Sympathetic neural activation: An ordered affair

Is there an ordered pattern in the recruitment of postganglionic sympathetic neurones? Using new multi-unit action potential detection and analysis techniques we sought to determine whether the activation of sympathetic vasomotor neurones during stress is governed by the size principle of recruitment. Multi-unit postganglionic sympathetic activity (fibular nerve) was collected from five male subjects at rest and during periods of elevated sympathetic stress (end-inspiratory apnoeas; 178 ± 37 s(mean ± S.D.)). Compared to baseline (0.24 ± 0.04 V), periods of elevated stress resulted in augmented sympathetic burst size (1.34 ± 0.38 V, P \u3c 0.05). Increased burst size was directly related to both the number of action potentials within a multi-unit burst of postganglionic sympathetic activity (r= 0.88 ± 0.04, P \u3c 0.001 in all subjects), and the amplitude of detected action potentials (r= 0.88 ± 0.06, P \u3c 0.001 in all subjects). The recruitment of larger, otherwise silent, neurons accounted for approximately 74% of the increase in detected action potentials across burst sizes. Further, action potential conduction velocities (inverse of latencies) were increased as a function of action potential size (R2= 0.936, P= 0.001). As axon diameter is positively correlated with action potential size and conduction velocity, these data suggest that the principle of ordered recruitment based on neuronal size applies to postganglionic sympathetic vasomotor neurones. This information may be pertinent to our understanding of reflex-specific recruitment strategies in postganglionic sympathetic nerves, patterns of vasomotor control during stress, and the malleability of sympathetic neuronal properties and recruitment in health and disease.The sympathetic nervous system is an important controller of blood pressure and blood flow to critical tissues and organs. In other neural systems (e.g. the skeletal motor system) there is a well understood pattern of neural recruitment during activation. Alternatively, our understanding of how sympathetic neurones are coordinated during stress is limited. We demonstrate that during stress otherwise silent sympathetic neurones are activated in an order based on neuronal size (from smallest to largest). This recruitment pattern is similar to what is known in other neural systems. This information has important implications for how blood pressure and blood flow are controlled, and the malleability of sympathetic activation in health and disease. © 2010 The Authors. Journal compilation © 2010 The Physiological Society

Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress

© 2017 the American Physiological Society. 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 \u3c 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (Hb-Sat: 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 \u3c 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P \u3c 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

Role of Cerebral Blood Flow in Extreme Breath Holding

The role of cerebral blood flow (CBF) on a maximal breath-hold (BH) in ultra-elite divers was examined. Divers (n = 7) performed one control BH, and one BH following oral administration of the non-selective cyclooxygenase inhibitor indomethacin (1.2 mg/kg). Arterial blood gases and CBF were measured prior to (baseline), and at BH termination. Compared to control, indomethacin reduced baseline CBF and cerebral delivery of oxygen (CDO(2)) by about 26% (p < 0.01). Indomethacin reduced maximal BH time from 339 ± 51 to 319 ± 57 seconds (p = 0.04). In both conditions, the CDO(2) remained unchanged from baseline to the termination of apnea. At BH termination, arterial oxygen tension was higher following oral administration of indomethacin compared to control (4.05 ± 0.45 vs. 3.44 ± 0.32 kPa). The absolute increase in CBF from baseline to the termination of apnea was lower with indomethacin (p = 0.01). These findings indicate that the impact of CBF on maximal BH time is likely attributable to its influence on cerebral H(+) washout, and therefore central chemoreceptive drive to breathe, rather than to CDO(2)

Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies

A prospective observational study (ClinicalTrial ID: NCT05771415) was conducted to compare placental oxygenation in low-risk, uncomplicated term pregnancies measured by near-infrared spectroscopy (NIRS) in relation to the placental maturity grade determined by ultrasound assessment according to the Grannum scale. We included 34 pregnancies divided into two groups according to placental maturation. For each pregnancy, measurements were taken at the site above the central part of the placenta (test) and at the site outside of the placenta on the lower abdomen (control). Student's t-test was used to compare tissue oxygenation index (TOI) values among the study groups. The normality of distribution was proven by the Kolmogorov-Smirnov test. In women with low placental maturity grade, the mean TOI value above the placenta was 70.38 +/- 3.72, which was lower than the respective value in women with high placental maturity grade (77.99 +/- 3.71; p &lt; 0.001). The TOI values above the placenta and the control site were significantly different in both groups (70.38 +/- 3.72 vs 67.83 +/- 3.21 and 77.99 +/- 3.71 vs 69.41 +/- 3.93; p &lt; 0.001). The results offer a new perspective on placental function based on specific non-invasive real-time oxygenation measurements. Unfortunately, and because of technical limitations, NIRS cannot yet be implemented as a routine clinical tool

Severe hypoxaemic hypercapnia compounds cerebral oxidative–nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function

