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.     

Sputum induction as a research tool for the study of human respiratory mucus

The study objectives were to compare in vitro transportability and physical properties of respiratory mucus, obtained invasively by direct collection (DC) right after endotracheal intubation and non-invasively by sputum induction with 3% hypertonic saline solution inhalation (SI) 24 h before the anesthesia. Twenty-two patients with no pulmonary disease scheduled for elective abdominal surgical procedures were studied. The parameters analyzed and the main results are as follows. (1) Transportability by cilia (MCT), SI was higher than DC (0.94+/-0.25 and 0.62+/-0.25; P<0.001). There was a significant correlation between the two methods and DC could be estimated by: DC=0.21+(0.44 SI) (r=0.44; P<0.001). (2) Transportability by cough (CC), SI was higher than DC (68.23+/-32.1 and 33.58+/-19.04 mm; P=0.002). (3) Contact angle (CA), SI was lower than DC (10+/-3 degrees and 22+/-14 degrees ; P=0.025). (4) Rheological properties (no significant difference obtained between SI and DC). These results indicated that SI changes mucus physical properties and transportability in non-expectorators.     

Effects of tryptophan depletion on central and peripheral chemoreflexes in man

Klein (Arch. Gen. Psychiatry 50, 306-317, 1993) suggests that panic attacks are the result of a defective 'suffocation alarm' threshold that presents with carbon dioxide (CO(2)) hypersensitivity, exaggerated ventilatory response and panic in panic disorder (PD) patients. Serotonergic deficiencies enhance this ventilatory response in PD patients, as per 'suffocation alarm' theory predictions, suggesting that serotonin (5-HT) normalizes the ventilatory response. Other research supports a serotonin system-mediated stimulation of ventilation. Knowledge of 5-HT's role on ventilatory output and its neurophysiological sources impacts on the 'suffocation alarm' theory validity and predictive value. We used tryptophan depletion (TRP-) in concert with a modified Read rebreathing test to determine the effect of deficient serotonergic modulation on the central and peripheral chemoreflex threshold and sensitivity of response to CO(2) in 11 healthy men. TRP- did not affect central or peripheral chemoreflex threshold or sensitivity of response to CO(2). However, basal ventilation was significantly elevated during TRP-. In contrast to 'suffocation alarm' theory predictions, decreased 5-HT neurotransmission does not significantly affect the respiratory chemoreflex response to CO(2), impacting on non-chemoreflex drives to breathe. Panic associated respiratory abnormalities may be related to defective 5-HT modulation of non-chemoreflex drives to breathe, unrelated to any respiratory chemoreflex abnormality.     

A tidal ventilation model for oxygenation in respiratory failure

We develop tidal-ventilation pulmonary gas-exchange equations that allow pulmonary shunt to have different values during expiration and inspiration, in accordance with lung collapse and recruitment during lung dysfunction (Am. J. Respir. Crit. Care Med. 158 (1998) 1636). Their solutions are tested against published animal data from intravascular oxygen tension and saturation sensors. These equations provide one explanation for (i) observed physiological phenomena, such as within-breath fluctuations in arterial oxygen saturation and blood-gas tension; and (ii) conventional (time averaged) blood-gas sample oxygen tensions. We suggest that tidal-ventilation models are needed to describe within-breath fluctuations in arterial oxygen saturation and blood-gas tension in acute respiratory distress syndrome (ARDS) subjects. Both the amplitude of these oxygen saturation and tension fluctuations, and the mean oxygen blood-gas values, are affected by physiological variables such as inspired oxygen concentration, lung volume, and the inspiratory:expiratory (I:E) ratio, as well as by changes in pulmonary shunt during the respiratory cycle.     

A simple breathing circuit to maintain isocapnia during measurements of the hypoxic ventilatory response

We report the development and testing of a simple breathing circuit that maintains isocapnia in human subjects during hypoxic hyperpnea. In addition, the circuit permits rapid switching between two gas mixtures with different partial pressures of oxygen. Eleven volunteers breathed repeated cycles of exposure to air (2 min of 21% O(2), balance N(2)) and hypoxia (2 min of 8.3+/-0.1% O(2), balance N(2)). Hypoxia induced significant increases in minute ventilation, breathing frequency and tidal volume (P < 0.05) that were consistent over repeated cycles of hypoxia (P > 0.1, one-way ANOVA). The system successfully maintained isocapnia in all subjects, with an average change in end-tidal CO(2) of only -0.2 mmHg during hyperventilation in hypoxia (range 0.4 to -0.8 mmHg). This system may be suitable for repeated tests of the hypoxic ventilatory response (HVR) and may prove useful for exploring intra- and inter-individual variability of HVR in humans.     

