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Biomedical subjects

D W Carley

Publications and source records attributed to D W Carley.

At least 37 records · Page 2Linked to original sources
PubMed1996

Hydralazine reduces elevated sleep apnea index in spontaneously hypertensive (SHR) rats to equivalence with normotensive Wistar-Kyoto rats.

The effects of lowering blood pressure (BP) by hydralazine (HY) (2 mg/kg) on spontaneous (SA) and post-sigh (PSA) sleep apneas have been studied in spontaneously hypertensive (SHR) rats by monitoring their respiration and sleep by the EEG for 6 hours. Normotensive Wistar-Kyoto (WKY) rats, from which the SHR rat strain was derived, were used as an appropriate control. The SHR rats had more SA (p < 0.02) and PSA (p < 0.0001) apneas/hour than WKY rats during nonrapid eye movement sleep and their mean BP was higher by 40 mm Hg (p < 0.0001) than WKY rats. Administration of HY to SHR rats equalized their BP with the arterial pressure of WKY rats and reduced the SA and the PSA apneas/hour to equivalence with WKY normotensive rats. These results demonstrate that even in the context of lifelong hypertension, acute normalization of BP significantly reduces sleep apneas in rats. They further suggest that improved management of BP may be clinical benefit to patients with apnea who have long-standing hypertension.

Animals↗
PubMed1996

Respiratory and electrocortical responses to acoustic stimulation.

Although sleep-related obstructive apnea is most often associated with transient arousal, the impact of this arousal on respiratory control remains unclear. We employed binaural tone bursts (.5 second duration) to elicit repetitive transient arousals from sleep during polygraphic recordings in 5 adult volunteers. By this method, we elicited repetitive transient arousals with a mean duration of approximately 10 seconds from all stages of sleep. With respect to the 3 pre-stimulus breaths, acoustic stimulation was associated with increased tidal volume and decreased inspiratory duration for at least 4 breaths. These respiratory responses to acoustic stimulation were not significantly influenced by either presence of transient arousal from sleep or the sleep state from which arousal occurred. We conclude that transient electro-cortical state changes may be repeatedly evoked from all sleep stages by transient acoustic stimulation in normal sleepers. This sensory stimulation represents a significant respiratory stimulus even when generalized arousal from sleep does not occur.

Acoustic Stimulation↗
PubMed1996

Effects of inspired gas on sleep-related apnea in the rat.

Central apneas have been reported to occur in the rat during all stages of sleep. Two types of apnea have been described: spontaneous and postsigh, which are immediately preceded by an augmented breath. We studied the effect of inspired gas on the number and type of apneas in nine adult male Sprague-Dawley rats that were surgically prepared with cortical electroencephalogram and nuchal electromyogram electrodes. In addition to the electroencephalogram and electromyogram, we recorded respiration by the barometric method by using a single-chamber plethysmograph. Each rat was recorded from 1000 until 1600 on 4 separate days by using different inspired gases: room air, 100% O2, 15% O2, and 5% CO2. We found that the sleep-related apnea index was significantly higher during 100% O2 compared with room air (P < 0.05) and was significantly lower during 15% O2 and 5% CO2 compared with room air (P < 0.05). Postsigh apneas occurred more frequently than did spontaneous apneas (P < 0.0001). The coupling between sighs and apneas was strengthened by hyperoxia and weakened by hypoxia and hypercapnia (P < 0.05 for each). We conclude that stimulation of chemoreceptors acts to oppose apnea in the rat.

Animals↗
PubMed1995

Adenosine analogues modulate the incidence of sleep apneas in rats.

The effects of adenosine A1 and A2 agonists on spontaneous central sleep apneas in rats have been examined by simultaneously monitoring sleep and respiration in freely moving unanesthetized animals. Intraperitoneal administration of 1.0 mg/kg of the A1 receptor agonist R(-)N6-L-(2-phenyl-isopropyl)adenosine (L-PIA) and 150 and 300 micrograms/kg of 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adenosine hydrochloride (CGS 21680), a selective A2 agonist, decreased the apnea index (AI) during sleep. Within a sleep period, AI increased over time in both control and drug-treated animals. For both agonists, doses effective in reducing AI also significantly reduced sleep efficiency.

