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Biomedical subjects

M C Khoo

Publications and source records attributed to M C Khoo.

At least 19 recordsLinked to original sources
PubMed2001

Cardiac autonomic control in obstructive sleep apnea: effects of long-term CPAP therapy.

To determine how long-term treatment with continuous positive airway pressure (CPAP) affects cardiac autonomic function, we measured R-R interval (RRI), respiration, and blood pressure in 13 awake patients with moderate-to-severe obstructive sleep apnea (OSA) in both supine and standing postures, before and after 3 to 9 mo of home therapy. Using visual feedback, the subjects controlled their respiration to track a randomized breathing pattern. From the RRI spectrum, we computed high-frequency power and the ratio of low-frequency to high-frequency power (LHR). To correct for differences in breathing, the average transfer gain relating respiration to RRI changes (G(RSA)) and the modified low-frequency to high-frequency ratio (MLHR) were also derived. CPAP therapy did not change the conventional spectral indices of heart rate variability (HRV). However, G(RSA) increased with average nightly CPAP use in supine (p < 0.01) and standing (p < 0.03) postures, whereas MLHR decreased with CPAP compliance during standing (p < 0.03). Supine mean heart rate decreased with compliance (p < 0.03). None of the estimated parameters was correlated with duration of therapy when actual CPAP use was not taken into account. These results suggest that CPAP treatment improves vagal heart rate control in patients with OSA and that the degree of improvement varies directly with compliance level.

Adult↗
PubMed2001

Spectral analysis of heart rate variability and respiration during sleep in cocaine-exposed neonates.

This study's objective was to examine the autonomic control of heart rate and respiration during the neonatal period in human infants with prenatal exposure to cocaine. Four-hour daytime recordings of the electrocardiogram (ECG) were obtained from 15 cocaine-exposed and 13 non-exposed full-term neonates at 2 weeks of age during quiet sleep (QS) and active sleep (AS). For each 1-min epoch of sleep, the power spectrum of the R-R intervals was computed from the ECG to obtain the total power (0-2 Hz), and spectral power in the high-frequency (HFP, 0.3-2 Hz), mid-frequency (MFP, 0.1-0.2 Hz), and low-frequency (LFP, 0.03-0.1 Hz) bands. Respiration was also monitored and processed using similar spectral analysis procedures. Cocaine-exposed neonates showed enhanced heart rate variability reflected by an increase in spectral power across all frequency bands. Spectral power in LFP and MFP was higher in cocaine-exposed neonates during both sleep states, but only in HFP during QS. There were no respiratory patterning differences between the groups to account for these findings. The index of sympathovagal balance (LFP + MFP)/HFP, showed no differences between the groups. We conclude that infants exposed to cocaine in utero show differences in the modulation of heart rate reflecting an increase in both vagal and sympathetic influences.

Autonomic Nervous System↗
PubMed2001

Nonlinear dynamics of heart rate variability in cocaine-exposed neonates during sleep.

The aim of this study was to determine the effects of prenatal cocaine exposure (PCE) on the dynamics of heart rate variability in full-term neonates during sleep. R-R interval (RRI) time series from 9 infants with PCE and 12 controls during periods of stable quiet sleep and active sleep were analyzed using autoregressive modeling and nonlinear dynamics. There were no differences between the two groups in spectral power distribution, approximate entropy, correlation dimension, and nonlinear predictability. However, application of surrogate data analysis to these measures revealed a significant degree of nonlinear RRI dynamics in all subjects. A parametric model, consisting of a nonlinear delayed-feedback system with stochastic noise as the perturbing input, was employed to estimate the relative contributions of linear and nonlinear deterministic dynamics in the data. Both infant groups showed similar proportional contributions in linear, nonlinear, and stochastic dynamics. However, approximate entropy, correlation dimension, and nonlinear prediction error were all decreased in active versus quiet sleep; in addition, the parametric model revealed a doubling of the linear component and a halving of the nonlinear contribution to overall heart rate variability. Spectral analysis indicated a shift in relative power toward lower frequencies. We conclude that 1) RRI dynamics in infants with PCE and normal controls are similar; and 2) in both groups, sympathetic dominance during active sleep produces primarily periodic low-frequency oscillations in RRI, whereas in quiet sleep vagal modulation leads to RRI fluctuations that are broadband and dynamically more complex.

