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Biomedical subjects

J L Carroll

Publications and source records attributed to J L Carroll.

At least 37 records · Page 2Linked to original sources

Mechanisms of carotid chemoreceptor resetting after birth. In vitro studies.

The results of these studies are consistent with the hypothesis that carotid chemoreceptor type-I cell resetting occurs, at least in part, at the level of the type-I cell. Furthermore, we have developed an in vitro model of newborn type-I cell resetting, in which freshly isolated glomus cells from newborns exhibit small, immature [Ca2+]i response to anoxia, but-after 72 hours in culture-[Ca2+]i responses convert to adult magnitude and profile. Finally, work so far suggests that glomus cell resetting in this model is modulated by oxygen tension. The mechanisms of glomus cell resetting remain unknown. Resetting of O2 sensitivity could result from withdrawal of tonic inhibitory influences present in vivo, changes in the oxygen sensor itself, changes in ion channel expression, modulation, and function, or other mechanisms occurring around the time of birth. Additional work is needed to determine the mechanisms of glomus cell resetting at the cellular level, and the role of O2 tension and other potential modulators of resetting.

Animals↗

Effect of nicotine exposure on postnatal ventilatory responses to hypoxia and hypercapnia.

The risk of SIDS is increased up to fourfold by maternal smoking, by an unknown mechanism. We tested the hypothesis that prenatal nicotine exposure can cause abnormal postnatal development of breathing control. Osmotic minipumps were implanted into pregnant rats to deliver either nicotine bitartrate (6 mg kg-1 day-1) (NIC) or saline (CON) throughout gestation and for 1 week postnatal. NIC and CON rat pups from 4 age groups (means 3, 8, 18 and 34 days) were studied. Ventilation was recorded at 30 degrees C in air and after 10 min at FIO2 = 0.1 and 0.15, and at FICO2 = 0.05. Ventilatory responses to FIO2 = 0.1 and FICO2 = 0.05 showed significant changes with age but were unaffected by NIC at all ages. The weak respiratory responses to FIO2 = 0.15 were unaffected by NIC or age. Oxygen consumption in normoxia and hypoxia, and hypoxic depression of oxygen consumption, declined with age but were not affected by NIC. We conclude that NIC exposure alone has no detectable effect on the postnatal development of respiratory responses to moderate levels of hypoxia or hypercapnia for short periods. However, effects of NIC on the responses to more severe or prolonged stimuli cannot be ruled out.

Analysis of Variance↗

Ventral medullary neuronal responses to peripheral chemoreceptor stimulation.

Recent findings suggest that carotid chemoreceptor input into the ventral medullary surface intermediate area during hypoxia is inhibitory (Gozal et al., (1994) Neurosci. Lett. 178, 73-76. However, systemic hypoxia is a complex stimulus, and effects of carotid chemoreceptor stimulation per se on intermediate ventral medullary surface neuronal activity are difficult to isolate. Therefore, we studied neural activation of the intermediate ventral medullary surface during peripheral chemoreceptor stimulation by intravenous sodium cyanide using optical procedures in seven pentobarbital-anesthetized cats. Control recordings were also acquired in the suprasylvian cortex of three cats. Images of reflected 660 nm light were collected at l/s with a charge-coupled device camera, triggered by the cardiac R wave, after 0.0, 0.5, 2, 5, 10, 20 and 40 micrograms/kg i.v. sodium cyanide administration before and following carotid sinus denervation. Sodium cyanide doses > 5 micrograms/kg significantly increased ventilation, an effect which was eliminated following carotid sinus denervation. A pronounced, dose-dependent activity decrease within the intermediate ventral medullary surface occurred within seconds of sodium cyanide administration, with subsequent return to baseline. Carotid sinus denervation eliminated rapid-onset neural responses to all sodium cyanide doses. However, at the 40 micrograms/kg dose, a smaller, slower onset (25 s), activity decrease occurred both pre- and postdenervation. In the neocortex, the sodium cyanide-induced fast responses were absent. Intravenous cyanide, acting via a carotid sinus nerve pathway, results in a dose-dependent decrease in neural activity within the intermediate ventral medullary surface of cats. High-dose sodium cyanide also appears to decrease intermediate ventral medullary surface neural activity directly.

Animals↗

Ventral medullary surface responses to hypoxic and hyperoxic transient ventilatory challenges in the cat.

