RESUMEN

Arousals are often considered to be events which have an abrupt onset and offset, indicating abrupt changes in the state of the cortex. We hypothesized that cortical state, as reflected in electroencephalograph (EEG) signals, exhibits progressive systematic changes before and after a spontaneous, isolated arousal and that the time courses of the spectral components of the EEG before and after an arousal would differ between healthy middle-aged and elderly subjects. We analyzed the power spectrum and Sample Entropy of the C3A2 EEG before and after isolated arousals from 20 middle-aged (47.2±2.0 years) and 20 elderly (78.4±3.8 years) women using polysomnograms from the Sleep Heart Health Study database. In middle-aged women, all EEG spectral band powers <16 Hz exhibited a significant increase relative to baseline at some time in the 21 s before an arousal, but only low- (0.2-2.0 Hz) and high-frequency (2.0-4.0 Hz) delta increased in elderly and only during the last 7 s pre-arousal. Post-arousal, all frequency bands below 12 Hz transiently fell below pre-arousal baseline in both age groups. Consistent with these findings, Sample Entropy decreased steadily before an arousal, increased markedly during the arousal, and remained above pre-arousal baseline levels for ∼30 s after the arousal. In middle-aged, but not in elderly, women the presence of early pre-arousal low delta power was associated with shorter arousals. We propose that this attenuation of the effect of the arousing stimulus may be related to the slow (<1 Hz) cortical state oscillation, and that prolonged alterations of cortical state due to arousals may contribute to the poor correlation between indices of arousals and indices of sleepiness or impaired cognitive function.

Asunto(s)

RESUMEN

Analysis of respiratory muscle activity is a promising technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Evaluation of interactions between muscles is very useful in order to determine the muscular pattern during an exercise. These interactions have already been assessed by means of different linear techniques like cross-spectrum, magnitude squared coherence or cross-correlation. The aim of this work is to evaluate interactions between respiratory and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF), and finding out what information can be extracted from it. Some parameters are defined and calculated from CMIF between ventilatory and myographic signals of three respiratory muscles. Finally, differences in certain parameters were obtained between OSAS patients and healthy subjects indicating different respiratory muscle couplings.

RESUMEN

The correlation structure of breath-to-breath fluctuations of end-expiratory lung volume (EEV) was studied in anesthetized rats with intact airways subjected to positive and negative transrespiratory pressure (i.e., PTRP and NTRP, correspondingly). The Hurst exponent, H, was estimated from EEV fluctuations using modified dispersional analysis. We found that H for EEV was 0.5362 +/- 0.0763 and 0.6403 +/- 0.0561 with PTRP and NTRP, respectively (mean +/- SD). Both H were significantly different from those obtained after random shuffling of the original time series. Also, H with NTRP was significantly greater than that with PTRP (P = 0.029). We conclude that in rats breathing through the upper airway, a positive long-term correlation is present in EEV that is different between PTRP and NTRP.

Asunto(s)

RESUMEN

To test the possibility that the variations in end-expiratory lung volume (EEV) might exhibit long-term correlation, we calculated the Hurst exponent H for EEV in anesthetized rats during sustained positive and negative transrespiratory pressure (i.e., (PTRP) and (NTRP), correspondingly) using the dispersional analysis method. In nine vagi-intact rats, H for EEV was 0.551+/-0.051 (mean+/-std) and 0.641 +/-0.076 (mean+/-std) with PTRP and NTRP, respectively. In both cases H was significantly different from those obtained after random shuffling of the original time series, indicating a positive long-term correlation in EEV. Also H with NTRP was significantly greater than that with PTRP (P=0.015). In six vagotomized rats, there was no significant difference in H for EEV between NTRP and PTRP. We demonstrated that long-term correlation is present in EEV. We inferred that the stimulation of vagal afferents could change the fractal property in EEV since different vagal pulmonary receptors are activated by PTRP and NTRP. Although the exact mechanisms for the fractal behavior are unknown, the results suggest that interaction of the pulmonary mechanoreceptor activity with the central respiratory pattern generator might contribute to the observed long-term correlation.

