Search

Background Spinal cord injury (SCI) is associated with an increased risk and prevalence of cardiopulmonary and cerebrovascular disease-related morbidity and mortality. The factors that initiate, promote, and accelerate vascular diseases and events in SCI are poorly understood. Clinical interest in circulating endothelial cell-derived microvesicles (EMVs) and their microRNA (miRNA) cargo has intensified due to their involvement in endothelial dysfunction, atherosclerosis, and cerebrovascular events. Objectives The aim of this study was to determine whether a subset of vascular-related miRNAs is differentially expressed in EMVs isolated from adults with SCI. Methods We assessed eight adults with tetraplegia (7 male/1 female; age: 46±4 years; time since injury: 26±5 years) and eight uninjured (6 male/2 female; age: 39±3 years). Circulating EMVs were isolated, enumerated, and collected from plasma by flow cytometry. The expression of vascular-related miRNAs in EMVs was assessed by RT-PCR. Results Circulating EMV levels were significantly higher (~130%) in adults with SCI compared with uninjured adults. The expression profile of miRNAs in EMVs from adults with SCI were significantly different than uninjured adults and were pathologic in nature. Expression of miR-126, miR-132, and miR-Let-7a were lower (~100–150%; p < .05), whereas miR-30a, miR-145, miR-155, and miR-216 were higher (~125–450%; p < .05) in EMVs from adults with SCI. Conclusion This study is the first examination of EMV miRNA cargo in adults with SCI. The cargo signature of vascular-related miRNAs studied reflects a pathogenic EMV phenotype prone to induce inflammation, atherosclerosis, and vascular dysfunction. EMVs and their miRNA cargo represent a novel biomarker of vascular risk and a potential target for intervention to alleviate vascular-related disease after SCI.

In this case study, we evaluate the unique physiological profiles of two world-champion breath-hold divers. At close to current world- record depths, the extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure are profound. As such, these professional athletes must be capable of managing such stress, to maintain performing at the forefront human capacity. In both divers, pulmonary function before and after deep dives to 102 m and 117 m in the open sea was assessed using noninvasive pulmonary gas exchange (indexed via the O-2 deficit, which is analogous to the traditional alveolar to arterial oxygen difference), ultrasound B-line scores, airway resistance, and airway reactance. Hydrostatic- induced lung compression was also quantified via spirometry. Both divers successfully performed their dives. Pulmonary gas exchange efficiency was impaired in both divers at 10 min but had mostly restored within a few hours. Mild hemoptysis was transiently evident immediately following the 117- m dive, whereas both divers experienced nitrogen narcosis. Although B-lines were only elevated in one diver postdive, reductions in airway resistance and reactance occurred in both divers, suggesting that the compressive strain on the structural characteristics of the airways can persist for up to 3.5 h. Marked echocardiographic dyssynchrony was evident in one diver after 10 m of descent, which persisted until resolving at similar to 77m during ascent. In summary, despite the enormous hydrostatic and physiological stress to diving beyond 100 m on a single breath, these data provide valuable insight into the extraordinary capacity of those at the pinnacle of apneic performance. NEW & NOTEWORTHY This study shows that world-champion breath-hold divers demonstrate incredible tolerability to extreme levels of hydrostatic-induced lung compression. Immediately following dives to >100 m, there were acute impairments in pulmonary gas exchange efficiency, mild accummulation of extravascular lung fluid, noticable intrathoracic discomfort, and evident nitrogen narcosis, however, within a few hours, these had all mostly resolved.

New findings What is the central question of this study? What are the characteristics of cerebral blood flow (CBF) regulation following a single SCUBA dive to a depth of 18 m sea water with a 47 min bottom time. What is the main finding and its importance? Acute alterations in CBF regulation at rest, including extra-cranial vasodilatation, reductions in shear patterns and elevations in intra-cranial blood velocity were observed at rest following a single SCUBA dive. These subtle changes in CBF regulation did not translate into any functional changes in cerebrovascular reactivity to hypoxia or hyperoxia, or neurovascular coupling following a single SCUBA dive. Abstract Reductions in vascular function during a SCUBA dive - due to hyperoxia-induced oxidative stress, arterial and venous gas emboli and altered endothelial integrity - may also extend to the cerebrovasculature following return to the surface. This study aimed to characterize cerebral blood flow (CBF) regulation following a single SCUBA dive to a depth of 18 m sea water with a 47 min bottom time. Prior to and following the dive, participants (n = 11) completed (1) resting CBF in the internal carotid (ICA) and vertebral (VA) arteries (duplex ultrasound) and intra-cranial blood velocity (v) of the middle and posterior cerebral arteries (MCAv and PCAv, respectively) (transcranial Doppler ultrasound); (2) cerebrovascular reactivity to acute poikilocapnic hypoxia (i.e. F I O 2 , 0.10) and hyperoxia (i.e. F I O 2 , 1.0); and (3) neurovascular coupling (NVC; regional CBF response to local increases in cerebral metabolism). Global CBF, cerebrovascular reactivity to hypoxia and hyperoxia, and NVC were unaltered following a SCUBA dive (all P > 0.05); however, there were subtle changes in other cerebrovascular metrics post-dive, including reductions in ICA (-13 ± 8%, P = 0.003) and VA (-11 ± 14%, P = 0.021) shear rate, lower ICAv (-10 ± 9%, P = 0.008) and VAv (-9 ± 14%, P = 0.028), increases in ICA diameter (+4 ± 5%, P = 0.017) and elevations in PCAv (+10 ± 19%, P = 0.047). Although we observed subtle alterations in CBF regulation at rest, these changes did not translate into any functional changes in cerebrovascular reactivity to hypoxia or hyperoxia, or NVC. Whether prolonged exposure to hyperoxia and hyperbaria during longer, deeper, colder and/or repetitive SCUBA dives would provoke changes to the cerebrovasculature requires further investigation.

Voluntary asphyxia imposed by static apnea challenges blood-brain barrier (BBB) integrity in humans through transient extremes of hypertension, hypoxemia and hypercapnia. In the present study, ten ultra-elite breath-hold divers performed two maximal dry apneas preceded by normoxic normoventilation (NX: severe hypoxemia and hypercapnia) and hyperoxic hyperventilation (HX: absence of hypoxemia with exacerbating hypercapnia) with measurements obtained before and immediately after apnea. Transcerebral exchange of NVU proteins (ELISA, Single Molecule Array) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial to internal jugular venous concentration gradients. Apnea duration increased from 5 m 6 s in NX to 15 m 59 s in HX ( P =

Cervical spinal cord injury (SCI) leads to autonomic cardiovascular dysfunction that underlies the three- to fourfold elevated risk of cardiovascular disease in this population. Reduced common carotid artery (CCA) dilatory responsiveness during the cold-pressor test (CPT) is associated with greater cardiovascular disease risk and progression. The cardiovascular and CCA responses to the CPT may provide insight into cardiovascular autonomic dysfunction and cardiovascular disease risk in individuals with cervical SCI. Here, we used CPT to perturb the autonomic nervous system in 14 individuals with cervical SCI and 12 uninjured controls, while measuring cardiovascular responses and CCA diameter. The CCA diameter responses were 55% impaired in those with SCI compared with uninjured controls (P = 0.019). The CCA flow, velocity, and shear response to CPT were reduced in SCI by 100% (P < 0.001), 113% (P = 0.001), and 125% (P = 0.002), respectively. The association between mean arterial pressure and CCA dilation observed in uninjured individuals (r = 0.54, P = 0.004) was absent in the SCI group (r = 0.22, P = 0.217). Steady-state systolic blood pressure (P = 0.020), heart rate (P = 0.003), and cardiac contractility (P < 0.001) were reduced in those with cervical SCI, whereas total peripheral resistance was increased compared with uninjured controls (P = 0.042). Relative cerebral blood velocity responses to CPT were increased in the SCI group and reduced in controls (middle cerebral artery, P = 0.010 ; posterior cerebral artery, P = 0.026). The CCA and cardiovascular responsiveness to CPT are impaired in those with cervical SCI.NEW & NOTEWORTHY This is the first study demonstrating that CCA responses during CPT are suppressed in SCI. Specifically, CCA diameter, flow, velocity, and shear rate were reduced. The relationship between changes in MAP and CCA dilatation in response to CPT was absent in individuals with SCI, despite similar cardiovascular activation between SCI and uninjured controls. These findings support the notion of elevated cardiovascular disease risk in SCI and that the cardiovascular responses to environmental stimuli are impaired.