Carotid body afferent contributions to activity of the intermediate area of the ventral medullary surface (IVMS) following transient hypoxia and hyperoxia were examined in 6 spontaneously breathing, pentobarbital-anesthetized cats. Two tidal breaths of 100% N2, 100% O2, or room air, were randomly administered before and after carotid sinus denervation (CSD). Images of scattered light from the IVMS showed that activity increased with hypoxia (10.1 +/- 2.4%), and decreased with hyperoxia (4.8 +/- 1.8%). CSD significantly increased the magnitude and delayed the onset of the hypoxic response, but reversed the initial component of the hyperoxic response. We conclude that carotid body afferents modulate the magnitude and timing of IVMS responses to transient respiratory challenges.

Animals↗

Developmental changes in intracellular Ca2+ response of carotid chemoreceptor cells to hypoxia.

The carotid chemoreceptor response to hypoxia is weak just after birth and increases during postnatal development. The mechanisms underlying chemoreceptor maturation are unknown. We tested the hypothesis that carotid chemoreceptor maturation occurs at the glomus cell level by measuring intracellular calcium ([Ca2+]i) mobilization in response to hypoxia, anoxia, and NaCN in freshly dissociated cells from newborn vs. adult rabbit carotid bodies. Cells were loaded with fura 2 and superfused at 37 degrees C with balanced salt solution equilibrated with 5% CO2. [Ca2+]i mobilization in response to 3-min challenges of hypoxia (PO2 approximately 15 mmHg), anoxia (PO2 approximately 0 mmHg), and NaCN (1 mM) was measured using a digital imaging microscope. The fluorescence intensity ratio was used to calculate [Ca2+]i. Peak [Ca2+]i responses to all three challenges were three- to fivefold greater in glomus cells from adult compared with newborn carotid chemoreceptors. In addition, the average normoxic [Ca2+]i baseline was approximately threefold higher in the adult glomus cells. These results suggest that carotid chemoreceptor glomus cell sensitivity to natural stimuli, as reflected by the [Ca2+]i response, depends on the level of postnatal maturity.

Aging↗

Pressor-induced responses of the cat ventral medullary surface.

We examined ventral medullary surface activity using light reflectance procedures after blood pressure alterations induced by phenylephrine or sodium nitroprusside in 23 pentobarbital sodium-anesthetized cats. Images of reflected 660-nm light were collected and digitized at 1- to 3-s intervals after baseline and intravenous saline, 5-40 micrograms/kg phenylephrine, or sodium nitroprusside infusion. Carotid sinus nerve denervation (CSD) and bilateral vagotomy were performed in five and three animals, respectively, and challenges were repeated. Phenylephrine elicited a dose-dependent transient blood pressure elevation and reflectance increase (interpreted as activity decline) over the entire ventral medullary surface examined. The increase consisted of an initial rapid transient component, peaking at 45 s, and a 3- to 5-min recovery. CSD enhanced, and vagotomy substantially reduced, the initial transient response to phenylephrine. Sodium nitroprusside-induced lowering of blood pressure was associated with decreased reflectance in rostral sites and increased reflectance in caudal regions. CSD abolished a late component and diminished amplitude of an initial rapidly rising component of changes induced by nitroprusside, a decline further accentuated by addition of vagotomy.

Animals↗

Supplemental oxygen during sleep in children with sleep-disordered breathing.

Supplemental O2 is sometimes used to treat children with the obstructive sleep apnea syndrome (OSAS). However, its effects have not been studied. We therefore evaluated the use of supplemental O2 during sleep in children with OSAS. Oxygen and room air were delivered via nasal cannula at 1 L/min for 4 h each in a randomized, double-blind fashion. Twenty-three children were studied (mean age, 5 +/- 3 [SD] yr). Patients had a higher mean SaO2 and higher SaO2 nadir when breathing O2. There was no difference in the number (10.9 +/- 20.6/h on O2 versus 13.5 +/- 19.3 on room air) or duration of obstructive apneas. Although there was no overall change in end-tidal PCO2 when patients breathed O2, two children showed a significant increase. We conclude that breathing supplemental O2 during sleep in children with OSAS results in improved oxygenation and in most cases does not exacerbate sleep-disordered breathing. However, end-tidal PCO2 should be monitored in children with OSAS receiving O2 therapy. We speculate that supplemental O2 does not depress the ventilatory drive during sleep in most children with OSAS.

Child↗

Inability of clinical history to distinguish primary snoring from obstructive sleep apnea syndrome in children.