Asunto(s)

RESUMEN

The effects of upper airway (UAW) flows and pressures on breathing pattern and respiratory muscle activities were studied in anesthetized rats breathing through a tracheostomy. A steady flow (approximately 1000 ml/kg/min) of cold dry air, or cold wet air, or warm wet air was passed through the UAW, in the expiratory direction for approximately 20 sec (20-40 sec). In other trials positive or negative pressure was applied to the isolated UAW for a similar duration. There was a marked prolongation of the expiratory duration and decreases in peak inspiratory flow, tidal volume, and peak diaphragm electromyogram (EMG) activity in response to cold dry airflow. The responses to cold wet air were reduced but still significant. Warm wet air had no effect on breathing. These responses show that UAW cooling and drying depress breathing in the rat and that cooling itself could cause the inhibition of breathing. Negative pressure induced substantial increases in genioglossus and laryngeal inspiratory activity while positive pressure caused a decrease in genioglossus activity. Positive pressure also increased expiratory time while negative pressure increased inspiratory time. These results confirm the functional role of the UAW dilating muscles in preventing UAW from collapse in rats.

Asunto(s)

RESUMEN

Because of the oscillatory pattern of upper airway resistance and breathing during sleep in patients with obstructive sleep apnea (OSA), we hypothesized that OSA patients have an underlying instability of ventilatory drive to inspiratory muscles. To assess the stability of ventilatory drive in OSA patients and controls, we used the pseudorandom binary stimulation (PRBS) test and examined the closed- and open-loop responses to hyperoxic hypercapnia. The closed-loop response is produced by interactions of dynamic gain in controller, plant, and ventilatory feedback. The open-loop response reflects controller dynamic gain or frequency-dependent chemosensitivity. As compared with 16 nonapneic, nonobese control subjects, a group of nine obese OSA patients had a higher peak response and a more rapid and irregular recovery phase of the closed-loop CO2 response in the PRBS test. The two groups had similar open-loop responses in the PRBS test, suggesting that central dynamic CO2 chemosensitivity was not abnormal in OSA. We conclude that the differences between OSA patients and controls in the closed-loop response in the PRBS test are not due to differences in dynamic controller gain, but are related to differences in dynamic plant gain and/or negative ventilatory feedback. In addition to OSA, obesity may affect these variables and may have been responsible for our findings.

Asunto(s)

Asunto(s)

RESUMEN

Modarreszadeh and Bruce (J. Appl. Physiol. 76: 2765-2775, 1994) proposed that continuous random disturbances in arterial PCO2 are more likely to elicit ventilatory oscillation patterns that mimic periodic breathing in normoxia than in hyperoxia. To test this hypothesis experimentally, in nine awake humans we applied pseudorandom binary inspired CO2 fraction stimulation in normoxia and hyperoxia to derive the closed-loop and open-loop ventilatory responses to a brief CO2 disturbance in terms of impulse responses and transfer functions. The closed-loop impulse response has a significantly higher peak value [0.143 +/- 0.071 vs. 0.079 +/- 0.034 (SD) l . min-1 . 0.01 l CO2-1, P = 0.014] and a significantly shorter 50% response duration (42.7 +/- 13.3 vs. 72.3 +/- 27.6 s, P = 0.020) in normoxia than in hyperoxia. Therefore, the ventilatory responses to transient CO2 disturbances are less damped (but generally not oscillatory) in normoxia than in hyperoxia. For the closed-loop transfer function, the gain in normoxia increased significantly (P < 0.0005), while phase delay decreased significantly (P < 0.0005). The gain increased by 108.5, 186.0, and 240.6%, while phase delay decreased by 26.0, 18.1, and 17.3%, at 0. 01, 0.03, and 0.05 Hz, respectively. Changes in the same direction were found for the open-loop system. Generally, an oscillatory ventilatory response to a small transient CO2 disturbance is unlikely during wakefulness. However, changes in parameters that lead to additional increases in chemoreflex loop gain are more likely to initiate oscillations in normoxia than in hyperoxia.

Asunto(s)

RESUMEN

In anesthetized rats, vagal afferent activities activate slow central mechanisms which modulate the pattern of breathing over several breaths, giving rise to increased breath to breath variability of respiratory pattern. We hypothesized that variability in breathing pattern would produce variability in blood gases and further enhance breath to breath variability of inspired ventilation. Anesthetized rats were placed in a head-out plethysmograph and spontaneous breathing recorded during inhalation of room air and 100% oxygen. The standard deviations and coefficients of variation of ventilation were similar for both inspired gases, but the shapes of the power spectra of ventilation differed, indicating a relative increase in low-frequency power on room air in those animals exhibiting little low-frequency power on oxygen. Simple indices of variability cannot discriminate these temporal changes in breathing pattern variability.