Cocaine↗
PubMed2000

Determinants of ventilatory instability and variability.

This paper reviews the major mechanisms that can give rise to various forms of variability in the ventilatory pattern. First, an elevated controller gain, coupled with the presence of delays and response lags in the chemoreflex loops, can lead to instability in feedback control and give rise to periodic breathing. This form of ventilatory stability can be assessed quantitatively by employing the concept of 'loop gain'. Several different methods of estimating loop gain from steady state or dynamic respiratory measurements are discussed. An inherently stable respiratory control system can also exhibit periodic behavior due to the influence of primary fluctuations in sleep-wake state and other physiological variables, such as cardiac output and cerebral blood flow. Self-sustained, irregular ventilatory fluctuations may be generated by nonlinear dynamic interactions between various components of the respiratory control system, such as the lung vagal afferents and the respiratory pattern generator, or through the propagation of stochastic disturbances around the chemoreflex loops.

Algorithms↗
PubMed1999

Spectral indices of cardiac autonomic function in obstructive sleep apnea.

Spectral analysis of heart rate variability (HRV) is useful as a noninvasive means of assessing autonomic function in patients with obstructive sleep apnea (OSA). However, standard spectral measures, such as the ratio of low-frequency to high-frequency power (LHR) and normalized high-frequency power (NHFP), can be confounded by the abnormal breathing patterns that occur during sleep. To circumvent this limitation, we employed an autoregressive modeling approach to partition the RR time-series into a component that is correlated with respiration and a respiration-independent component. From these components, we derived two new spectral indices: the modified LHR (MLHR) and the average gain relating respiration to RR changes (GRSA). Six normals and seven OSA patients were studied in relaxed wakefulness and stage 2 sleep; during sleep, the OSA patients were studied without and with continuous positive airway pressure (CPAP) therapy. All four spectral indices showed significant differences between OSA patients and normals in both wakefulness and sleep, although the changes in MLHR and GRSA were substantially larger and less variable: MLHR (p < 0.0003) and GRSA (p < 0.0001) vs. LHR (p < 0.005) and NHFP (p < 0.004). However, in the OSA subjects, LHR and NHFP were unchanged by CPAP. By contrast, CPAP produced a highly significant increase in GRSA (p < 0.0004), as well as a decrease in MLHR (p < 0.03). Thus, by compensating for the effects of breathing pattern differences, MLHR and GRSA unmasked the effects of CPAP therapy, which has been shown in previous studies to reduce sympathetic activity and increase vagal cardiac modulation.

Adult↗
PubMed1998

Fuzzy assessment of sleep-disordered breathing during continuous positive airway pressure therapy.

We propose a new method of quantifying sleep-disordered breathing (SDB) for the purpose of automating continuous positive airway pressure (CPAP) titration. Our algorithm, based on fuzzy logic, emulates the less-than-crisp kind of decision-making generally employed at the human level. Three input variables were first derived on a breath-by-breath basis from respiratory airflow measurements. These were: (1) the relative duration of inspiratory flow limitation in each breath; (2) the degree of hypopnea relative to the past 15 breaths; and (3) the intensity of snoring. Using these descriptors as inputs, our fuzzy inference algorithm produced a "severity index" (SI) quantifying the degree of SDB. Severity index was determined in CPAP titration procedures conducted on one normal snorer and 12 patients with moderate-to-severe obstructive sleep apnea. SI computed over the last 6 minutes of each CPAP level was compared against other more-conventional indices of SDB, such as total pulmonary resistance (RL), the number of apneas and hypopneas (NAH), and the number of arousals (NAr). In all but one of the subjects, the correlation coefficients for SI vs each of RL, NAH, and NAr were significantly different from zero, but not different from each other. The group correlation coefficients for SI vs RL, NAH, and NAr were 0.89, 0.86, and 0.87, respectively, demonstrating that SI accurately quantifies SDB. SI collapses multiple features of the airflow pattern into a single index and, therefore, may be useful as a "feedback" variable for the automatic control of CPAP therapy.