Individuals with cervical spinal cord injury (SCI) are at an increased risk for cardiovascular disease. Exercise is well-established for preventing cardiovascular disease; however, there are limited straightforward and safe exercise approaches for increasing the activity of the cardiorespiratory system after cervical SCI. The objective of this study was to investigate the cardiorespiratory response to passive leg cycling in people with cervical SCI. Beat-by-beat blood pressure, heart rate, and cerebral blood flow were measured before and throughout 10 minutes of cycling in 11 people with SCI. Femoral artery flow-mediated dilation was also assessed before and immediately after passive cycling. Safety was monitored throughout all study visits. Passive cycling elevated systolic blood pressure (5 ± 2 mm Hg), mean arterial pressure (5 ± 3 mm Hg), stroke volume (2.4 ± 0.8 mL), heart rate (2 ± 1 beats/min) and cardiac output (0.3 ± 0.07 L/min; all p < 0.05). Minute ventilation (0.67 ± 0.23 L/min), tidal volume (70 ± 30 mL) and end-tidal PO2 (2.6 ± 1.23 mm Hg) also increased (all p < 0.05). Endothelial function was improved immediately after exercise (1.62 ± 0.13%, p < 0.01). Passive cycling resulted in an incidence of autonomic dysreflexia. Therefore, passive leg cycling increased the activity of the cardiorespiratory system and improved endothelial function, indicating it may be a beneficial exercise intervention for the cardiovascular and respiratory systems in people with cervical SCI. Novelty: Passive leg cycling increases the activity of the cardiorespiratory system and improves markers of cardiovascular health in cervical SCI. Passive leg cycling exercise is an effective, low-cost, practical, alternative exercise modality for people with cervical SCI.

ObjectiveTo determine the population-level odds of individuals with spinal cord injury (SCI) experiencing fatigue and sleep apnea, to elucidate relationships with level and severity of injury, and to examine associations with abnormal cerebrovascular responsiveness.MethodsWe used population-level data, meta-analyses, and primary physiologic assessments to provide a large-scale integrated assessment of sleep-related complications after SCI. Population-level and meta-analyses included more than 60,000 able-bodied individuals and more than 1,800 individuals with SCI. Physiologic assessments were completed on a homogenous sample of individuals with cervical SCI and matched controls. We examined the prevalence of (1) self-reported chronic fatigue, (2) clinically identified sleep apnea, and 3) cerebrovascular responsiveness to changing CO2.ResultsLogistic regression revealed a 7-fold elevated odds of chronic fatigue after SCI (odds ratio [OR] 7.9, 95% confidence interval [CI] 3.5–16.2), and that fatigue and trouble sleeping are correlated with the level and severity of injury. We further show that those with SCI experience elevated risk of clinically defined sleep-disordered breathing in more than 600 individuals with SCI (pooled OR 3.1, 95% CI 1.3–7.5). We confirmed that individuals with SCI experience a high rate of clinically defined sleep apnea using primary polysomnography assessments. We then provide evidence using syndromic analysis that sleep-disordered breathing is a factor strongly associated with impaired cerebrovascular responsiveness to CO2 in patients with SCI.ConclusionsIndividuals with SCI have an increased prevalence of sleep-disordered breathing, which may partially underpin their increased risk of stroke. There is thus a need to integrate sleep-related breathing examinations into routine care for individuals with SCI.

Study design Experimental study. Objectives Compromised cerebrovascular function likely contributes to elevated neurological risk in spinal cord injury (SCI). Passive heating offers many cardiovascular and neurological health benefits ; therefore, we aimed to determine the effects of an acute bout of heating on cerebrovascular function in chronic SCI. Methods Persons with cervical SCI (n = 15) and uninjured controls (CON ; n = 15) completed 60 min of lower limb hot water immersion (40 degrees C). Assessments of middle cerebral (MCA) and posterior cerebral artery (PCA) velocities, pulsatilities, and neurovascular coupling (NVC) were performed using transcranial Doppler ultrasound. Duplex ultrasonography was used to index cerebral blood flow via the internal carotid artery (ICA), and carotid-femoral pulse-wave velocity (PWV) was measured using tonometry. The NVC response was quantified as the peak hyperemic value during 30-s cycles of visual stimulation. Results Mean arterial pressure changed differentially with heating [mean (standard deviation) ; SCI: +6(14) mmHg, CON: -8(12) mmHg ; P = 0 .01]. There were no differences in any intracranial artery measures (all P > 0.05), except for small (similar to 10%) increases in MCA conductance in CON after heating vs. SCI (interaction P = 0.006). Resting ICA flow was greater in SCI vs. CON (P = 0.03) but did not change with heating in either group (interaction P = 0.34). There were also no between-group differences in the NVC response (Delta PCA conductance) pre- [SCI: 29(19)% vs. CON: 30(9)%] or post-heating [SCI 30(9)% vs. 25(9)% ; interaction P = 0.22]. Conclusions Mild acute heating does not impair or improve cerebrovascular function in SCI or CON. Thus, further study of the effects of chronic heating interventions are warranted.

Background The aim of this international study was to investigate the prevalence of the use of sports supplements among young athletes, as well as their knowledge and attitudes towards sports supplementation. Methods Organized survey study testing the level of knowledge, attitudes, beliefs and practices concerning the use of sports supplements was administered to 348 athletes, 15–18 year olds from 4 countries competing in 18 sports at the international level. Results The prevalence rate of the intake of sports supplements was 82.2%, with the protein supplements being predominant (54.5%). Coaches were identified as the primary source of information regarding supplementation (41.4%). The enhancement of athletic performance (35.4%) was the major motivation for the supplements intake. The majority of athletes (72.1%) were aware of associated health risks. The young athletes possess varying levels of knowledge regarding their own supplementation. The obtained data about the level of knowledge were statistically analyzed using the correspondence analysis. Less than 40% of athletes had the knowledge about the proper and intended use of protein, creatine, amino acids, beta alanine and glutamine, while they had greater understanding about vitamins and minerals, sports drinks and caffeine. The athletes in developed countries had greater access and utilization of professional resources such as dieticians. Young athletes are still unfamiliar with WADA regulations (55.5%), and the misuse of sports supplements represents an ethical dilemma for some. Conclusion These findings indicate the necessity of a comprehensive education of all team members about sports supplements and careful supervision of the athletic development of young athletes. Electronic supplementary material The online version of this article (10.1186/s12970-019-0294-7) contains supplementary material, which is available to authorized users.

The relationship between aging and changes in heart rate variability (HRV) could depend on the metabolic profile of obese people, i.e. metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). We aimed to determine the age at which obesity related autonomic dysfunction becomes significant and whether it decreases differently according to metabolic profile. We analyzed HRV in 99 adults using Wildman’s criteria for metabolic profile and 5-minute HRV for autonomic nervous system. In MHO, high frequency (HF) decreased in the 4th decade of life. In MUO, standard deviation of R-R intervals (SDNN), root mean square of successive differences of all R-R intervals (RMSSD), number of adjacent intervals differing by more than 50 ms expressed as percentage of all intervals in the collecting period (pNN50), HF, low frequency (LF), LF/HF (LF divided by HF) and total power (TP) decreased in the 4th decade of life (partial shared variance 28%-36%). In conclusion, an age dependent decrease of HRV occurs in MUO between the third and fifth decade of life. In MHO, HF significantly decreases around the age of 40 years. Cardiometabolic profile influences metabolic aging, altering the autonomic nervous system., Dobne promjene u varijabilnosti srčane frekvencije (HRV) mogu zavisiti o metaboličkom profilu pretilih osoba, tj. metaboličkin zdrave (MHO) i metabolički rizične pretile osobe (MUO). Željeli smo utvrditi dob u kojoj nastupa autonomna disfunkcija povezana s pretilošću te opada li HRV različito kod osoba različitog metaboličkog profila. Analizirali smo HRV kod 99 odraslih osoba uz primjenu Wildmanovih kriterija metaboličkog profila i HRV kao aktivnosti autonomnog živčanog sustava. Kod MHO, visoka frekvencija (HF) opadala je u 4. desetljeću života. Kod MUO su standardna devijacija svih R-R intervala (SDNN), kvadratni korijen srednje razlike između sukcesivnih normalnih R-R intevala (RMSSD), postotak sukcesivnih R-R intervala vrijednost kojih prelazi 50 ms (pNN50), HF, niska frekvencija (LF), omjer LF i HF (LF/HF) i ukupna spektralna snaga (TP) opadali u 4. desetljeću života (parcijalna podijeljena varijanca 28%-36%). U zaključku, utvrđen je od dobi zavisan pad HRV kod MUO između trećeg i petog desetljeća života. Kod MHO osoba HF je značajno opala oko 40. godine života. Kardiometabolički profil utječe na starenje remeteći funkcije autonomnog živčanog sustava.