Extra- and intracellular free iron and the carotid body responses

The hypothesis that chelation of free iron, by decreasing reactive oxygen species (ROS), might mimic hypoxia and stimulate the carotid body was tested. We used the iron chelators, desferrioxamine (DFO, 200-400 microM) initially, and later ciclopirox olamine (CPX, 2.5-5.0 microM), on rat carotid body in vitro and measured chemosensory activity and [Ca2+]i in isolated cultured glomus cell clusters during normoxia and hypoxia. Although acute treatment of DFO might not penetrate the cell, and extracellular DFO would not influence these activities whereas CPX significantly increased chemosensory activities as well as increased [Ca2+]i in normoxia. We concluded that chelation of extracellular free iron did not alter ROS formation and oxygen sensing. Chelation of intracellular free iron and, therefore, a decrease in intracellular ROS appears to influence oxygen sensing in the carotid body.     

Airway smooth muscle: immunomodulatory cells that modulate airway remodeling?

Although the pathogenesis of asthma remains unclear, substantial progress has been made over the past decades in the characterization of airway inflammation as a pathogenetic mechanism in asthma. New evidence suggests that airway smooth muscle (ASM), the most important cell modulating bronchomotor tone, plays an important immunomodulatory role in the orchestration and perpetuation of airway inflammation. Evidence now suggests that the signaling pathways that modulate leukocyte function may be disparate from those found in resident effector cells such as ASM, fibroblasts and epithelial cells. Further investigation and understanding of the critical signaling pathways that modulate ASM cell release, secretion of chemokines/cytokines and expression of cell adhesion molecules (CAMs) may offer new therapeutic approaches in the treatment of asthma.     

The effects of cycle racing on pulmonary diffusion capacity and left ventricular systolic function

The purpose of this study was to examine the effects of a 20 km cycle race (TT) on left ventricular (LV) systolic and pulmonary function in 12 endurance cyclists. Spirometry, single-breath diffusion capacity (DLCO) with partitioning of membrane (DM) and capillary blood volume (Vc) components and 2-D echocardiograms were performed before and after the TT. During the TT mean oxygen consumption was 3.79 +/- 0.5 L x min(-1) (83 +/- 5.5% of VO2max) and mean blood lactate was 8.4 +/- 2.4 mM. Following the TT, spirometry values were unchanged, however, DLCO and DM were significantly (P<0.05) reduced. LV systolic function was increased (P<0.05) immediately after exercise, while end-diastolic area was decreased (P<0.05) at all points during recovery. The reduction in DM was correlated with LV systolic function following the TT. This relationship suggests a cardiovascular contribution to pulmonary diffusion impairment following exercise.     

Respiratory chemoreflexes and effects of cortical activation state in urethane anesthetized rats

Urethane anesthetized (< 1 .3 g/kg), Sprague-Dawley (SD) rats spontaneously cycled between a cortically desynchronized state (State I) and a cortically synchronized state (State III), which were very similar to awake and slow wave sleep (SWS) states in unanesthetized animals, based on EEG criteria. These low levels of urethane anaesthesia did not cause significant respiratory depression or reductions in sensitivity to hypoxia (10% O2 in nitrogen) or hypercapnia (5% CO2 in air) in rats in either State I or State III. Thus, breathing frequency (fR), tidal volume (VT) and total ventilation (VTOT) all increased on cortical activation in urethane-anaesthetized rats whether breathing air, the hypoxic or the hypercapnic gas mixture, in a manner that was very similar to that observed in unanaesthetized animals. The relative sensitivity to hypoxia was greater in State III than State I, the relative sensitivity to CO2, overall, was equal in both states, State III occurred less often during hypoxia and hypercapnia, and hypoxic, urethane-anaesthetized rats sighed frequently, particularly in State I. This is also similar to the situation seen in unanesthetized rats. Given the similarities seen between urethane anesthetized rats in the present study and literature values for unanesthetized rats, the data suggest that urethane-anaesthetized rats provide a good model system for studying respiratory patterns and chemoreflexes as a function of cortical activation state.