STUDY OBJECTIVE: To determine whether primary snoring (PS) could be distinguished from childhood obstructive sleep apnea syndrome (OSAS) by clinical history. DESIGN: Retrospective study of clinical history of 83 children with snoring and/or sleep disordered breathing who were referred for polysomnography. SETTING: Tertiary referral center; pediatric pulmonary sleep apnea clinic. MEASUREMENTS: We evaluated the ability of a clinical obstructive sleep apnea (OSA) score and other questions about sleep, breathing, and daytime symptoms to distinguish PS from OSAS in children. Parents were asked about the child's snoring, difficulty breathing, observed apnea, cyanosis, struggling to breathe, shaking the child to "make him or her breathe," watching the child sleep, afraid of apnea, the frequency and loudness of snoring, and daytime symptoms such as excessive daytime sleepiness (EDS). RESULTS: Based on polysomnography results, 48 patients were classified as PS and 35 as OSAS. Peak endtidal CO2 (49 +/- 3.2 vs 55 +/- 8.2 [SD] mm Hg); lowest arterial oxygen saturation measured by pulse oximetry (95 +/- 1.9 vs 82 +/- 14%); and apnea/hypopnea index (0.27 +/- .3 vs 8.4 +/- 6 events/h) indicated that the diagnostic criteria for PS versus OSA were reasonable. There were no differences between PS and OSA patients with respect to age, sex, race, failure to thrive, obesity, history of EDS, snoring history, history of cyanosis during sleep, or daytime symptoms except for mouth breathing. There were no significant differences in sleep variables between PS patients and those with any severity of OSAS. The OSA score misclassified about one of four patients. Comparing PS and OSA patients, significant findings were daytime mouth breathing (61 vs 85%; p = 0.024); observed apnea (46 vs 74%; p = 0.013); shaking the child (31 vs. 60%; p = 0.01); struggling to breathe (58 vs 89%; p = 0.003); and afraid of apnea (71 vs 91%; p = 0.028). However, none of these were sufficiently discriminatory to predict OSAS. CONCLUSION: We conclude that PS in children cannot be reliably distinguished from OSAS by clinical history alone.

Case-Control Studies↗

Alcohol use and risky sex among college students.

Undergraduates, 55 men and 151 women, completed a 13-item survey about drinking behavior and sexual activity. In general, men and women were similar in their behaviors. Despite recent efforts to promote AIDS awareness, it appears that both genders may be engaging in risky behavior. The results are discussed in terms of educational efforts aimed at AIDS prevention.

Acquired Immunodeficiency Syndrome↗

Afferent contributions to intermediate area of the cat ventral medullary surface during mild hypoxia.

The intermediate area of the cat ventral medullary surface activates to mild hypoxia. Carotid body and vagal afferent contributions to this response were examined by recording activity levels, measured as changes in scattered 660 nm light, from the medullary surface in 7 anesthetized, spontaneously breathing cats following 12% O2 in N2 ventilatory challenge. A miniaturized video camera collected images synchronous with the peak of cardiac R wave at 1/s, from a 3.2 mm diameter area, before, and following bilateral carotid sinus denervation (CSD) and vagotomy. In intact animals, hypoxia increased activity; however, greater increases in activity levels followed CSD, while vagotomy elicited a marked reduction of the response. Thus, carotid body afferents exert inhibitory or disfacilitatory influences on intermediate area neurons, while the vagus appears to play an excitatory role.

Afferent Pathways↗

Determinants of growth in children with the obstructive sleep apnea syndrome.

Failure to thrive is a common complication of childhood obstructive sleep apnea syndrome (OSAS). To further evaluate its cause, we obtained 3-day dietary records, anthropometric measurements, polysomnography, and measurements of energy expenditure during sleep (SEE) in children with OSAS before and after tonsillectomy and adenoidectomy. Fourteen children were studied (mean age, 4 +/- 1 (SD) years). During initial polysomnography, patients had 6 +/- 3 episodes of obstructive apnea/hr, an arterial oxygen saturation nadir of 85% +/- 8%, and peak end-tidal carbon dioxide tension of 52 +/- 6 mm Hg. After surgery, OSAS resolved in all patients. The standard deviation score (z score) for weight increased from -0.30 +/- 1.47 to 0.04 +/- 1.34 (p < 0.005), despite unaltered caloric intake (91 +/- 30 vs 90 +/- 27 kcal/kg per day; not significant). The initial SEE (averaged over all sleep states) was 51 +/- 6 kcal/kg per day; postoperatively, it decreased to 46 +/- 7 kcal/kg per day (p < 0.005). Although SEE decreased during all sleep stages, the greatest decrease occurred during rapid eye movement sleep. The patients with the highest SEE on initial study had the lowest z scores (r = -0.62; p < 0.05). We conclude that SEE decreases and weight improves after resolution of OSAS. We speculate that the poor growth seen in some children with OSAS is secondary to increased caloric expenditure caused by increased work of breathing during sleep.