Adenosine↗
PubMed1995

Effect of induced transient arousal on obstructive apnea duration.

Six untreated male patients (age 19-55 yr) with obstructive sleep apnea underwent nocturnal polysomnography with acoustic stimulation to determine the effect of transient arousal on obstructive apneas during sleep. Binaural tone bursts (25-95 dB) were delivered in late expiration during the second obstructive apnea of a cycle consisting of four consecutive apneas. For the group, stimulated apneas were significantly shorter (P < 0.05, Fisher's protected least significant difference test) than were the unstimulated apneas when transient electrocortical arousal was elicited in both non-rapid-eye-movement (non-REM) sleep [mean 17 +/- 7 (SD) vs. 26 +/- 9, 23 +/- 10, and 26 +/- 12 s for 2nd vs. 1st, 3rd, and 4th apnea, respectively, of each cycle] and REM sleep (mean 19 +/- 10 vs. 35 +/- 15, 45 +/- 18, and 39 +/- 20 s). Without electrocortical arousal, the stimulated apnea was significantly shortened in non-REM (23 +/- 9 vs. 25 +/- 7, 24 +/- 8, and 26 +/- 8 s) but not in REM (32 +/- 16 vs. 37 +/- 12, 32 +/- 15, and 30 +/- 16 s). Tones delivered relatively early and late in the apnea were equally likely to be associated with resolution of the apnea. The nadir of arterial oxygen saturation of hemoglobin was inversely proportional to apnea length, with higher saturation nadirs associated with the stimulated apneas. These data indicate that transient arousal, induced by nonrespiratory stimulation, influences the resolution of obstructive apneas during sleep.

Acoustic Stimulation↗
PubMed1995

Palatal muscle electromyogram activity in obstructive sleep apnea.

Eight subjects (5 men, 3 women, ages 27 to 55) with obstructive sleep apnea syndrome (OSAS) were studied to quantify and compare electromyographic (EMG) activity of levator veli palatini (LVP) and palatoglossus (PG), two velopharyngeal muscles, and genioglossus (GG) during obstructive apnea cycles in non-rapid eye movement (NREM) sleep. EMG activity of three successive preapneic breaths, first and last apneic efforts, and three successive postapneic breaths was quantified for each muscle as peak phasic inspiratory EMG normalized as percent activity of the last preapneic breath. In all subjects, apnea onset coincided with simultaneous inspiratory EMG nadir of all three muscles (LVP = 63 +/- 40%, PG = 74 +/- 53%. GG = 83 +/- 48%. mean +/- SD activity of last preapneic breath). Apnea resolution did not occur until inspiratory EMG of all three muscles simultaneously reached maximal activity, at levels significantly greater than preapneic activity as well as activity of the last preapneic effort (LVP = 215 +/- 205%, PG = 227 +/- 240+, GG = 235 +/- 202%, mean +/- SD activity of last preapneic breath, p < 0.05, Fisher's partial least-squares difference [PLSD] test for each muscle). The presence or absence of electroencephalographic arousal at apnea resolution did not influence these patterns of EMG activity. Inspiratory recruitment of velopharyngeal as well as oropharyngeal muscles appears to be associated with upper airway patency during sleep in patients with OSAS.

Adult↗
PubMed1994

Acoustically induced cortical arousal increases phasic pharyngeal muscle and diaphragmatic EMG in NREM sleep.