New Findings What is the central question of this study? How does deep breath-hold diving impact cardiopulmonary function, both acutely and over the subsequent 2.5 hours post-dive? What is the main finding and its importance? Breath-hold diving, to depths below residual volume, is associated with acute impairments in pulmonary gas exchange, which typically resolve within 2.5 hours. These data provide new insight into the behaviour of the lungs and pulmonary vasculature following deep diving. Breath-hold diving involves highly integrative and extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure. Over two diving training camps (Study 1 and 2), 25 breath-hold divers (recreational to world- champion) performed 66 dives to 57 +/- 20 m (range: 18-117 m). Using the deepest dive from each diver, temporal changes in cardiopulmonary function were assessed using non-invasive pulmonary gas exchange (indexed via the O-2 deficit), ultrasound B-line scores, lung compliance and pulmonary haemodynamics at baseline and following the dive. Hydrostatically induced lung compression was quantified in Study 2, using spirometry and lung volume measurement, enabling each dive to be categorized by its residual volume (RV)-equivalent depth. From both studies, pulmonary gas exchange inefficiency - defined as an increase in O-2 deficit - was related to the depth of the dive (r(2 )= 0.345 ; P < 0.001), with dives associated with lung squeeze symptoms exhibiting the greatest deficits. In Study 1, although B-lines doubled from baseline (P = 0.027), cardiac output and pulmonary artery systolic pressure were unchanged post-dive. In Study 2, dives with lung compression to

The pathogenesis of predominantly neurological decompression sickness (DCS) is multifactorial. In SCUBA diving, besides gas bubbles, DCS has been linked to microparticle release, impaired endothelial function, and platelet activation. This study focused on vascular damage and its potential role in the genesis of DCS in breath-hold diving. Eleven breath-hold divers participated in a field study comprising eight deep breath-hold dives with short surface periods and repetitive breath-hold dives lasting for 6 h. Endothelium-dependent vasodilation of the brachial artery, via flow-mediated dilation (FMD), and the number of microparticles (MPs) were assessed before and after each protocol. All measures were analyzed by two-way within-subject ANOVA (2 × 2 ANOVA; factors: time and protocol). Absolute FMD was reduced following both diving protocols (p < 0.001), with no interaction (p = 0.288) or main effect of protocol (p = 0.151). There was a significant difference in the total number of circulating MPs between protocols (p = 0.007), where both increased post-dive (p = 0.012). The number of CD31+/CD41– and CD66b+ MP subtypes, although different between protocols (p < 0.001), also increased by 41.0% ± 56.6% (p = 0.050) and 60.0% ± 53.2% (p = 0.045) following deep and repetitive breath-hold dives, respectively. Both deep and repetitive breath-hold diving lead to endothelial dysfunction that may play an important role in the genesis of neurological DCS.

Intimate communication between neural and vascular structures is required to match neuronal metabolism to blood flow, a process termed neurovascular coupling. The number of laboratories assessing neurovascular coupling in humans is increasing due to clinical interest in disease states, and basic science interest in a non-anesthetized, non-craniotomized, unrestrained, in vivo model. However, there is a lack of knowledge regarding how best to characterize the neurovascular response. To address this knowledge gap, we have amassed a highly powered human neurovascular coupling dataset, and deployed a network-based approach to reveal the most powerful and consistent metrics for quantifying neurovascular coupling. Using dimensionality reduction, community-based clustering, and majority-voting of traditional metrics (e.g. peak response, time to peak) and non-traditional metrics (e.g. varying time windows, pulsatility), we have identified which of the existing metrics predominantly characterize the neurovascular coupling response, are stable within and across participants, and explain the vast majority of the variance within our dataset of over 300 trials. We then harnessed our empirical approach to generate powerful novel metrics of neurovascular coupling, termed iAmplitude, iRate, and iPulsatility, which increase sensitivity when capturing population differences. These metrics may be useful to optimally understand neurovascular coupling in health and disease.

This article was published in Experimental Physiology on 01 August 2017, available at http://dx.doi.org/10.1113/EP086429

OBJECTIVES: We determined whether stroke and/or TIA subjects have exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) and/or patent foramen ovale (QPFO ) and a genetic predisposition for ischemic stroke. METHODS: Twenty-eight stroke and/or TIA subjects (33-63 years old) underwent transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect QIPAVA and QPFO at rest and during supine exercise with and without breathing 100% O2 . We also examined genetic polymorphisms in FV Leiden (G1691A ; rs6025), factor II (FII) prothrombin (G20210A ; rs1799963), methylene tetrahydfropholate reductase (C677T, rs1801133), and plasminogen- activator inhibitor-1 (PAI-1) (4G/5G ; rs1799889) and angiotensin-converting enzyme (ACE ; I/D, rs4646994) in 24/28 subjects. RESULTS: No subject without PFO had QIPAVA at rest (n=17), but 12/17 did with exercise. All PFO subjects had QPFO at rest (n=11) and 7/11 had either QIPAVA or QPFO with exercise. Breathing 100% O2 during exercise reduced or eliminated left heart contrast in all subjects. Gene analyses revealed that 15/24 patients were either heterozygous or homozygous for methylenetetrahydrofolate reductase gene polymorphism ; 4G/4G and 4G/5G genotypes of plasminogen-activator inhibitor-1 were present in 7/24 and 13/24 patients, respectively ; polymorphisms of ACE D/D genotype were present in 6/24 and I/D in 14/24 patients. Having both I/D and 4G/4G genotypes was more prevalent in PFO+ subjects (P=.03), and there was a trend (P=.06) for PFO- subjects to have a greater D/D genotype prevalence. CONCLUSIONS: Novel genetic predispositions reported here in PFO subjects should be investigated further in larger stroke and/or TIA patient datasets.

Mitochondria are ubiquitous organelles of eukaryotic cells and they are the mayor site of generating energy in the form of adenosine triphoshate through the process of oxidative phosphorylation. Analysis and estimation of mitochondrial function is of outmost importance when it comes to studying intracellular energy metabolism, mechanisms of apoptosis, signaling pathways, calcium storage and the pathophysiology of a large spectrum of human diseases including various neurodegenerative diseases, myopathies, metabolic syndromes and cancer. Respiratory capacity analysis covers one of the many roles that mitochondria play in living cells and it provides us with useful data about functional integrity of mitochondria. Assessment of individual respiratory chain complexes or other mitochondrial enzymes has been widely used to estimate mitochondrial function and dysfunction but it neglects the influence of complex structural and functional interplay of mitochondrial proteins and enzymes and plasmic compounds. Another method that emphasises the importance of studying intact mitochondria is in vitro technique, and although it has many advantages, in some aspects it is far from being representative when it comes to functional assessment of mitochondria. From the perspective of energy production and consumption, the cardiac muscle is a highly demanding tissue and it is the well functioning of mitochondria that is conditio sine qua non for this nature to be fulfilled. In cooperation with the University of Split School of Medicine in Split and under the mentorship of Prof. Marko Ljubkovic, the Department of Physiology of the Faculty of Medicine Novi Sad works on introducing in situ approaches in the analysis of respiratory mitochondrial function in skinned muscle fibers of human cardiac tissue.

