during this sleep stage. In contrast because the response to hypoxia is mediated predominantly by the diaphragm, which is not generally inhibited by REM sleep, there is less effect of REM sleep on the overall response to hypoxia. In addition to being of basic importance, these concepts may have important clinical implications.
Asunto(s)
Dióxido de Carbono/fisiología , Células Quimiorreceptoras/fisiología , Respiración/fisiología , Músculos Respiratorios/inervación , Fases del Sueño/fisiología , Sueño REM/fisiología , Vigilia/fisiología , Vías Aferentes/fisiología , Animales , Diafragma/inervación , Perros , Electroencefalografía , Electromiografía , Neuronas Motoras/fisiología , Tono Muscular/fisiología , Oxígeno/fisiología , Centro Respiratorio/fisiología , Nervio Vago/fisiologíaRESUMEN
The mechanisms responsible for hypoventilation during rapid-eye-movement (REM) sleep in patients with diaphragmatic weakness are not clear. Therefore, we studied the effects of unilateral (UDP) and bilateral (BDP) diaphragmatic paralysis on ventilation during wakefulness (W), slow-wave sleep (SWS), and REM sleep. Studies were performed in 3 trained dogs in which small silicone cuffs had been implanted surgically around the phrenic nerves. Reversible diaphragmatic paralysis was induced during wakefulness or sleep by bathing the phrenic nerves in local anesthetic injected through a catheter attached to the phrenic cuffs. The UDP reduced abdominal expansion and increased rib cage expansion, but had no effect on minute volume of ventilation (VI) or end-tidal PCO2 (PACO2). The BDP produced marked abdominal paradox, but did not reduce VI during W or SWS and had no effect on tidal volume or respiratory frequency. In contrast, during REM sleep, VI was decreased by an average of 21% mainly because of a fall in tidal volume, and PACO2 increased by 2.4 mm Hg compared with that during the intact state. Furthermore, addition of extra dead space to the breathing circuit, which was well tolerated in intact dogs, led to a progressive increase in PACO2 during BDP and to arousal from sleep. The findings indicate that acute BDP does not impair ventilation during quiet W or SWS, but reduces ventilation during REM sleep, supporting the concept that during REM sleep maintenance of ventilation is critically dependent on diaphragmatic compensation for intercostal and accessory muscle inhibition.
Asunto(s)
Hipoventilación/etiología , Parálisis Respiratoria/fisiopatología , Sueño/fisiología , Vigilia/fisiología , Animales , Perros , Electroencefalografía , Hipoventilación/fisiopatología , Rendimiento Pulmonar , Nervio Frénico/fisiología , Intercambio Gaseoso Pulmonar , Músculos Respiratorios/fisiopatología , Parálisis Respiratoria/complicaciones , Sueño REM/fisiologíaRESUMEN
We examined the role of the upper airway in the regulation of the pattern of breathing in six adult dogs during wakefulness and sleep. The dogs breathed through a fenestrated endotracheal tube inserted through a tracheostomy. The tube was modified to allow airflow to be directed either through the nose or through the tracheostomy. When airflow was diverted from nose to tracheostomy there was an abrupt increase in the rate of expiratory airflow, resulting in prolongation of the end-expiratory pause but no change in overall expiratory duration or respiratory frequency. Furthermore, electromyogram recordings from implanted diaphragmatic and laryngeal muscle electrodes did not show any changes that could be interpreted as an attempt to delay expiratory airflow or increase end-expiratory lung volume. The effects of switching from nose to tracheostomy breathing could be reversed by adding a resistance to the endotracheal tube so as to approximate upper airway resistance. The findings indicate that under normal conditions in the adult dog upper airway receptors play little role in regulation of respiratory pattern and that the upper airway exerts little influence on the maintenance of end-expiratory lung volume.