We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015–0.044). This was associated with a general net cerebral output (v &gt; a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a &gt; v) and global cerebral blood flow (P = 0.034 to &lt;0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative–nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative–nitrosative stress

Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: implications for cerebral bioenergetic function

We examined to what extent apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox-regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (6 men, 4 women) performed two maximal dry apnoeas preceded by, [1] normoxic normoventilation resulting in severe end-apnoea hypoxaemic hypercapnia and [2] hyperoxic hyperventilation designed to ablate hypoxaemia resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (A·-, electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (NO, tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P = &lt;0.001). Apnoea generally increased gCBF (all P = &lt;0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015 to 0.044). This was associated with a general net cerebral output (v&gt;a) of A·- that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite (〖"NO" 〗_"2" ^"-" ) uptake (a&gt;v) and gCBF (P = 0.034 to &lt;0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of NO consistent with elevated cerebral oxidative-nitrosative stress (OXNOS). In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P = &gt;0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral OXNOS

Sports-related lung injury during breath-hold diving

The number of people practising recreational breath-hold diving is constantly growing, thereby increasing the need for knowledge of the acute and chronic effects such a sport could have on the health of participants. Breath-hold diving is potentially dangerous, mainly because of associated extreme environmental factors such as increased hydrostatic pressure, hypoxia, hypercapnia, hypothermia and strenuous exercise. In this article we focus on the effects of breath-hold diving on pulmonary function. Respiratory symptoms have been reported in almost 25% of breath-hold divers after repetitive diving sessions. Acutely, repetitive breath-hold diving may result in increased transpulmonary capillary pressure, leading to noncardiogenic oedema and/or alveolar haemorrhage. Furthermore, during a breath-hold dive, the chest and lungs are compressed by the increasing pressure of water. Rapid changes in lung air volume during descent or ascent can result in a lung injury known as pulmonary barotrauma. Factors that may influence individual susceptibility to breath-hold diving-induced lung injury range from underlying pulmonary or cardiac dysfunction to genetic predisposition. According to the available data, breath-holding does not result in chronic lung injury. However, studies of large populations of breath-hold divers are necessary to firmly exclude long-term lung damage

Chronic Effects of Effective Oral Cannabidiol Delivery on 24-h Ambulatory Blood Pressure and Vascular Outcomes in Treated and Untreated Hypertension (HYPER-H21-4): Study Protocol for a Randomized, Placebo-Controlled, and Crossover Study

Accumulating data from both human and animal studies suggest that cannabidiol (CBD) may be associated with improved cardiovascular function, markedly with regard to reduction in blood pressure and improved endothelial function. However, there is a lack of randomized studies to support these notions, especially in at-risk populations. The principal aim of this randomized, placebo-controlled, and crossover study is to examine the influence of chronic CBD administration on 24-h blood pressure in individuals with mild or moderate hypertension who are either untreated or receiving standard care therapy. The secondary aims of the study are to determine the safety and tolerability of 5 weeks of CBD administration, and to quantify the effect on arterial stiffness, CBD and vascular health biomarkers, inflammation, heart rate variability, and psychological well-being in both groups of patients. The present single-center study is designed as a triple blind (Participant, Investigator, Outcomes Assessor), placebo-controlled, crossover pilot study in which 70 hypertensive volunteers (aged 40&ndash;70 years) will receive DehydraTECH2.0 CBD formulation and placebo in a crossover manner. We believe that comprehensive analyses that will be performed in the present trial will decipher whether CBD is in fact a safe and valuable supplement for patients with treated and untreated hypertension

Immune and inflammatory responses to freediving calculated from leukocyte gene expression profiles

Freedivers hold their breath while diving, causing blood oxygen levels to decrease (hypoxia) while carbon dioxide increases (hypercapnia). Whereas blood gas changes are presumably involved in the progression of respiratory diseases, less is known about their effect on healthy individuals. Here we have used gene expression profiling to analyze elite athletes’ immune and inflammatory responses to freediving. Blood was collected before, 1 and 3 h after a series of maximal dynamic and static apneas in a pool, and peripheral blood gene expression was mapped on genome-wide microarrays. Fractions of phenotypically distinct immune cells were computed by deconvolution of the gene expression data using Cibersort software. Changes in gene activity and associated biological pathways were determined using R and GeneGo software. The results indicated a temporary increase of neutrophil granulocytes, and a decrease of cytotoxic lymphocytes; CD8+ T cells and resting NK cells. Biological pathway associations indicated possible protective reactions: genes involved in anti-inflammatory responses to proresolving lipid mediators were upregulated, whereas central factors involved in granule-mediated lymphocyte cytotoxicity were downregulated. While it remains unresolved whether freediving alters the immune system’s defensive function, these results provide new insight into leukocyte responses and the protection of homeostasis in healthy athletes