Asunto(s)

RESUMEN

In anesthetized, tracheotomized rats continuous negative airway pressure (CNAP) augments breath-to-breath variability of the respiratory pattern compared to that during continuous positive airway pressure (CPAP). To test the hypothesis that loss of airflow regulation by the upper airway was responsible for this increased variability during CNAP we measured respiratory pattern regularity in rats with intact airways subjected to steady inflating and deflating transrespiratory pressures. The coefficients of variation of tidal volume, peak inspiratory flow, and rate of change of flow at end-inspiration were larger during deflation maneuvers than during inflations, whereas the coefficients of variation of inspiratory and expiratory durations were not different. A variable degree of expiratory flow retardation often was observed during deflation. We conclude that breathing through the upper airway does not prevent the increase in variability of the respiratory pattern associated with deflation.

Asunto(s)

RESUMEN

The degree of ventilatory stability of human subjects is inferred from the presence or absence of oscillations in ventilation in response to a brief CO2 disturbance using the method of pseudorandom stimulation. Simultaneously, chemosensitivity is measured. Stability and chemosensitivity are compared in hyperoxia between wakefulness and stage 2 non-rapid eye movement (NREM) sleep and between normoxia and hyperoxia awake. Stability is unchanged between wakefulness and sleep but chemosensitivity decreases in sleep. In contrast, stability is reduced in normoxia whereas chemosensitivity is larger than in hyperoxia. It is concluded that chemosensitivity and ventilatory stability may change independently, implying that chemosensitivity alone is not an adequate indicator of the likelihood of a subject to exhibit periodic breathing.

Asunto(s)

RESUMEN

We used an isolated perfused lung preparation of the rabbit to study the effect of increasing blood flow on pulmonary capillary transit time by two methods. In one method, capillary transit time was measured from fluorescent dye dilution curves from arterioles and venules of the subpleural microcirculation. Values of transit time were similar to those for the whole lung determined by dividing capillary blood volume by blood flow. Capillary transit times averaged 0.50-0.62 sec at a control blood flow of 80 ml min-1 kg-1 and decreased to 0.14-0.18 sec as blood flow increased to 6 times control. To determine whether the reduced transit time would limit O2 transport, we studied the effect of blood flow on oxygenation. Two isolated rabbit lungs were perfused in series. Blood from one lung deoxygenated by ventilation with a N2-CO2 mixture was oxygenated by the test lung ventilated with air. Ventilation was matched to blood flow. PO2 and PCO2 were measured in blood flowing into and out of the test lung. At all flows, no significant alveolar gas-to-end-capillary blood PO2 gradient (A-aDO2) was measured. The isolated perfused rabbit lung showed no transit time limitation to oxygenation for blood flows that are consistent with heavy exercise in vivo.

Asunto(s)

RESUMEN

We studied the effects of changes in the level of ventilation on respiratory discomfort during isocapnic exercise. Six subjects exercised at 60 W on a cycle ergometer. They initially breathed 2.5% CO2 in oxygen for 75 breaths. Ventilatory parameters of the last 10 breaths were used as controls. In 7 subsequent test sessions each lasting 2 min alternating with 2 min free breathing periods, subjects tried to achieve a target ventilation ranging from 0.7 to 1.3 times the control with a visual feedback system. End-tidal CO2 was regulated automatically at the control level by changing the inspired CO2. Breathing discomfort was measured at the end of each session using a visual analog scale. Isocapnic constraining of ventilation (0.7 times the control) during exercise significantly increased respiratory discomfort (p < 0.05). Increases in ventilation had no significant effect. These results indicate that respiratory discomfort during exercise is exaggerated when the level of ventilation falls below that spontaneously adopted even when chemical drives are held constant.