Breath-hold divers (BHD) experience repeated bouts of severe hypoxia and hypercapnia with large increases in blood pressure. However, the impact of long-term breath-hold diving on cerebrovascular control remains poorly understood. The ability of cerebral blood vessels to respond rapidly to changes in blood pressure represents the property of dynamic autoregulation. The current investigation tested the hypothesis that breath-hold diving impairs dynamic autoregulation to a transient hypotensive stimulus. Seventeen BHD (3 women, 11 ± 9 yr of diving) and 15 healthy controls (2 women) completed two or three repeated sit-to-stand trials during spontaneous breathing and poikilocapnic conditions. Heart rate (HR), finger arterial blood pressure (BP), and cerebral blood flow velocity (BFV) from the right middle cerebral artery were measured continuously with three-lead electrocardiography, finger photoplethysmography, and transcranial Doppler ultrasonography, respectively. End-tidal carbon dioxide partial pressure was measured with a gas analyzer. Offline, an index of cerebrovascular resistance (CVRi) was calculated as the quotient of mean BP and BFV. The rate of the drop in CVRi relative to the change in BP provided the rate of regulation [RoR; (∆CVRi/∆T)/∆BP]. The BHD demonstrated slower RoR than controls ( P ≤ 0.001, d = 1.4). Underlying the reduced RoR in BHD was a longer time to reach nadir CVRi compared with controls ( P = 0.004, d = 1.1). In concert with the longer CVRi response, the time to reach peak BFV following standing was longer in BHD than controls ( P = 0.01, d = 0.9). The data suggest impaired dynamic autoregulatory mechanisms to hypotension in BHD. NEW & NOTEWORTHY Impairments in dynamic cerebral autoregulation to hypotension are associated with breath-hold diving. Although weakened autoregulation was observed acutely in this group during apneic stress, we are the first to report on chronic adaptations in cerebral autoregulation. Impaired vasomotor responses underlie the reduced rate of regulation, wherein breath-hold divers demonstrate a prolonged dilatory response to transient hypotension. The slower cerebral vasodilation produces a longer perturbation in cerebral blood flow velocity, increasing the risk of cerebral ischemia.

What is the central question of this study? Do individuals with chronic obstructive pulmonary disease have blood flow through intrapulmonary arteriovenous anastomoses at rest or during exercise? What is the main finding and its importance? Individuals with chronic obstructive pulmonary disease have a greater prevalence of blood flow through intrapulmonary arteriovenous anastomoses at rest than age-matched control subjects. Given that the intrapulmonary arteriovenous anastomoses are large enough to permit venous emboli to pass into the arterial circulation, patients with chronic obstructive pulmonary disease and an elevated risk of thrombus formation may be at risk of intrapulmonary arteriovenous anastomosis-facilitated embolic injury (e.g. stroke or transient ischaemic attack). The pulmonary capillaries prevent stroke by filtering venous emboli from the circulation. Intrapulmonary arteriovenous anastomoses are large-diameter (≥50 μm) vascular connections in the lung that may compromise the integrity of the pulmonary capillary filter and have recently been linked to cryptogenic stroke and transient ischaemic attack. Prothrombotic populations, such as individuals with chronic obstructive pulmonary disease (COPD), may be at increased risk of stroke and transient ischaemic attack facilitated by intrapulmonary arteriovenous anastomoses, but the prevalence and degree of blood flow through intrapulmonary arteriovenous anastomoses in this population has not been fully examined and compared with age-matched healthy control subjects. We used saline contrast echocardiography to assess blood flow through intrapulmonary arteriovenous anastomoses at rest (n = 29 COPD and 19 control subjects) and during exercise (n = 10 COPD and 10 control subjects) in subjects with COPD and age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses was detected in 23% of subjects with COPD at rest and was significantly higher compared with age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses at rest was reduced or eliminated in subjects with COPD after breathing hyperoxic gas. Sixty per cent of subjects with COPD who did not have blood flow through the intrapulmonary arteriovenous anastomoses at rest had blood flow through them during exercise. The combination of blood flow through intrapulmonary arteriovenous anastomoses and potential for thrombus formation in individuals with COPD may permit venous emboli to pass into the arterial circulation and cause stroke and transient ischaemic attack. Breathing supplemental oxygen may reduce this risk in COPD. The link between blood flow through intrapulmonary arteriovenous anastomoses, stroke and transient ischaemic attack is worthy of future investigation in COPD and other populations.

This article was published in Journal of Physiology on 3 June 2016 (online). The definitive version of record is available at http://dx.doi.org/10.1113/JP272404

International audience

NEW FINDINGS What is the central question of this study? Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation

Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunction in SCI and the acute effects of passive heating. Fifteen participants with cervical SCI and 15 uninjured control (CON) participants underwent ultrasound assessments of vascular function and venous blood sampling for biomarkers of endothelial activation (i.e., CD62e+) and apoptosis (i.e., CD31+/42b−) before and after a 60-min exposure to lower limb hot water immersion (40°C). In SCI, macrovascular endothelial function was reduced in the brachial artery [SCI: 4.8 (3.2)% vs. CON: 7.6 (3.4)%, P = 0.04] but not the femoral artery [SCI: 3.7 (2.6)% vs. CON: 4.0 (2.1)%, P = 0.70]. Microvascular function, via reactive hyperemia, was ~40% lower in SCI versus CON in both the femoral and brachial arteries ( P < 0.01). Circulating concentrations of CD62e+ were elevated in SCI versus CON [SCI: 152 (106) microparticles/µl vs. CON: 58 (24) microparticles/µl, P < 0.05]. In response to heating, macrovascular and microvascular function remained unchanged, whereas increases (+83%) and decreases (−93%) in antegrade and retrograde shear rates, respectively, were associated with heat-induced reductions of CD62e+ concentrations in SCI to levels similar to CON ( P = 0.05). These data highlight the potential of acute heating to provide a safe and practical strategy to improve vascular function in SCI. The chronic effects of controlled heating warrant long-term testing. NEW & NOTEWORTHY Individuals with cervical level spinal cord injury exhibit selectively lower flow-mediated dilation in the brachial but not femoral artery, whereas peak reactive hyperemia was lower in both arteries compared with uninjured controls. After 60 min of lower limb hot water immersion, femoral artery blood flow and shear patterns were acutely improved in both groups. Elevated biomarkers of endothelial activation in the spinal cord injury group decreased with heating, but these biomarkers remained unchanged in controls.

The capacity of the cerebrovasculature to buffer changes in blood pressure (BP) likely plays an important role in the prevention of stroke, which is three- to fourfold more common after spinal cord injury (SCI). Although the directional relationship between BP and cerebral blood flow (CBF) has traditionally been thought to travel solely from BP to CBF, a Cushing-like mechanism functioning in the inverse direction, in which changes in CBF influence BP, has recently been revealed using Granger causality analysis. Although both CBF buffering of BP and the Cushing- like mechanism are influenced by the sympathetic nervous system, we do not understand the impact of disruption of descending sympathetic pathways within the spinal cord, caused by cervical SCI on these regulatory systems. We hypothesized that people with cervical SCI would have greater BP to CBF transmission, as well as a reduced Cushing- like mechanism. The directional relationships between mean arterial BP (MAP ; Finometer((R)) PRO) and middle cerebral artery blood velocity (MCAv ; transcranial Doppler) were assessed at rest in 14 cervical SCI subjects and 16 uninjured individuals using Granger causality analysis, while also accounting for end-tidal CO2 tension. Those with SCI exhibited 66% increased forward MAPMCAv information transmission as compared with the uninjured group (p=0.0003), indicating reduced cerebrovascular buffering of BP, and did not have a predominant backward Cushing-like MCAvMAP phenotype. These results indicate that both forward and backward communication between BP and CBF are influenced by SCI, which may be associated with impaired cerebrovascular BP buffering after SCI as well as widespread BP instability.

