Biomedical subjects

Safraaz Mahamed

Publications and source records attributed to Safraaz Mahamed.

6 recordsLinked to original sources

PubMed2006

Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea?

Although neuroplasticity is an important property of the respiratory motor control system, its existence has been appreciated only in recent years and, as a result, its functional significance is not completely understood. The most frequently studied models of respiratory plasticity is respiratory long-term facilitation (LTF) following acute intermittent hypoxia and enhanced LTF following chronic intermittent hypoxia. Since intermittent hypoxia is a prominent feature of sleep-disordered breathing, LTF and/or enhanced LTF may compensate for factors that predispose to sleep-disordered breathing, particularly during obstructive sleep apnoea (OSA). Long-term facilitation has been studied most frequently in rats, and exhibits interesting properties consistent with a role in stabilizing breathing during sleep. Specifically, LTF: (1) is prominent in upper airway respiratory motor activity, suggesting that it stabilizes upper airways and maintains airway patency; (2) is most prominent during sleep in unanaesthetized rats; and (3) exhibits sexual dimorphism (greatest in young male and middle-aged female rats; smallest in middle-aged male and young female rats). Although these features are consistent with the hypothesis that upper airway LTF minimizes the prevalence of OSA in humans, there is little direct evidence for such an effect. Here we review advances in our understanding of LTF and its underlying mechanisms and present evidence concerning a potential role for LTF in maintaining upper airway patency, stabilizing breathing and preventing OSA in humans. Regardless of the relationship between LTF and OSA, a detailed understanding of cellular and synaptic mechanisms that underlie LTF may guide the development of new drugs to regulate upper airway tone, thereby offsetting the tendency for upper airway collapse characteristic of heavy snoring and OSA.

Animals↗

PubMed2005

Overnight changes of chemoreflex control in obstructive sleep apnoea patients.

We hypothesized that the numerous episodes of hypoxia, hypercapnia and arousal experienced by obstructive sleep apnoea (OSA) patients induce overnight changes in respiratory chemoreflexes. A modification of the Read rebreathing technique assessed chemoreflex characteristics in the evening and the morning of patients undergoing diagnostic assessment for OSA in a clinical sleep laboratory. Two groups were studied: those with apnoea-hypopnoea indices (AHI) greater than 30 composed the OSA group (n = 12), and those with AHI indices less than 10 composed the non-OSA group (n = 12). There was a significant (approximately 30%) overnight increase in chemoreflex sensitivities, without changes in thresholds, in the OSA group. In the non-OSA group there was a significant overnight reduction in chemoreflex thresholds (approximately 5%), without changes in sensitivities. We suggest that these changes affect the stability of the chemoreflex control system in opposite ways as the night proceeds: destabilizing breathing for patients in the OSA group, and stabilising breathing for patients in the non-OSA group.

Adult↗

PubMed2004

Cardio-respiratory measures following isocapnic voluntary hyperventilation.

In some individuals, breathing is greater than at rest following voluntary hyperventilation. Most previous investigations have employed short hyperventilation periods; here we examine the time course of cardio-respiratory measures before, during, and after a 5-min voluntary hyperventilation, maintaining isocapnia throughout. We examined the possible co-involvement of the cardiovascular system; hypothesising that post-hyperventilation hyperpnoea results from an increase in autonomic arousal. In four subjects (two males, two females) of 18 (nine males, nine females) we observed a post-hyperventilation hyperpnoea, characterised by a slow decline of ventilation toward resting levels with a time constant of 109.0 +/- 16.1s. By contrast, heart rate, and systolic and diastolic blood pressure were unchanged from rest during and after voluntary hyperventilation for all subjects. We concluded that males and females were equally likely to exhibit post-hyperventilation hyperpnoea, and suggest that they may be characterised by an increased resting heart rate and the choice of breathing frequency to increase ventilation during the voluntary hyperventilation. We further concluded that post-hyperventilation hyperpnoea is rare, but when present is a strong and lasting phenomenon, and that it is not the result of an increased autonomic arousal.

