Functional optical coherence tomography at altitude: retinal microvascular perfusion and retinal thickness at 3,800 meters.

Cerebral hypoxia is a serious consequence of several cardiorespiratory illnesses. Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into cerebral hypoxia in critical illness. In addition, although sex-specific differences in cardiovascular diseases are strongly supported, few have focused on differences in ocular blood flow.

Duration at high altitude influences the onset of arrhythmogenesis during apnea.

Purpose: Autonomic control of the heart is balanced by sympathetic and parasympathetic inputs. Excitation of both sympathetic and parasympathetic systems occurs concurrently during certain perturbations such as hypoxia, which stimulate carotid chemoreflex to drive ventilation. It is well established that the chemoreflex becomes sensitized throughout hypoxic exposure; however, whether progressive sensitization alters cardiac autonomic activity remains unknown.

Identifying a Heart Rate Recovery Criterion After a 6-Minute Walk Test in COPD.

Background: Slow heart rate recovery (HRR) after exercise is associated with autonomic dysfunction and increased mortality. What HRR criterion at 1-minute after a 6-minute walk test (6MWT) best defines pulmonary impairment?.

Study Design And Methods: A total of 5008 phase 2 COPDGene (NCT00608764) participants with smoking history were included.

Asthmatic allergen inhalation sensitises carotid bodies to lysophosphatidic acid.

The carotid bodies are multimodal sensors that regulate various autonomic reflexes. Recent evidence demonstrates their role in immune reflex regulation. Our previous studies using the allergen (ovalbumin) sensitised and exposed Brown Norway rat model of asthma suggest that carotid bodies mediate asthmatic bronchoconstriction through a lysophosphatidic acid (LPA) receptor (LPAr)-protein kinase C epsilon (PKCε)-transient receptor potential vanilloid one channel (TRPV1) pathway.

Severity of central sleep apnea does not affect sleeping oxygen saturation during ascent to high altitude.

Central sleep apnea (CSA) is characterized by periodic breathing (PB) during sleep, defined as intermittent periods of apnea/hypopnea and hyperventilation, with associated acute fluctuations in oxyhemoglobin saturation (SO). CSA has an incidence of ∼50% in heart failure patients but is universal at high altitude (HA; ≥2,500 m), increasing in severity with further ascent and/or time at altitude. However, whether PB is adaptive, maladaptive, or neutral with respect to sleeping SO at altitude is unclear.

The effects of acute incremental hypocapnia on the magnitude of neurovascular coupling in healthy participants.

The high metabolic demand of cerebral tissue requires that local perfusion is tightly coupled with local metabolic rate (neurovascular coupling; NVC). During chronic altitude exposure, where individuals are exposed to the antagonistic cerebrovascular effects of hypoxia and hypocapnia, pH is maintained through renal compensation and NVC remains stable. However, the potential independent effect of acute hypocapnia and respiratory alkalosis on NVC remains to be determined.

Time course and magnitude of ventilatory and renal acid-base acclimatization following rapid ascent to and residence at 3,800 m over nine days.

Rapid ascent to high altitude imposes an acute hypoxic and acid-base challenge, with ventilatory and renal acclimatization countering these perturbations. Specifically, ventilatory acclimatization improves oxygenation, but with concomitant hypocapnia and respiratory alkalosis. A compensatory, renally mediated relative metabolic acidosis follows via bicarbonate elimination, normalizing arterial pH(a).

PKCε stimulation of TRPV1 orchestrates carotid body responses to asthmakines.

Key Points: We have previously shown that carotid body stimulation by lysophosphatidic acid elicits a reflex stimulation of vagal efferent activity sufficient to cause bronchoconstriction in asthmatic rats. Here, we show that pathophysiological concentrations of asthma-associated prototypical Th2 cytokines also stimulate the carotid bodies. Stimulation of the carotid bodies by these asthmakines involves a PKCε-transient receptor potential vanilloid 1 (TRPV1) signalling mechanism likely dependent on TRPV1 S502 and T704 phosphorylation sites.

Intestinal fungi are causally implicated in microbiome assembly and immune development in mice.

The gut microbiome consists of a multi-kingdom microbial community. Whilst the role of bacteria as causal contributors governing host physiological development is well established, the role of fungi remains to be determined. Here, we use germ-free mice colonized with defined species of bacteria, fungi, or both to differentiate the causal role of fungi on microbiome assembly, immune development, susceptibility to colitis, and airway inflammation.