We examined if the diving-induced vascular changes in the peripheral and cerebral circulation could be prevented by oral antioxidant supplementation. Fourteen divers performed a single scuba dive to eighteen meter sea water for 47 min. Twelve of the divers participated in a follow-up study involving breathing 60% of oxygen at ambient pressure for 47 min. Before both studies, participants ingested vitamin C (2 g/day) or a placebo capsule for 6 days. After a 2-wk washout, the study was repeated with the different condition. Endothelium-dependent vasodilator function of the brachial artery was assessed pre- and postintervention using the flow-mediated dilation (FMD) technique. Transcranial Doppler ultrasound was used to measure intracranial blood velocities pre- and 90 min postintervention. FMD was reduced by ∼32.8% and ∼21.2% postdive in the placebo and vitamin C trial and posthyperoxic condition in the placebo trial by ∼28.2% ( P < 0.05). This reduction in FMD was attenuated by ∼10% following vitamin C supplementation in the hyperoxic study ( P > 0.05). Elevations in intracranial blood velocities 30 min after surfacing from diving were reduced in the vitamin C study compared with the placebo trial ( P < 0.05). O2 breathing had no postintervention effects on intracranial velocities ( P > 0.05). Prophylactic ingestion of vitamin C effectively abrogated peripheral vascular dysfunction following exposure to 60% O2 but did not abolish the postdive decrease in FMD. Transient elevations of intracranial velocities postdive were reduced by vitamin C. These findings highlight the differential influence of vitamin C on peripheral and cerebral circulations following scuba diving, which are only partly mediated via hyperoxia.

The capacity of the cerebrovasculature to buffer changes in blood pressure (BP) is crucial to prevent stroke, the incidence of which is three- to fourfold elevated after spinal cord injury (SCI). Disruption of descending sympathetic pathways within the spinal cord due to cervical SCI may result in impaired cerebrovascular buffering. Only linear analyses of cerebrovascular buffering of BP, such as transfer function, have been used in SCI research. This approach does not account for inherent nonlinearity and nonstationarity components of cerebrovascular regulation, often depends on perturbations of BP to increase the statistical power, and does not account for the influence of arterial CO2 tension. Here, we used a nonlinear and nonstationary analysis approach termed wavelet decomposition analysis (WDA), which recently identified novel sympathetic influences on cerebrovascular buffering of BP occurring in the ultra-low-frequency range (ULF; 0.02–0.03Hz). WDA does not require BP perturbations and can account for influences of CO2 tension. Supine resting beat-by-beat BP (Finometer), middle cerebral artery blood velocity (transcranial Doppler), and end-tidal CO2 tension were recorded in cervical SCI ( n = 14) and uninjured ( n = 16) individuals. WDA revealed that cerebral blood flow more closely follows changes in BP in the ULF range ( P = 0.0021, Cohen’s d = 0.89), which may be interpreted as an impairment in cerebrovascular buffering of BP. This persisted after accounting for CO2. Transfer function metrics were not different in the ULF range, but phase was reduced at 0.07–0.2 Hz ( P = 0.03, Cohen’s d = 0.31). Sympathetically mediated cerebrovascular buffering of BP is impaired after SCI, and WDA is a powerful strategy for evaluating cerebrovascular buffering in clinical populations.

Molecular oxygen (O2) is a vital element in human survival and plays a major role in a diverse range of biological and physiological processes. Although normobaric hyperoxia can increase arterial oxygen content ([Formula: see text]), it also causes vasoconstriction and hence reduces O2delivery in various vascular beds, including the heart, skeletal muscle, and brain. Thus, a seemingly paradoxical situation exists in which the administration of oxygen may place tissues at increased risk of hypoxic stress. Nevertheless, with various degrees of effectiveness, and not without consequences, supplemental oxygen is used clinically in an attempt to correct tissue hypoxia (e.g., brain ischemia, traumatic brain injury, carbon monoxide poisoning, etc.) and chronic hypoxemia (e.g., severe COPD, etc.) and to help with wound healing, necrosis, or reperfusion injuries (e.g., compromised grafts). Hyperoxia has also been used liberally by athletes in a belief that it offers performance-enhancing benefits; such benefits also extend to hypoxemic patients both at rest and during rehabilitation. This review aims to provide a comprehensive overview of the effects of hyperoxia in humans from the “bench to bedside.” The first section will focus on the basic physiological principles of partial pressure of arterial O2, [Formula: see text], and barometric pressure and how these changes lead to variation in regional O2delivery. This review provides an overview of the evidence for and against the use of hyperoxia as an aid to enhance physical performance. The final section addresses pathophysiological concepts, clinical studies, and implications for therapy. The potential of O2toxicity and future research directions are also considered.

NEW FINDINGS: What is the central question of this study? How does oxygen therapy influence cerebral blood flow, cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients? What is the main finding and its importance? Oxygen therapy improves cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients. This improvement in cerebral oxygen delivery and neurovascular function might provide a physiological link between oxygen therapy and a reduced risk of cerebrovascular disease (e.g. stroke, mild cognitive impairment and dementia) in chronic obstructive pulmonary disease. ABSTRACT: We investigated the role of hypoxaemia in cerebral blood flow (CBF), oxygen delivery (CDO2 ) and neurovascular coupling (coupling of CBF to neural activity ; NVC) in hypoxaemic chronic obstructive pulmonary disease (COPD) patients (n = 14). Resting CBF (duplex ultrasound), peripheral oxyhaemoglobin saturation (SpO2 ; pulse-oximetry) and NVC (transcranial Doppler) were assessed before and after a 20 min wash-in of supplemental oxygen (∼3 l min-1 ). The peripheral oxyhaemoglobin saturation increased from 91.0 ± 3.3 to 97.4 ± 3.0% (P < 0.01), whereas CBF was unaltered (593.0 ± 162.8 versus 590.1 ± 138.5 ml min-1 ; P = 0.91) with supplemental O2 . In contrast, both CDO2 (98.1 ± 25.7 versus 108.7 ± 28.4 ml dl-1 ; P = 0.02) and NVC were improved. Specifically, the posterior cerebral artery cerebrovascular conductance was increased to a greater extent after O2 normalization (+40%, from 20.4 ± 9.9 to 28.0 ± 10.4% increase in conductance ; P = 0.04), whereas the posterior cerebral artery cerebrovascular resistance decreased to a greater extent during O2 normalization (+22%, from -16.7 ± 7.3 to -21.4 ± 6.6% decrease in resistance ; P = 0.04). The cerebral vasculature of COPD patients appears insensitive to oxygen, because CBF was unaltered in response to O2 supplementation leading to improved CDO2 . In patients, the improvements in CDO2 and neurovascular function with supplemental O2 may underlie the cognitive benefits associated with O2 therapy.

Static apnea provides a unique model that combines transient hypertension, hypercapnia, and severe hypoxemia. With apnea durations exceeding 5 min, the purpose of the present study was to determine how that affects cerebral free-radical formation and the corresponding implications for brain structure and function. Measurements were obtained before and following a maximal apnea in 14 divers with transcerebral exchange kinetics, measured as the product of global cerebral blood flow (duplex ultrasound) and radial arterial to internal jugular venous concentration differences (a-v(D)). Apnea increased the systemic (arterial) and, to a greater extent, the regional (jugular venous) concentration of the ascorbate free radical, resulting in a shift from net cerebral uptake to output (P < 0.05). Peroxidation (lipid hydroperoxides, LDL oxidation), NO bioactivity, and S100 beta were correspondingly enhanced (P < 0.05), the latter interpreted as minor and not a pathologic disruption of the blood-brain barrier. However, those changes were insufficient to cause neuronal-parenchymal damage confirmed by the lack of change in the a-v(D) of neuron-specific enolase and human myelin basic protein (P > 0.05). Collectively, these observations suggest that increased cerebral oxidative stress following prolonged apnea in trained divers may reflect a functional physiologic response, rather than a purely maladaptive phenomenon.

The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress., This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRCApnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRCApnea) hemoglobin saturation (HbSat) levels (RBRMatched) or more severe levels (RBREnd). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBRALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBRMatched was associated with reduced AP frequency and APs per burst compared with FRCApnea (both P < 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRCApnea (+10 ± 2; P < 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (HbSat: 56 ± 13 vs. 71 ± 6%; P < 0.001), RBREnd was associated with a restrained increase in the APs per burst (FRCApnea: +18 ± 7; RBREnd: +11 ± 5) and total AP clusters (FRCApnea: +10 ± 2; RBREnd: +6 ± 4) (both P < 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P < 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress. NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress.