Adult↗

PubMed2003

Adaptation in the respiratory control system.

Exposure to hypoxia, whether for short or prolonged periods or for repeated episodes, produces alterations in the ventilatory responses. This review presents evidence that these adaptations are likely to be mediated by adaptations in the respiratory chemoreflexes, particularly the peripheral chemoreflex, and proposes models of respiratory control explaining the observed changes in ventilation. After a brief introduction to the respiratory control system, a graphical model is developed that illustrates the operation of the system in the steady state, which will be used later. Next, the adaptations in ventilatory responses to hypoxia that have been observed are described, and methods of measuring the alterations in the chemoreflexes that might account for them are discussed. Finally, experimental data supporting the view that changes in the activity of the peripheral chemoreflex can account for the ventilatory adaptations to hypoxia are presented and incorporated into models of chemoreflex behaviour during exposures to hypoxia of various durations.

Adaptation, Physiological↗

PubMed2002

Changes in respiratory control after three hours of isocapnic hypoxia in humans.

Despite the obvious role of hypoxia in eliciting respiratory acclimatisation in humans, the function of the peripheral chemoreflex is uncertain. We investigated this uncertainty using 3 h of isocapnic hypoxia as a stimulus (end-tidal PCO2, 0.5-1.0 mmHg above eucapnia; end-tidal PO2, 50 mmHg), hypothesising that this stimulus would induce an enhancement of the peripheral chemoreflex ventilatory response to hypoxia. Current evidence conflicts as to whether this enhancement is mediated by an increase in the sensitivity or a decrease in the threshold of the peripheral chemoreflex ventilatory response to carbon dioxide. Employing a modified rebreathing technique to assess chemoreflex function, we found evidence of the latter in nine healthy volunteers (six male, three female). Testing consisted of pairs of isoxic rebreathing tests at high and low levels of oxygen, performed before, immediately after and 1 h after a 3 h isocapnic hypoxic exposure. No parameters changed significantly in the high-oxygen rebreathing tests. In the low-oxygen rebreathing tests there were no changes in non-chemoreflex ventilatory drives, or in the sensitivity to carbon dioxide, but the carbon dioxide response threshold decreased (approximately 1.5 mmHg) immediately after exposure, and the decrease persisted for 1 h (one-way repeated-measures ANOVA; P < 0.05). We repeated the protocol in five of the original nine volunteers, but this time exposing them to isocapnic normoxia. No trends or significant changes were observed in any of the rebreathing test parameters. These findings demonstrate that in the earliest stages of acclimatisation, there is a decrease in the threshold of the peripheral chemoreflex response to carbon dioxide, which persists for at least 1 h after the return to normoxia. We suggest that ventilatory acclimatisation to hypoxia results from this decreased threshold, reflecting an increase in the activity of the peripheral chemoreflex.

Acclimatization↗

PubMed2002

Central and peripheral chemoreflexes in panic disorder.

Klein (Arch Gen Psychiatry, 50, 1993, 306-317) has suggested that panic disorder patients have a false suffocation alarm that may be associated with a lowered threshold for carbon dioxide detection. We compared the thresholds and sensitivities of the central and peripheral chemoreflexes between panic disorder patients and age- and sex-matched healthy volunteers to test this aspect of the hypothesis. We used a modified version of Read's rebreathing technique in 11 panic disorder patients and 10 healthy volunteers to examine the peripheral and central chemoreflex characteristics in these two populations. Subjects were examined during three rebreathing tests: training, hyperoxic (central chemoreflex alone) and hypoxic (combined central and peripheral chemoreflex). Panic symptoms were retrospectively assessed between groups using a DSM-IV derived Panic Symptom Scale. Comparisons of panic disorder patients with agoraphobia and healthy volunteers showed no significant differences in sensitivities or thresholds. Klein's hypothesis is not supported by these data. If a false suffocation alarm exists, its triggering may not be implemented within the respiratory chemoreflexes.

Adult↗