Child↗

Polysomnographic characteristics of patients with Rett syndrome.

During wakefulness, patients with Rett syndrome have disordered breathing. To understand further this ventilatory control disorder, we performed polysomnography in 30 patients with Rett syndrome and 30 control subjects (female subjects with primary snoring). The median age was 7 years (range, 1 to 32 years) for Rett syndrome and 6 years (range, 1 to 17 years) for control subjects. During periods of wakefulness, 67% of patients with Rett syndrome had the characteristic pattern of disordered breathing (i.e., episodes of hyperventilation followed by central apnea and desaturation). No such events occurred during sleep. Sleep efficiency and sleep architecture were similar for both groups. During sleep, there was no difference in duration of periodic breathing, number of episodes of central apnea with desaturation, or number of episodes of obstructive apnea or end-tidal carbon dioxide tension between the two groups. Although arterial oxygen saturation during rapid eye movement (REM) sleep was slightly lower in patients with Rett syndrome (nadir, 94% +/- 2% vs 96% +/- 2%), it remained within the normal range. Parental history reflected the awake respiratory findings in most cases. We conclude that patients with Rett syndrome have normal breathing during non-rapid eye movement (NREM) sleep. We speculate that patients with Rett syndrome have normal brain-stem control of ventilation, and that the disordered breathing seen during wakefulness is due to an abnormality of the cortical influence on ventilation.

Adolescent↗

Upper airway collapsibility in children with obstructive sleep apnea syndrome.

In adults, the critical nasal pressure (Pcrit) at which the upper airway collapses is higher in patients with the obstructive sleep apnea syndrome (OSAS) than in those with primary snoring. Pediatric OSAS differs clinically from adult OSAS. We therefore compared Pcrit between prepubertal children with OSAS and primary snoring. Pcrit was determined by correlating the maximal inspiratory airflow with the level of positive or negative nasal pressure applied via a nasal mask. As in adults, we found that the maximal inspiratory airflow varied in proportion to the upstream (nasal) rather than the downstream (esophageal) pressure changes. Pcrit was 1 +/- 3 cmH2O in OSAS compared with -20 +/- 9 cmH2O in primary snorers (P < 0.002). In three OSAS patients reevaluated after tonsillectomy and adenoidectomy, Pcrit declined to -7.2 +/- 4.0 cmH2O. We conclude that the pediatric airway behaved as predicted by the Starling resistor model and that Pcrit, a measure of airway collapsibility, correlated with the degree of upper airway obstruction and was reduced postoperatively, consistent with increased upper airway stability.

Adenoids↗

Effects of domperidone on neonatal and adult carotid chemoreceptors in the cat.

It has been postulated that the weak carotid chemoreceptor responses of neonatal mammals may be due to inhibition produced by high levels of endogenous dopamine release or exaggerated sensitivity to dopaminergic inhibition. This was studied by measuring the effect of domperidone, a selective dopamine D2-receptor antagonist, on the carotid chemoreceptor response to O2 and CO2 in anesthetized neonatal and adult cats. The animals were exposed to four levels of isocapnic O2 (arterial PO2 of approximately 35-45, 55-65, 80-90, > 300 Torr) and four levels of isoxic CO2 (end-tidal PCO2 of approximately 21, 40, 58, and 78 Torr) before and after D2-receptor blockade. Whole nerve activity was recorded from the carotid sinus nerve (CSN). Both neonatal and adult cats increase CSN activity during hypoxia and hypercapnia (P < 0.001). Domperidone caused an increase in CSN activity at all O2 levels in adults (P < 0.01) but only during hypoxia in neonates (P < 0.001). Domperidone caused an increase in CSN activity during normo- and hypercapnia in adults but only during hypercapnia in neonates (P < 0.001). Domperidone approximately doubled an index of hypoxic sensitivity in the normoxia-hypoxia range (100 to 40 Torr) in the neonatal group but had little effect on sensitivity to hypoxia in adults. We conclude that the inhibitory role of endogenous dopamine in the carotid chemoreceptors changes with postnatal development.

Animals↗

Concurrent validity of the Culture-free Self-esteem Inventory and physical health in college students.

55 college students received the Culture-free Self-esteem Inventory and a 13-item measure of physical health; significant Pearson correlations (generally in the .40s) were found on all but one subscale of the self-concept measure and the health measure. The results are in line with research using other measures of self-esteem and physical health and suggest that the self-esteem inventory may be useful as a research measure.

Adolescent↗