Six healthy subjects (3 males, 3 females) were studied to assess phasic inspiratory responses of upper airway (UA) and diaphragm muscles to electrocortical arousal independent of other potential respiratory stimulation. Transient electroencephalographic (EEG) arousal (abrupt EEG frequency shift > or = 3 s without awakening) was induced during supine stage 2 non-rapid-eye-movement (NREM) sleep with binaural tone bursts (0.5 s, 4 kHz, 25-95 dB). Electromyograms (EMG) of levator veli palatini (EMGlvp) and genioglossus (EMGgg) were obtained with intramuscular electrodes, and EMG of diaphragm (EMGdi) was obtained with esophageal electrodes. EMG signals were processed as moving time-averaged inspiratory activity over 100-ms windows. For each arousal, each of five consecutive postarousal breaths (R1-R5) was scored for peak inspiratory phasic EMG and normalized as percent averaged EMG of the three prearousal breaths for all muscles. After arousal, EMGlvp was increased for R1-R5 and EMGgg and EMGdi were increased for R1-R4. The increase in EMGlvp was greater than those of EMGgg and EMGdi for all response breaths. There was a significant increase in EMGlvp in all subjects, and EMGgg and EMGdi were significantly increased in three and two subjects, respectively. These data indicate that isolated transient electrocortical arousal is generally associated with phasic inspiratory recruitment of UA and diaphragm muscles in normal humans during NREM sleep; velopharyngeal muscle recruitment appears to be more consistent and of greater magnitude and duration than that of oropharyngeal muscle or diaphragm. We speculate that transient arousal from sleep may contribute to UA patency independent of chemical and mechanical respiratory stimuli.

Acoustic Stimulation↗
PubMed1992

Respiratory system stability and abnormal carbon dioxide homeostasis.

We have tested the hypothesis that interactions among eight parameters of the respiratory and cardiovascular systems that determine the loop gain (LG) of the respiratory CO2 feedback control system might account for the degree of stability or instability of breathing patterns in healthy sleeping volunteers as well as in familial dysautonomia (FD) and congenital central hypoventilation syndrome (CCHS) patients. The predictability of cycle duration was tested as well. We measured the values of CO2 sensitivity, CO2 delivery capacity in the circulation, circulation delay, mean lung volume for CO2, and mixed venous PCO2 in 8 FD patients, 2 CCHS patients, and 19 healthy controls. The values of these parameters were used in a mathematical model to compute the LG of the respiratory control system during sleep for each epoch of respiration analyzed. The strength of the ventilatory oscillations (R) was quantified using power density spectra of the ventilation time series. All subjects were studied at inspiratory O2 concentrations (FIO2) of 0.21 and 0.15; CCHS patients and controls were also studied at 0.12 FIO2 to examine the effect of steady-state hypoxia on respiratory system stability. In 2 FD patients, LG was elevated at both levels of FIO2 and periodic breathing was observed; the values of R were elevated. Elevated mixed venous PCO2 and reduced CO2 delivery capacity were chiefly responsible for the abnormally high LG observed. In three healthy volunteers, high LG and unstable patterns were associated with high chemosensitivity. The CCHS patients, however, remained stable even at 0.12 FIO2 because LG remained equivalent to zero due to a lack of chemosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Upper airway muscle activity and the thoracic volume dependence of upper airway resistance.

Although a thoracic volume dependence of upper airway resistance and caliber is known to exist in seated subjects, the mechanisms mediating this phenomenon are unknown. To test the hypothesis that actively altered end-expiratory lung volume (EELV) affects upper airway resistance in the supine position and to explore the mechanisms of any EELV-induced resistance changes, we studied five normal males during wakefulness. Supraglottic upper airway resistance (Ruaw) was calculated at an inspiratory flow of 0.1 l/s. The genioglossal electromyogram was obtained with indwelling wire electrodes and processed as moving time average. End-tidal CO2 was monitored by infrared analyzer. Observations were made during four 20-breath voluntary maneuvers: two at high and two at low EELV in each subject. Each maneuver was preceded by a control period at functional residual capacity. At high lung volume the EELV was increased by 2.23 +/- 0.54 (SD) liters; Ruaw decreased to 67.8 +/- 35.1% of control, while tonic and phasic genioglossal activities declined to 79.0 +/- 23.1 and 72.4 +/- 29.8%, respectively. At low lung volume the EELV was decreased by 0.86 +/- 0.23 liters. Ruaw increased to 178.2 +/- 186.8%, while tonic and phasic genioglossal activities increased to 243.0 +/- 139.3 and 249.1 +/- 146.3%, respectively (P less than 0.0001 for all). The findings were not explained by CO2 perturbations or respiratory pattern. Multiple linear regression analysis indicated that the genioglossal responses blunted the EELV-induced changes in upper airway patency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Breath-by-breath respiratory timing and volume control during periodic breathing.