Asunto(s)

RESUMEN

Breath-to-breath variations in the pattern of breathing can occur as uncorrelated random variations ("white noise"), correlated random changes, or as one of two types of nonrandom variations: periodic oscillations or nonrandom nonperiodic fluctuations. White noise is probably present in all physiological processes. In many cases, periodic variations are due to oscillations originating in chemoreflex feedback loops. It has long been hypothesized that correlated random variations in breathing pattern are due to central neutral "memory" mechanisms, but part of this behavior might be due to chemoreflex mechanisms. Recently it has been concluded that nonlinear interactions between pulmonary and airway afferent activities and integrative central respiratory mechanisms can produce nonrandom nonperiodic (and also periodic) variability of the respiratory pattern. These latter studies have provided new insights about the behavioral relevance of the integrative character of central respiratory mechanisms and the time-varying nature of pulmonary afferent activities and have emphasized the importance of identifying the physiological bases for these phenomena. These and other findings are interpreted assuming that respiratory rhythm generation/pattern formation occurs via a nonlinear oscillator, and novel inferences concerning temporal variations of the breathing pattern are proposed.

Asunto(s)

RESUMEN

Oscillatory ventilatory pattern occurs more frequently in sleep despite the stabilizing factor of sleep-induced reduction in CO2 chemosensitivity. In nine young normal humans, we have tested the hypothesis that, despite a sleep-induced reduction in chemosensitivity, the transient central chemoreceptor-mediated change inspiratory ventilation (VI) caused by a standardized disturbance to chemoreflex ventilatory control is similar in quiet sleep and wakefulness. The equivalent VI response to a single-breath hyperoxic hypercapnic stimulus (i.e., inhaling a single breath of 0.01 liter of CO2 in O2--a direct measure of "closed-loop" dynamic response) was determined using pseudorandom binary CO2 stimulation and the prediction-error method of transfer function estimation. From these data, the response of VI to a single-breath increase of 1 Torr in end-tidal PCO2 was also derived, from which "dynamic" central chemosensitivity was calculated. Despite a 43% reduction in dynamic central chemosensitivity, the peak and the area under the closed-loop VI response are similar in wakefulness and quiet sleep, whereas sleep increases the duration of the response by 48%. Thus hyperoxic ventilatory stability is not reduced in quiet sleep relative to wakefulness. We propose that changes in dynamics of pulmonary gas exchange in sleep substantially offset the decreased chemosensitivity, thereby maintaining the gains and time constants of the central chemoreceptor-mediated component of the closed-loop ventilatory control system similar to those during wakefulness.

Asunto(s)

RESUMEN

Using experimental and simulation studies, we assessed the applicability of pseudorandom binary hypoxic stimulation (PRBS) for estimating the dynamic respiratory response to a single breath of hypoxia. In experimental studies on rats we tested whether the transient ventilatory response to hypoxia based on the PRBS technique converges to the measured response to a true single breath of hypoxia. Plethysmographic volume recordings were obtained from 7 urethane anesthetized, bilaterally vagotomized rats while the inspired O2 level was switched pseudorandomly between 21% and 12%. The psuedorandom estimates were comparable to the ensemble averaged responses to 15-40 trials of a single-breath inspiration of 12% O2. Ventilation peaked in 2-3 breaths and the response lasted for 15-20 breaths and was primarily due to a decrease in breath duration. Changes in CO2 concentration in the blood cause an underestimate of the purely hypoxic transient response. In simulation studies we also demonstrated the applicability of this technique to human subjects using a mathematical model of human respiratory control. We conclude that the pseudorandom technique will provide a very good estimate of the ventilatory dynamics to inhalation of a single breath of hypoxic gas in rats and humans.

Asunto(s)

RESUMEN

We investigated the effects of voluntary control of breathing on autonomic function in cardiovascular regulation. Variability in heart rate was compared between 5 min of spontaneous and controlled breathing. During controlled breathing, for 5 min, subjects voluntarily reproduced their own spontaneous breathing pattern (both rate and volume on a breath-by-breath basis). With the use of this experimental design, we could unmask the effects of voluntary override of the spontaneous respiratory pattern generator on autonomic function in cardiovascular regulation without the confounding effects of altered respiratory pattern. Results from 10 subjects showed that during voluntary control of breathing, mean values of heart rate and blood pressure increased, whereas fractal and spectral powers in heart rate in the respiratory frequency region decreased. End-tidal PCO2 was similar during spontaneous and controlled breathing. These results indicate that the act of voluntary control of breathing decreases the influence of the vagal component, which is the principal parasympathetic influence in cardiovascular regulation.