Adult↗
PubMed1998

Ventilatory dynamics of transient arousal in patients with obstructive sleep apnea.

The hyperpnea that accompanies arousal at the end of obstructive apnea is believed to be due to the progressive build-up in chemical drive during the apnea and a state-related decrease in upper airway resistance. We postulated the existence of a third component: a state-related transient increase in neural drive to the ventilatory pump muscles. To quantify this contribution, we measured the ventilatory response to arousal (VRA) in eight patients with obstructive sleep apnea (OSA) during continuous positive airway pressure (CPAP) therapy, applied at individually titrated levels. CPAP application reduced total pulmonary resistance (RL) to approximately normal levels, stabilizing ventilation and sleep state. Transient arousal from stage 2 sleep was induced using 5-sec tones (60-90 dB). Mean inspiratory flow increased above control on the second and third post-arousal breaths (P < 0.05), with a peak increase of 7.8 +/- 2.9 L/min while the accompanying changes in RL were significant. The time-course of VRA measured in three normal subjects under CPAP was similar to that observed in the OSA patients. However, elimination of CPAP prolonged the VRA time-course. Taken together, these findings demonstrate that: (1) during arousal, the increase in state-related neural respiratory drive is short-lived but not substantial; and (2) the resulting VRA time-course is shaped by the dynamics of the upper airway response to arousal.

Acoustic Stimulation↗
PubMed1998

Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea.

We studied the within-night variability of the maximum esophageal pressure deflection before apnea termination (DPmax) in nine patients with severe obstructive sleep apnea as an index of the arousal threshold and the mean electroencephalogram (EEG) delta power for each 30 s as an index of the timing of sleep cycles. Periodicity in the time variation of delta power and DPmax was analyzed by determining their power spectral density and their relationship determined by cross correlation. DPmax and delta power varied cyclically and in phase with a major periodicity (major peak in power spectral density) of 117.6 +/- 8.8 (SE) min. The correlation between the values of DPmax and delta power was significant (P < 0.001) in each subject (mean r = 0.47 +/- 0.03), and the coherence between DPmax and delta power at their dominant frequency was high. Within cycles of non-rapid-eye-movement sleep, DPmax and delta power increased, reaching peak values on average at or after midcycle. These findings suggest that the arousal threshold to airway occlusion in patients with obstructive sleep apnea varies cyclically during the night synchronous to the underlying cycles of sleep.

Activity Cycles↗
PubMed1997

Estimation of chemoreflex loop gain using pseudorandom binary CO2 stimulation.

We have developed a method for deriving estimates of the chemoreflex control loop gain (LG) from the ventilatory response to inhaled CO2, modulated between 0% and 5% in the form of a pseudorandom binary sequence. The corresponding changes in alveolar (and thus, arterial) CO2 result from two components: 1) the direct effect of breath-to-breath changes in inhaled CO2 and 2) the chemoreflex-mediated changes in ventilation. LG between 0.01 and 0.03 Hz, the frequency range pertinent to periodic breathing, was estimated by computationally delineating the first component from the overall ventilatory response. The method was tested against simulated and experimental data. In both cases, we found strong correlations between our predictions and LG magnitude estimates derived by other methods. However, LG phase estimates were considerably more variable when compared to model predictions based on small-signal analysis. We propose that our method, which uses data from a single test procedure lasting < 10 min, may be more useful than traditional tests of chemoresponsiveness for the quantitative assessment of respiratory control stability during changes in sleep-wake state.

Carbon Dioxide↗
PubMed1997

Estimation of cardiorespiratory transfer under spontaneous breathing conditions: a theoretical study.

Using simulated noisy sequences of respiration and heart rate, we assessed the accuracy of the respiratory sinus arrhythmia transfer function (RSATF) estimation under three kinds of spontaneous breathing patterns: regular or tidal breathing, periodic breathing with apnea, and broadband breathing. Estimation employing the cross-power and autopower spectra of the simulated data produced RSATF estimates that were generally more variable than those computed with an autoregressive modeling approach. Variability and bias errors in the RSATF estimates became larger as respiratory bandwidth decreased when the breathing pattern changed from broadband to periodic to regular breathing. However, between frequencies of 0.1 and 0.3 Hz, these errors fell within 12% in all breathing patterns. Error in the RSATF estimates was only slightly increased, with reductions in data length to as low as 90 s. The results suggest the feasibility of obtaining accurate estimates of RSATF between 0.1 and 0.8 Hz from a wide variety of conditions, such as in different sleep-wake states where voluntary control of breathing is not possible and the ventilatory pattern may vary substantially.