We examined the control of respiratory pattern during non-rapid-eye-movement sleep-related periodic breathing (PB) in adults, with and without hypoxia. We analyzed 186 cycles of PB from 18 epochs occurring in eight subjects; the mean (+/- SD) cycle duration was 30.8 +/- 8.4 s. Significant oscillations occurred in inspired tidal volume (VT), inspiratory duration (TI), mean inspired flow, inspired minute ventilation, and expiratory duration (TE) (P less than 0.005). For each epoch of PB, moving cross-correlation (MCC) functions were employed to describe the time-dependent intervariable relationships between 1) TI vs. TE, 2) VT vs. TE, and 3) VT vs. breath duration (TT) as synchronization, a strong and consistent intervariable correlation; relative coordination (RC), a weaker interaction characterized by an unstable MCC function oscillating at a subharmonic of the PB frequency; or as independence, with no statistical evidence of interaction. Fourteen epochs showed RC between TI and TE, 11 and 12 of which also showed RC between VT and TE, and VT and TT, respectively. In 4 epochs negative synchronization was exhibited by all three variable pairs. In no case were the oscillations between any pair of variables independent. The modes of coupling between variables were not correlated to O2 saturation, end-tidal CO2 levels, or inspired O2 level. We conclude that during sleep-related PB a nonrandom but weak coupling usually exists between TI and TE, VT and TE, and VT and TT.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1989

Upper airway and respiratory muscle responses to continuous negative airway pressure.

To determine upper airway and respiratory muscle responses to nasal continuous negative airway pressure (CNAP), we quantitated the changes in diaphragmatic and genioglossal electromyographic activity, inspiratory duration, tidal volume, minute ventilation, and end-expiratory lung volume (EEL) during CNAP in six normal subjects during wakefulness and five during sleep. During wakefulness, CNAP resulted in immediate increases in electromyographic diaphragmatic and genioglossal muscle activity, and inspiratory duration, preserved or increased tidal volume and minute ventilation, and decreased EEL. During non-rapid-eye-movement and rapid-eye-movement sleep, CNAP was associated with no immediate muscle or timing responses, incomplete or complete upper airway occlusion, and decreased EEL. Progressive diaphragmatic and genioglossal responses were observed during non-rapid-eye-movement sleep in association with arterial O2 desaturation, but airway patency was not reestablished until further increases occurred with arousal. These results indicate that normal subjects, while awake, can fully compensate for CNAP by increasing respiratory and upper airway muscle activities but are unable to do so during sleep in the absence of arousal. This sleep-induced failure of load compensation predisposes the airways to collapse under conditions which threaten airway patency during sleep. The abrupt electromyogram responses seen during wakefulness and arousal are indicative of the importance of state effects, whereas the gradual increases seen during sleep probably reflect responses to changing blood gas composition.

Abdominal Muscles↗
PubMed1989

Breath-by-breath interactions between inspiratory and expiratory duration in occlusive sleep apnea.

We examined interactions between inspiratory duration (TI), expiratory duration (TE), and inspiratory (esophageal) pressure (Pes) generation in seven subjects with confirmed occlusive sleep apnea. Breath-by-breath values of TI, TE, and Pes were identified by digital computer during 21 260-s epochs of repetitive occlusive apnea during non-rapid-eye-movement sleep. The control theory of interacting nonlinear oscillators was used to categorize the interaction between TI and TE for each epoch as either 1) synchronization, the strongest possible interaction between biological oscillators; 2) relative entrainment, a moderate interaction between oscillators; or 3) relative coordination, a weak interaction. The latter two interactions were characterized by systemic oscillations in the moving cross-correlation between TI and TE. The relationship between TI and Pes was analyzed in a similar fashion. Significant oscillations were present in all three parameters (P less than 0.0001 for each). We observed significant negative correlations between TI and TE and between TI and Pes (P less than 0.001 for each) when all breaths for all epochs were pooled. In no epoch was there a significant positive correlation between TI and TE or Pes. All three interactions were observed between TI and TE: five epochs of synchronization, nine of relative entrainment, and seven of relative coordination. In contrast, 19 of 21 epochs exhibited synchronization between TI and Pes, with 2 epochs of relative entrainment. The relative frequency of TI vs. Pes synchronization was significantly greater than TI vs. TE synchronization (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Relative stability of human respiration during progressive hypoxia.