INTRODUCTION: Many individuals with high-level spinal cord injury (SCI) experience secondary conditions such as autonomic dysreflexia (AD), which is a potentially life-threatening condition comprising transient episodes of hypertension up to 300mmHg. AD may be accompanied by symptoms and signs such as headache, flushing, and sweating. Delay in AD recognition and management is associated with increased incidence of cardiovascular events and disease. As it is commonly triggered by bladder distension, AD continues to be a major concern for individuals living with SCI, both on a daily basis and in the long-term. CASE PRESENTATION: A 58-year-old woman with C3 AIS B SCI presented with low resting blood pressure (BP) at 100/64mmHg. She reported frequent episodes of AD that were most commonly attributed to urinary bladder filling. During our testing session, her systolic BP rose to 130mmHg, at which point her care aide stepped in to utilize the Crede maneuver, which was part of her daily routine for bladder emptying. Application of suprapubic pressure further elevated her systolic BP to 230mmHg. Throughout the episode of AD, the participant experienced a pounding headache and erythema above the LOI. DISCUSSION: Clinical guidelines for bladder management after SCI recommend avoiding the Crede maneuver due to potential complications such as hernia or bruising. This current case report demonstrates the additional risk of inducing AD and dangerously high BP elevation.

What is the central question of this study? Does the reduction in cardiac output observed during extreme voluntary apnoea, secondary to high lung volume, result in a reduction in cerebral blood flow, perfusion pressure and oxygen delivery in a group of elite free divers? What is the main finding and its importance? High lung volumes reduce cardiac output and ventricular filling during extreme apnoea, but changes in cerebral blood flow are observed only transiently during the early stages of apnoea. This reveals that whilst cardiac output is important in regulating cerebral haemodynamics, the role of mean arterial pressure in restoring cerebral perfusion pressure is of greater significance to the regulation of cerebral blood flow. We investigated the role of lung volume-induced changes in cardiac output (Q̇) on cerebrovascular regulation during prolonged apnoea. Fifteen elite apnoea divers (one female; 185 ± 7 cm, 82 ± 12 kg, 29 ± 7 years old) attended the laboratory on two separate occasions and completed maximal breath-holds at total lung capacity (TLC) and functional residual capacity (FRC) to elicit disparate cardiovascular responses. Mean arterial pressure (MAP), internal jugular venous pressure and arterial blood gases were measured via cannulation. Global cerebral blood flow was quantified by ultrasound and cardiac output was quantified by via photoplethysmography. At FRC, stroke volume and Q̇ did not change from baseline (P 0.05). In contrast, during the TLC trial stroke volume and Q̇ were decreased until 80 and 40% of apnoea, respectively (P 0.05). During the TLC trial, global cerebral blood flow was significantly lower at 20%, but subsequently increased so that cerebral oxygen delivery was comparable to that during the FRC trial. Internal jugular venous pressure was significantly higher throughout the TLC trial in comparison to FRC. The MAP increased progressively in both trials but to a greater extent at TLC, resulting in a comparable cerebral perfusion pressure between trials by the end of apnoea. In summary, although lung volume has a profound effect on Q̇ during prolonged breath-holding, these changes do not translate to the cerebrovasculature owing to the greater sensitivity of cerebral blood flow to arterial blood gases and MAP; regulatory mechanisms that facilitate the maintenance of cerebral oxygen delivery.

The aims of this study were: (1) to test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with moderate-severe COPD, and (2) to test whether low flow oxygen administration improves endothelial function and is protective against oscillatory shear stress-induced endothelial dysfunction in patients with moderate-severe COPD. In 17 patients and 10 age-matched non-smoking control subjects we examined brachial artery flow-mediated dilation (FMD) and circulating microparticles before and after 20 minutes of experimentally-induced oscillatory shear stress. COPD patients performed this intervention a second time following a 20-minute wash in period of low flow supplemental oxygen to normalize arterial oxygen saturation. COPD patients had ~six-fold greater baseline retrograde shear rate (P

The cerebral metabolic rate of oxygen (CMRO2) is reduced during apnea that yields profound hypoxia and hypercapnia. In this study, to dissociate the impact of hypoxia and hypercapnia on the reduction in CMRO2, 11 breath-hold competitors completed three apneas under: (a) normal conditions (NM), yielding severe hypercapnia and hypoxemia, (b) with prior hyperventilation (HV), yielding severe hypoxemia only, and (c) with prior 100% oxygen breathing (HX), yielding the greatest level of hypercapnia, but in the absence of hypoxemia. The CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Secondary measures included net-cerebral glucose/lactate exchange and nonoxidative metabolism. Reductions in CMRO2 were largest in the HX condition (−44 ± 15%, p 2 = 58 ± 5 mmHg) but maintained oxygen saturation. The CMRO2 was reduced by 24 ± 27% in NM ( p = 0.05), but unchanged in the HV apnea where hypercapnia was absent. A net-cerebral lactate release was observed at the end of apnea in the HV and NM condition, but not in the HX apnea (main effect p 2 during apnea, and show that severe hypoxemia stimulates lactate release from the brain.

Purpose: Decompression sickness (DCS) is a poorly understood and complex systemic disease caused by inadequate desaturation following a reduction of ambient pressure. A previous proteomic study of ours showed that DCS occurrence but not diving was associated with changes in the plasma proteome in rats, including a dramatic decrease of abundance of the tetrameric form of Transthyretin (TTR). The present study aims to assess the impact on the human blood proteome of a dive inducing significant decompression stress but without inducing DCS symptoms. Experimental design: Twelve healthy male divers were subjected to a single dive at a depth of 18m of sea water (msw) with a 47-min bottom time followed by a direct ascent to the surface at a rate of 9msw/min. Venous blood was collected before the dive as well as 30mn and 2h following the dive. The plasma proteomes from four individuals were then analyzed by using a two-dimensional electrophoresis-based proteomic strategy. Results: No protein spot showed a significantly changed abundance (fdr< 0.1) between the tested times. Conclusion: These results strengthen the hypothesis according to which significant changes of the plasma proteome measurable with two-dimensional electrophoresis may only occur along with DCS symptoms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the authors' accepted and refereed manuscript to the article. Locked until 12 May 2018 due to copyright restrictions

Summary Aim SCUBA diving frequently involves repetitive exposures. The goal of this study was to see how exercise impacts microparticles (MPs), endothelial function and venous gas emboli (VGE) throughout multiple dives. Methods Sixteen divers in two groups (G1 and G2) each completed six dives, three preceded by exercise (EX) and three as controls (CON). Blood for MP analysis was collected before and after each dive. VGE were monitored via transthoracic echocardiography 30, 60 and 90 min after surfacing. Exercise before diving consisted of 60-min running including eight, 3-min intervals at 90% VO2max. Results Exercise did not have a significant impact on VGE. There was no significant difference in MP counts between EX and CON. Both groups experienced a significant decrease in MP counts in the last three dives compared to the first three (G1 P = 0·0008, G2 P = 0001). Other indices of neutrophil/platelet interaction (dual-positive CD63/41 and CD62/41) show a significant increase (P = 0·004 and 0·0001) in G2. Conclusion Both groups experienced a significant decrease in MPs at all measurements in the second series of dives compared to the first, regardless of the placement of exercise. Whether this is related to an effect of suppression of MPs or exercise timing is not clear.

Bailey, Damian M., Christopher K. Willie, Ryan L. Hoiland, Anthony R. Bain, David B. MacLeod, Maria A. Santoro, Daniel K. DeMasi, Andrea Andrijanic, Tanja Mijacika, Otto F. Barak, Zeljko Dujic, and Philip N. Ainslie. Surviving without oxygen: how low can the human brain go? High Alt Med Biol 18:73–79, 2017.—Hypoxic cerebral vasodilation is a highly conserved physiological response coupling cerebral O2 delivery (CDO2) to metabolic demand with increasingly important roles identified for the red blood cell (sensor) and nitric oxide (effector). In the current article, we reexamine previously published cerebral blood flow (CBF) and arterial blood gas data obtained in freedivers and mountaineers, extreme athletes in whom the lowest arterial partial pressures of O2 (19–23 mmHg) and greatest extremes of carbon dioxide (16–61 mmHg) were recorded during (acute) maximal static dry apnea or (chronic) exposure to terrestrial high altitude. Data highlight compensatory increases in CBF (+96% in freedivers to +2...