Arrhythmia, Sinus↗
PubMed1996

Dynamics of periodic breathing and arousal during sleep at extreme altitude.

To determine whether nocturnal periodic breathing (PB) at altitude is due primarily to unstable control of ventilation or the inability to maintain stable sleep states, we performed visual and computer analyses of the electroencephalographic and respiratory records of healthy volunteers at simulated altitudes of 4572, 6100 and 7620 m. Transient arousals were associated with < 52% of the apneas identified; thus, the PB cycle was not always associated with transient arousal. Following the termination of oxygen breathing, the reinitiation of PB was not dependent on the occurrence of arousal as the primary event. The transition from apnea to breathing preceded the appearance of arousal by approximately 1 to 4 sec. Ventilatory drive in the breaths immediately following arousal was significantly larger than corresponding control breaths, matched for SaO2. Our findings suggest that altitude-induced PB is unlikely to result from primary fluctuations in state. Arousals promote the development of PB with apnea and help to sustain these episodes, but are not necessary for their initiation.

Altitude↗
PubMed1996

Transduction dynamics of intrapulmonary CO2 receptors.

We have developed a functional model for quantitatively characterizing the transduction dynamics of the intrapulmonary CO2 receptors (IPC) in the snake lung. The model was based on experiments in which the neural discharges of several IPCs were recorded in response to abrupt step changes in CO2 concentration. Initial attempts to model the transduction dynamics linearly proved inadequate, although the linear model captured gross features such as rate sensitivity and the existence of two time constants in the adaptation time-course. However, with the incorporation of two static nonlinear features, namely, thresholding and preferential directionality of the rate-sensitive component, it was possible to account for over 80% of the total variation in the data. The model produced accurate predictions of IPC responses to other inputs, such as pseudorandom binary changes in CO2. The model also allows the prediction of IPC discharge in spontaneous breathing given measurements of lung CO2 concentration, and may serve as a starting point for further studies of transduction mechanisms at the cellular level.

Animals↗
PubMed1996

Modeling the interaction between arousal and chemical drive in sleep-disordered breathing.

We have measured the ventilatory response to acoustically induced arousal in normal subjects and patients with obstructive sleep apnea syndrome (OSAS). The arousal responses are similar in magnitude and time-course over the first 3 breaths, but in OSAS the subsequent response declines much more rapidly. Incorporation of these empirical findings into an existing model of sleep-disordered breathing allows an improved characterization of state-chemoreflex interactions. The shorter time-course of the arousal response in OSAS promotes greater ventilatory and state instability at low-to-intermediate levels of CO2 gain.

Adolescent↗
PubMed1996

Ventilatory dynamics during transient arousal from NREM sleep: implications for respiratory control stability.

The polysomnographic and ventilatory patterns of nine normal adults were measured during non-rapid-eye-movement (NREM) stage 2 sleep before and after repeated administrations of a tone (40-72 dB) lasting 5 s. The ventilatory response to arousal (VRA) was determined in data sections showing electrocortical arousal following the start of the tone. Mean inspiratory flow and tidal volume increased significantly above control levels in the first seven breaths after the start of arousal, with peak increases (64.2% > control) occurring on the second breath. Breath-to-breath occlusion pressure 100 ms after the start of inspiration showed significant increases only on the second and third postarousal breaths, whereas upper airway resistance declined immediately and remained below control for > or = 7 consecutive breaths. These results suggest that the first breath and latter portion of the VRA are determined more by upper airway dynamics than by changes in the neural drive to breathe. Computer model simulations comparing different VRA time courses show that sustained periodic apnea is more likely to occur when the fall in the postarousal increase in ventilation is more abrupt.

Adult↗