We have systematically studied the relationship between the relative stability (R) of respiration and the loop gain (LG) of the CO2 control system in 15 healthy awake adult males during progressive hypoxia. R was measured by the ventilatory oscillations after brief (less than 10 s) CO2 challenges. Control theory suggests that such oscillations are completely governed by LG. A significant positive correlation was found between R and LG (r = 0.74, P less than 0.01, n = 85). A minimal mathematical model of respiratory control was used to predict R as a function of LG. Serial correlation analysis (r = 0.09, P greater than 0.1) of the residuals indicated statistical agreement between predictions and observations. The mean residual (0.011) was not significantly different from zero (P greater than 0.1). Also, as the model predicted, sustained periodic breathing (PB) occurred whenever the estimated LG was greater than unity. The mean LG breathing room air was 0.51 and for the 13 epochs of PB was 1.17 (range 0.71-1.65). It is concluded that PB is a quantitative extension of the relative stability continuum and corresponds to unstable operation of the CO2 control system. Furthermore, relative stability can be quantitatively predicted for each subject by a minimal mathematical model.

Adult↗
PubMed1988

A minimal mathematical model of human periodic breathing.

Numerous mathematical models of periodic breathing (PB) currently exist. These models suggest mechanisms that may underlie many known causes of PB. However, each model that has been shown to simulate PB under reasonable conditions contains greater than 15 physiological parameters. Because some parameters exhibit a wide range of values in a population, such simulations cannot test a model's ability to account for the breathing patterns of individuals. Furthermore it is impractical to perform a direct experimental validation study that would require the estimation of each of 15 or more parameters for each subject. A minimal model of PB is presented that is suitable for direct validation. Analytic expressions are given that define the conditions for PB in terms of the following: 1) CO2 sensitivity, 2) Cardiac output, 3) Mixed venous CO2, 4) Circulation time, and 5) Mean lung volume for CO2. This model is shown to be consistent with previous models and experimental data regarding the degree of hypoxia or congestive heart failure required to produce PB. A quantitative measure of relative stability is defined as a metric of comparison to the human studies described in the accompanying paper (J. Appl. Physiol. 65: 1389-1399, 1988).

Blood Circulation Time↗
PubMed1987

Evaluation of autonomic dysfunction in familial dysautonomia by power spectral analysis.

We examined the nature and extent of the autonomic control defect in patients with autonomic dysfunction using power spectral analysis of heart rate fluctuations. Heart rate variability and respiratory patterns were monitored and discrete blood pressure measurements were made during supine and standing positions in 10 ambulatory patients with familial dysautonomia and in controls. Postural hypotension without compensatory tachycardia was confirmed in the patients upon standing. The balance between sympathetic and parasympathetic activity was compared in both positions by quantifying the power of the low (0.04-0.095 Hz) and high (respiratory) frequency fluctuations in instantaneous heart rate. After changing from supine to standing position there was a small decrease in the low frequency power of heart rate fluctuations in the patients as opposed to a significant increase in controls. The mean power of fluctuations occurring at high frequency decreased only slightly in the patients compared to a marked decrease in the controls. We conclude that the fall in blood pressure, lack of appropriate heart rate modulation, and failure to increase low frequency heart rate power which occurred in the patients upon standing, are all due to lack of increased sympathetic output under the influence of gravity. The failure to decrease power in the respiratory frequency peak in the patients, suggests an abnormal retention of parasympathetic activity. This may be explained by parasympathetic compensation for the substantial sympathetic loss, or by a lack of appropriate inhibition of parasympathetic tone from baroreceptors or supraspinal structures.

Adult↗