Asunto(s)

RESUMEN

Variations in respiratory pattern influence the heart rate spectrum. It has been suggested, hence, that metronomic respiration should be used to correctly assess vagal modulation of heart rate by using spectral analysis. On the other hand, breathing to a metronome has been reported to increase heart rate spectral power in the high- or respiratory frequency region; this finding has led to the suggestion that metronomic respiration enhances vagal tone or alters vagal modulation of heart rate. To investigate whether metronomic breathing complicates the interpretation of heart rate spectra by altering vagal modulation, we recorded the electrocardiogram and respiration from eight volunteers during three breathing trials of 10 min each: 1) spontaneous breathing (mean rate of 14.4 breaths/min); 2) breathing to a metronome at the rate of 15, 18, and 21 breaths/min for 2, 6, and 2 min, respectively; and 3) breathing to a metronome at the rate of 18 breaths/min for 10 min. Data were also collected from eight volunteers who breathed spontaneously for 20 min and breathed metronomically at each subject's mean spontaneous breathing frequency for 20 min. Results from the three 10-min breathing trials showed that heart rate power in the respiratory frequency region was smaller during metronomic breathing than during spontaneous breathing. This decrease could be explained fully by the higher breathing frequencies used during trials 2 and 3 of metronomic breathing. When the subjects breathed metronomically at each subject's mean breathing frequency, the heart rate powers during metronomic breathing were similar to those during spontaneous breathing. Our results suggest that vagal modulation of heart rate is not altered and vagal tone is not enhanced during metronomic breathing.

Asunto(s)

RESUMEN

We tested the hypothesis that breath-to-breath variations in arterial CO2 partial pressure (PaCO2) during spontaneous breathing of awake humans cause a significant portion of spontaneous ventilatory variability (including periodic oscillations). This hypothesis was tested in two ways. First, using a recently developed adaptive PaCO2 buffering technique we reduced the spontaneous variability in PaCO2 of six awake normal young human subjects during hyperoxia and observed a corresponding decrease in their breath-to-breath ventilatory variations. Second, we predicted the ventilatory responses to CO2 disturbances by using a model of chemical control of ventilation, both examining the hyperoxic condition (similar to experimental studies) and predicting the responses to CO2 variations of a normal subject breathing room air. In all experimental and theoretical studies, we found that small random disturbances to PaCO2 have significant effects on ventilation, including the potential for such PaCO2 disturbances to elicit oscillatory fluctuations in ventilation even though the ventilatory chemical control system was stable (i.e., a brief disturbance to PaCO2 did not elicit sustained ventilatory oscillations). On the basis of these results we propose that the stability of chemoreflex ventilatory control loops depends on both "loop gain" factors and the characteristics of random disturbances to PaCO2.

Asunto(s)

RESUMEN

We have designed and implemented a computer-controlled system that uses an adaptive control algorithm (generalized minimum variance) to buffer the breath-by-breath variations of the end-tidal CO2 fraction (FETCO2) that occur spontaneously or are exaggerated in certain experimental protocols (e.g., induced hypoxia, any type of induced variations in the ventilatory pattern). Near the end of each breath, FETCO2 of the following breath is predicted and the inspired CO2 fraction (FICO2) of the upcoming breath is adjusted to minimize the difference between the predicted and desired FETCO2 of the next breath. The one-breath-ahead prediction of FETCO2 is based on an adaptive autoregressive with exogenous inputs (ARX) model: FETCO2 of a given breath is related to FICO2, FETCO2 of the previous breath, and inspiratory ventilation. Adequacy of the prediction is demonstrated using data from experiments in which FICO2 was varied pseudorandomly in wakefulness and sleep. The algorithm for optimally buffering changes in FETCO2 is based on the coefficients of the ARX model. We have determined experimentally the frequency of FETCO2 variations that can be buffered adequately by our controller, testing both spontaneous variations in FETCO2 and variations induced by hypoxia in young awake human subjects. The controller is most effective in buffering variations of FETCO2 in the frequency range of <0.1 cycle/breath. Some potential applications are discussed.

Asunto(s)