Functional-Optical Coherence Tomography: A Non-invasive Approach to Assess the Sympathetic Nervous System and Intrinsic Vascular Regulation.

Sympathetic nervous system dysregulation and vascular impairment in neuronal tissue beds are hallmarks of prominent cardiorespiratory diseases. However, an accurate and convenient method of assessing SNA and local vascular regulation is lacking, hindering routine clinical and research assessments. To address this, we investigated whether spectral domain optical coherence tomography (OCT), that allows investigation of retina and choroid vascular responsiveness, reflects sympathetic activity in order to develop a quick, easy and non-invasive sympathetic index.

The Role of Airway Myofibroblasts in Asthma.

Airway remodeling is a characteristic feature of asthma and is thought to play an important role in the pathogenesis of airway hyperresponsiveness. Myofibroblasts are key structural cells involved in injury and repair, and there is evidence that dysregulation of their normal function contributes to airway remodeling. Despite the importance of myofibroblasts, a lack of specific cellular markers and inconsistent nomenclature have limited recognition of their key role in airway remodeling.

Preventing acute asthmatic symptoms by targeting a neuronal mechanism involving carotid body lysophosphatidic acid receptors.

Asthma accounts for 380,000 deaths a year. Carotid body denervation has been shown to have a profound effect on airway hyper-responsiveness in animal models but a mechanistic explanation is lacking. Here we demonstrate, using a rat model of asthma (OVA-sensitized), that carotid body activation during airborne allergic provocation is caused by systemic release of lysophosphatidic acid (LPA).

Hindlimb unweighting does not alter vasoconstrictor responsiveness and nitric oxide-mediated inhibition of sympathetic vasoconstriction.

Key Points: Physical inactivity increases the risk of cardiovascular disease and may alter sympathetic nervous system control of vascular resistance. Hindlimb unweighting (HU), a rodent model of physical inactivity, has been shown to diminish sympathetic vasoconstrictor responsiveness and reduce NO synthase expression in isolated skeletal muscle blood vessels. Our understanding of the effects of HU on sympathetic vascular regulation in vivo is very limited.

Acute tetrahydrobiopterin supplementation attenuates sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle of healthy rats.

Tetrahydrobiopterin (BH4) is an essential cofactor for the production of nitric oxide (NO) and supplementation with BH4 improves NO-dependent vasodilation. NO also reduces sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle. Thus, we hypothesized that supplementation with BH4 would blunt sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle.

Exercise training augments neuronal nitric oxide synthase-mediated inhibition of sympathetic vasoconstriction in contracting skeletal muscle of rats.

We tested the hypothesis that exercise training would increase neuronal nitric oxide synthase (nNOS)-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Sprague-Dawley rats (n = 18) were randomized to sedentary or exercise-trained (40 m min(-1), 5° grade; 5 days week(-1) for 4 weeks) groups. Following completion of sedentary behaviour or exercise training, rats were anaesthetized and instrumented with a brachial artery catheter, femoral artery flow probe and stimulating electrodes on the lumbar sympathetic chain.

Short-term exercise training augments 2-adrenoreceptor-mediated sympathetic vasoconstriction in resting and contracting skeletal muscle.

We hypothesized that exercise training (ET) would alter α2-adrenoreceptor-mediated sympathetic vasoconstriction. Sprague-Dawley rats (n = 30) were randomized to sedentary (S), mild- (M) or heavy-intensity (H) treadmill ET groups (5 days per week for 4 weeks). Following the ET component of the study, rats were anaesthetized, and instrumented for lumbar sympathetic chain stimulation, triceps surae muscle contraction and measurement of femoral vascular conductance (FVC).

Role of neuronal nitric oxide in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats.

Isoform-specific nitric oxide (NO) synthase (NOS) contributions to NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle are incompletely understood. The purpose of the present study was to investigate the role of neuronal NOS (nNOS) in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats. We hypothesized that acute pharmacological inhibition of nNOS would augment sympathetic vasoconstriction in resting and contracting skeletal muscle, demonstrating that nNOS is primarily responsible for NO-mediated inhibition of sympathetic vasoconstriction.