Purpose Trained breath-hold divers hyperinflate their lungs by glossopharyngeal insufflation (GPI) to prolong submersion time and withstand lung collapse at depths. Pulmonary hyperinflation leads to profound hemodynamic changes. Methods Thirteen divers performed preparatory breath- holds followed by apnea with GPI. Filling of extrathoracic veins was determined by ultrasound and magnetic resonance imaging and peripheral extravasation of fluid was assessed by electrical impedance. Femoral vein diameter was measured by ultrasound throughout the easy- going and struggle phase of apnea with GPI in eight divers in a sub-study. Results After GPI, pulmonary volume increased by 0.8 ± 0.6 L above total lung capacity. The diameter of the superior caval (by 36 ± 17%) and intrathoracic part of the inferior caval vein decreased (by 21 ± 16%), while the diameters of the internal jugular (by 53 ± 34%), hepatic (by 28 ± 40%), abdominal part of the inferior caval (by 28 ± 28%), and femoral veins (by 65 ± 50%) all increased (P < 0.05). Blood volume of the internal jugular, the hepatic, the abdominal part of the inferior caval vein, and the combined common iliac and femoral veins increased by 145 ± 115, 80 ± 88, 61 ± 60, and 183 ± 197%, respectively. In the sub-study, femoral vein diameter increased by 44 ± 33% in the easy-going phase of apnea with GPI, subsequently decreasing by 20 ± 16% during the struggle phase. Electrical impedance remained unchanged over the thigh and forearm, thus excluding peripheral fluid extravasation. Conclusions GPI leads to heart and pulmonary vessel compression, resulting in redistribution of blood to extrathoracic capacitance veins proximal to venous valves. This is partially reversed by the onset of involuntary breathing movements.

The effect that a SCUBA dive has on cerebral blood flow (CBF) at rest and during exercise is poorly understood. We examined the hypothesis that the altered hemodynamic parameters following a SCUBA dive will lead to differential changes in CBF at rest and during exercise. 16 divers completed a field-based study with a single dive at a depth of 18 m sea water with a 47-min bottom time. A follow-up laboratory based study was conducted - 1 week later. Intra-cranial velocities were measured with transcranial Doppler ultrasound (TCD) pre- dive, post-dive at rest and throughout incremental exercise until exhaustion. Following the dive at rest, middle cerebral artery velocity (MCAv) was elevated 15 and 30 min after surfacing (by 3.3±5.8 and 4.0±6.9 cm/s, respectively ; p

We hypothesized that the cardioselective β1-adrenoreceptor antagonist esmolol would improve maximal apnea duration in elite breath-hold divers. In elite national-level divers ( n = 9), maximal apneas were performed in a randomized and counterbalanced order while receiving either iv esmolol (150 μg·kg−1·min−1) or volume-matched saline (placebo). During apnea, heart rate (ECG), beat-by-beat blood pressure, stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were measured (finger photoplethysmography). Myocardial oxygen consumption (MV̇o2) was estimated from rate pressure product. Cerebral blood flow through the internal carotid (ICA) and vertebral arteries (VA) was assessed using Duplex ultrasound. Apnea duration improved in the esmolol trial when compared with placebo (356 ± 57 vs. 323 ± 61 s, P < 0.01) despite similar end-apnea peripheral oxyhemoglobin saturation (71.8 ± 10.3 vs. 74.9 ± 9.5%, P = 0.10). The HR response to apnea was reduced by esmolol at 10–30% of apnea duration, whereas MAP was unaffected. Esmolol reduced SV (main effect, P < 0.05) and CO (main effect; P < 0.05) and increased TPR (main effect, P < 0.05) throughout apnea. Esmolol also reduced MV̇o2 throughout apnea (main effect, P < 0.05). Cerebral blood flow through the ICA and VA was unchanged by esmolol at baseline and the last 30 s of apnea; however, global cerebral blood flow was reduced in the esmolol trial at end-apnea ( P < 0.05). Our findings demonstrate that, in elite breath-hold divers, apnea breakpoint is improved by β1-blockade, likely owing to an improved total body oxygen sparring through increased centralization of blood volume (↑TPR) and reduced MV̇o2. NEW & NOTEWORTHY The governing bodies for international apnea competition, the Association Internationale pour le Développment de l’Apnée and La Confédération Mondaile des Activités Subaquatiques, have banned the use of β-blockers based on anecdotal reports that they improve apnea duration. Using a randomized placebo-controlled trial, we are the first to empirically confirm that β-blockade improves apnea duration. This improvement in apnea duration coincided with a reduced myocardial oxygen consumption.

Pulmonary hyperinflation is used by competitive breath-hold divers and is accomplished by glossopharyngeal insufflation (GPI), which is known to compress the heart and pulmonary vessels, increasing sympathetic activity and lowering cardiac output (CO) without known consequence for organ perfusion. Myocardial, pulmonary, skeletal muscle, kidney, and liver perfusion were evaluated by magnetic resonance imaging in 10 elite breath-hold divers at rest and during moderate GPI. Cardiac chamber volumes, stroke volume, and thus CO were determined from cardiac short-axis cine images. Organ volumes were assessed from gradient echo sequences, and organ perfusion was evaluated from first-pass images after gadolinium injection. During GPI, lung volume increased by 5.2 ± 1.5 liters (mean ± SD; P < 0.001), while spleen and liver volume decreased by 46 ± 39 and 210 ± 160 ml, respectively ( P < 0.05), and inferior caval vein diameter by 4 ± 3 mm ( P < 0.05). Heart rate tended to increase (67 ± 10 to 86 ± 20 beats/min; P = 0.052) as right and left ventricular volumes were reduced ( P < 0.05). Stroke volume (107 ± 21 to 53 ± 15 ml) and CO (7.2 ± 1.6 to 4.2 ± 0.8 l/min) decreased as assessed after 1 min of GPI ( P < 0.01). Left ventricular myocardial perfusion maximum upslope and its perfusion index decreased by 1.52 ± 0.15 s−1 ( P < 0.001) and 0.02 ± 0.01 s−1 ( P < 0.05), respectively, without transmural differences. Pulmonary tissue, spleen, kidney, and pectoral-muscle perfusion also decreased ( P < 0.05), and yet liver perfusion was maintained. Thus, during pulmonary hyperinflation by GPI, CO and organ perfusion, including the myocardium, as well as perfusion of skeletal muscles, are reduced, and yet perfusion of the liver is maintained. Liver perfusion seems to be prioritized when CO decreases during GPI.

The effects of different recovery protocols on heart rate recovery (HRR) trend through fitted heart rate (HR) decay curves were assessed. Twenty one trained male athletes and 19 sedentary male students performed a submaximal cycle exercise test on four occasions followed by 5 min: 1) inactive recovery in the upright seated position, 2) active (cycling) recovery in the upright seated position, 3) supine position, and 4) supine position with elevated legs. The HRR was assessed as the difference between the peak exercise HR and the HR recorded following 60 seconds of recovery (HRR60). Additionally the time constant decay was obtained by fitting the 5 minute post-exercise HRR into a first-order exponential curve. Within- subject differences of HRR60 for all recovery protocols in both groups were significant (p < 0. 001) except for the two supine positions (p > 0.05). Values of HRR60 were larger in the group of athletes for all conditions (p < 0.001). The time constant of HR decay showed within-subject differences for all recovery conditions in both groups (p < 0.01) except for the two supine positions (p > 0.05). Between group difference was found for active recovery in the seated position and the supine position with elevated legs (p < 0.05). We conclude that the supine position with or without elevated legs accelerated HRR compared with the two seated positions. Active recovery in the seated upright position was associated with slower HRR compared with inactive recovery in the same position. The HRR in athletes was accelerated in the supine position with elevated legs and with active recovery in the seated position compared with non-athletes