Acute superoxide scavenging reduces sympathetic vasoconstrictor responsiveness in short-term exercise-trained rats.

We hypothesized that acute superoxide (O2(-)) scavenging would attenuate sympathetic vasoconstrictor responsiveness by augmenting nitric oxide (NO)-mediated inhibition of sympathetic vasoconstriction in exercise-trained rats. Sprague-Dawley rats were randomly assigned to sedentary time control (S; n = 7) or mild- (M: 20 m/min, 5° grade; n = 7) or heavy-intensity (H: 40 m/min, 5° grade; n = 7) exercise training (ET) groups and trained 5 days/wk for 4 wk with matched training volume. Following ET, rats were anesthetized and instrumented for lumbar sympathetic chain stimulation and measurement of femoral vascular conductance.

Short-term exercise training enhances functional sympatholysis through a nitric oxide-dependent mechanism.

We tested the hypothesis that short-term mild- (M) and heavy-intensity (H) exercise training would enhance sympatholysis through a nitric oxide (NO)-dependent mechanism. Sprague-Dawley rats (n = 36) were randomly assigned to sedentary (S) or to M (20 m min(-1) 5% gradient) or H exercise training groups (40 m min(-1) 5% gradient). Rats assigned to M and H groups trained on 5 days week(-1) for 4 weeks, with the volume of training being matched between groups.

Short-term exercise training augments sympathetic vasoconstrictor responsiveness and endothelium-dependent vasodilation in resting skeletal muscle.

We tested the hypotheses that 4 wk of exercise training would diminish the magnitude of vasoconstriction in response to sympathetic nerve stimulation and augment endothelium-dependent vasodilation (EDD) in resting skeletal muscle in a training intensity-dependent manner. Sprague-Dawley rats were randomly assigned to sedentary time-control (S), mild- (M; 20 m/min, 5% grade), or heavy-intensity (H; 40 m/min, 5% grade) treadmill exercise groups. Animals trained 5 days/wk for 4 wk with training volume matched between groups.

Using Telehealth technology to deliver pulmonary rehabilitation in chronic obstructive pulmonary disease patients.

Background: Pulmonary rehabilitation (PR) is an effective therapeutic strategy to improve health outcomes in patients with chronic obstructive pulmonary disease (COPD); however, there is insufficient PR capacity to service all COPD patients, thus necessitating creative solutions to increase the availability of PR.

Objective: To examine the efficacy of PR delivered via Telehealth (Telehealth-PR) compared with PR delivered in person through a standard outpatient hospital-based program (Standard-PR).

Methods: One hundred forty-seven COPD patients participated in an eight-week rural PR program delivered via Telehealth-PR.

A prospective evaluation of non-interval- and interval-based exercise training progressions in rodents.

Non-interval and interval training progressions were used to determine (i) the mean rate at which treadmill speed could be incremented daily using a non-interval training progression to train rats to run continuously at different intensities and (ii) the number of training days required for rats to run continuously at different exercise intensities with non-interval- and interval-based training progressions to establish methods of progressive overload for rodent exercise training studies. Rats were randomly assigned to mild-intensity (n = 5, 20 m·min(-1), 5% grade), moderate-intensity (n = 5, 30 m·min(-1), 5% grade), and heavy-intensity non-interval groups (n = 5, 40 m·min(-1), 5% grade) or a heavy-intensity interval (n = 5, 40 m·min(-1), 5% grade) group and ran 5 days·week(-1) for 6 weeks. Non-interval training involved a daily increase of treadmill speed, whereas interval training involved a daily increase of interval time, until the animal could run continuously at a prescribed intensity.

Pulmonary oxygen uptake and heart rate kinetics during the six-minute walk test in transplant recipients.

Background: The effect of organ transplantation on arterial compliance, pulmonary oxygen uptake (VO2p) and heart rate kinetics during the 6-minute walk test (6-MWT) remains unknown.

Methods: Twenty-two thoracic (heart and/or lung) organ transplant recipients (TOTR, 51+/-12 years) and 30 abdominal (kidney, kidney-pancreas, or liver) organ transplant recipients (AOTR, 46+/-11 years) from the 2006 Canadian Transplant Games, and 37 healthy controls (HC) completed a 6-MWT. VO2p, heart rate kinetics, and arterial compliance were determined.