The purpose of this study was to assess the effect of three different body positions on HRV measures following short-term submaximal exercise. Thirty young healthy males performed submaximal cycling for five minutes on three different occasions. Measures of HRV were obtained from 5-min R to R wave intervals before the exercise (baseline) and during the last five minutes of a 15 min recovery (post-exercise) in three different body positions (seated, supine, supine with elevated legs). Measures of the mean RR normal-to-normal intervals (RRNN), the standard deviation of normal-to-normal intervals (SDNN), the root mean square of successive differences (RMSSD) and the low-frequency (LF) and the high-frequency (HF) spectral power were analyzed. Post-exercise RRNN, RMSSD were significantly higher in the two supine positions (p < 0. 01) compared with seated body position. Post-exercise ln LF was significantly lower in the supine position with elevated legs than in the seated body position (p < 0.05). No significant difference was found among the three different body positions for post-exercise ln HF (p > 0.05). Post-exercise time domain measures of HRV (RRNN, SDNN, RMSSD) were significantly lower compared with baseline values (p < 0.01) regardless body position. Post-exercise ln LF and ln HF in all three positions remained significantly reduced during recovery compared to baseline values (p < 0.01). The present study suggests that 15 minutes following short-term submaximal exercise most of the time and frequency domain HRV measures have not returned to pre-exercise values. Modifications in autonomic cardiac regulation induced by body posture present at rest remained after exercise, but the post-exercise differences among the three positions did not resemble the ones established at rest

The 30-s all-out Wingate test has been used in athletes of all sport specialties to measure the capacity for short duration, high power output while cycling. The aim of this study was to establish differences in measuring anaerobic capacity between the classic Wingate test on a cycling ergometer and the modified Wingate test on a rowing ergometer in rowers. A group of 20 rowers was tested by both the cycle and rowing ergometers during 30s of maximum power to test anaerobic capacity and to make correlation between these tests. The parameters measured were the peak power and mean power. The peak power on the cycling ergometer was 475?75.1W and 522.4?81W (p

Muscle cell adaptation to physical activity is well known. Hypertrophy is one of the basic changes but metabolic changes are following the anatomic ones as well. The aim of the study was to follow up the changes of the ergometric parameters and surface area of the thigh muscles evoked by the heavy resistance strength training. The study included 15 male subjects, who took part in the heavy resistance strength training lasting 8 weeks. Anthropometric (surface area of the thigh muscles) and ergometric (peak power) parameters were measured at the beginning and at the end of the 8 week period in order to evaluate the changes in the thigh muscles. The surface area of the thigh muscles increased significantly (p

INTRODUCTION Wingate anaerobic test is an all-out test, which gives information about maximal anaerobic power. The aim of the study was to show characteristics of standard and modified versions of Wingate anaerobic test (WAnT), and to determine and explain the differences in observed parameters due to the measurement protocol applied. MATHERIAL AND METHODS The testing was conducted on 30 male non sportsmen, who performed usual everyday activities. The following parameters were measured: peak power or anaerobic power, mean power as a mean value of power during the whole test and explosive power or acceleration. Modified versions were performed with 5 s or 10 s delay of maximal cycling activity, during which the person was slowly pedaling. RESULTS The average values of parameters Peak power and Explosive power in our participants were 622.20?134.57 W and 89.26 ?28.57 W/s, respectively. In modification 1 Peak Power and Explosive Power were 680.25?133.43 W and 100.60?12.77 W/s, and in modification 2 they were 685.95?135.68 W and 100.30?10.09 W/s. Significant differences were found in both parameters between the standard and modified versions, but there was no significant difference between two modified versions. The mean power parameter was not considered in the discussion, because of the fact that modified versions were shortened, and it was not a valid measurement for this parameter. DISCUSION AND CONCLUSION The difference between standard and modified versions can be explained by the difference between test and retest probes, and also because of modification of protocol which can partially influence the results of testing.

Physiological mechanisms of muscle activity during cyclic physical exercises of various intensity, including individual maximum exercise intensity, have been studied in 30 athletes. The system quantization of behavior showed that the spectral components of heart rate variability during attainment of individual maximum exercise intensity by athletes change in different directions. An increase in the individual maximum exercise intensity is accompanied by an increase in the maximum movement pace after each system quantum of muscle activity and is performed at a lower heart rate. This increases the absolute spectral power of the EEG β2 range, and each system quantum of physical activity induces adequate triggering of autonomic mechanisms ensuring the activity. The results of this study may be used for professional selection or development of criteria of the endurance of athletes with regard to high cyclic exercise intensities.

Introduction. A number of articles on physical activity analyze the effects of acute bouts of physical exercise on the whole body. These experiments mainly include questionnaires and measurements of reaction time. The use of event-related potentials in laboratories for functional diagnostics is only of recent date. The aim of this experiment was to give insights into the impact of physical activity of different intensity on the amplitude and latency of P300 cognitive potentials. Material and methods. After recording cognitive event-related potentials in 17 young (21.6?1.07 yrs) healthy adults (at Fz and Cz), the participants underwent a controlled bicycle ergometer exercise. Each exercise lasted 10 minutes, with successive increase in the intensity to 60%, 75% and 90% of the maximum pulse rate and maintaining this level of intensity for six minutes. Immediately after each bout of exercise, event-related potentials were recorded. Results. The amplitude of the P300 wave, following exercise intensity at 75% of the maximum pulse (Pmax) (Fz 15.00?4.57; Cz 18.63?8.83 mV) was statistically higher (p0.05) between amplitudes at 60% of Pmax and values obtained at rest and at 90% of Pmax. Also, no statistically significant differences were recorded (p>0.05) among the latencies of P300 recorded at rest (Fz 323.57?13.24 ms; Cz 323.57?13.24 ms) and at 60% of Pmax (Fz 321.14?22.38 ms; Cz 321.86?22.88 ms), at 75% of Pmax (Fz 321.50?16.67 ms; Cz 322.50?14.60 ms) and at 90% of Pmax (Fz 326.29?7.85 ms; Cz 325.43?7.63 ms). Discusssion and Conclusion. Physical activity has a positive impact on cognitive functions. At intermediate intensities, the amplitude of P300 increases, but at submaximal intensities it decreases to values obtained at rest. However, the latency of P300 did not show a statistically significant change after different intensities of exercise.

PURPOSE: The aim of the study was to assess changes in subarachnoid space width (sas-TQ), the marker of intracranial pressure (ICP), pial artery pulsation (cc-TQ) and cardiac contribution to blood pressure (BP), cerebral blood flow velocity (CBFV) and cc-TQ oscillations throughout the maximal breath hold in elite apnoea divers. Non-invasive assessment of sas- TQ and cc-TQ became possible due to recently developed method based on infrared radiation, called near-infrared transillumination/backscattering sounding (NIR- T/BSS). METHODS: The experimental group consisted of seven breath-hold divers (six men). During testing, each participant performed a single maximal end-inspiratory breath hold. Apnoea consisted of the easy-going and struggle phases (characterised by involuntary breathing movements (IBMs)). Heart rate (HR) was determined using a standard ECG. BP was assessed using the photoplethysmography method. SaO2 was monitored continuously with pulse oximetry. A pneumatic chest belt was used to register thoracic and abdominal movements. Cerebral blood flow velocity (CBFV) was estimated by a 2-MHz transcranial Doppler ultrasonic probe. sas-TQ and cc-TQ were measured using NIR-T/BSS. Wavelet transform analysis was performed to assess cardiac contribution to BP, CBFV and cc-TQ oscillations. RESULTS: Mean BP and CBFV increased compared to baseline at the end of the easy phase and were further augmented by IBMs. cc-TQ increased compared to baseline at the end of the easy phase and remained stable during the IBMs. HR did not change significantly throughout the apnoea, although a trend toward a decrease during the easy phase and recovery during the IBMs was visible. Amplitudes of BP, CBFV and cc-TQ were augmented. sas-TQ and SaO2 decreased at the easy phase of apnoea and further decreased during the IBMs. CONCLUSIONS: Apnoea increases intracranial pressure and pial artery pulsation. Pial artery pulsation seems to be stabilised by the IBMs. Cardiac contribution to BP, CBFV and cc-TQ oscillations does not change throughout the apnoea.