Device-guided slow breathing alters postprandial oxidative stress in young adult males: A randomized sham-controlled crossover trial.

BACKGROUND AND AIMS: Slow, deep breathing (SDB) lowers blood pressure (BP) though the underlying mechanisms are unknown. Redox improvements could facilitate hemodynamic adjustments with SDB though this has not been investigated. The purpose of this randomized, sham-controlled trial was to examine the acute effects of SDB on oxidative stress and endothelial function during a physiological perturbation (high-fat meal) known to induce oxidative stress. METHODS AND RESULTS: Seventeen males (ages 18-35 years) were enrolled, and anthropometric measurements and 7-day physical activity monitoring were completed. Testing sessions consisted of 24-h diet recalls (ASA24), blood sample collection for superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS) analysis, and flow-mediated dilation (FMD). High-fat meals were ingested and 2-min breathing exercises (SDB or sham control breathing) were completed every 15 min during the 4-h postprandial phase. Blood sample collection and FMD were repeated 1-, 2-, and 4-h post meal consumption. Mean body mass index and step counts were 25.6 ± 4.3 kg/m2 and 8165 ± 4405 steps per day, respectively. Systolic and diastolic BP and nutrient intake 24 h prior were similar between conditions. No time or time by condition interaction effects were observed for FMD. The total area under the curve (AUC) for SOD was significantly lower during SDB compared to the sham breathing condition (p < 0.01). No differences were observed in TBARS AUC (p = 0.538). CONCLUSIONS: Findings from the current investigation suggest that SDB alters postprandial redox in the absence of changes in endothelial function in young, healthy males. CLINICAL TRIAL REGISTRATION NUMBER: NCT04864184. CLINICAL TRIALS IDENTIFIER: NCT04864184.

Laparoscopy in children and its impact on brain oxygenation during routine inguinal hernia repair.

BACKGROUND: The systemic impact of intra-abdominal pressure (IAP) and/or changes in carbon dioxide (CO2) during laparoscopy are not yet well defined. Changes in brain oxygenation have been reported as a possible cause of cerebral hypotension and perfusion. The side effects of anaesthesia could also be involved in these changes, especially in children. To date, no data have been reported on brain oxygenation during routine laparoscopy in paediatric patients. PATIENTS AND METHODS: Brain and peripheral oxygenation were investigated in 10 children (8 male, 2 female) who underwent elective minimally invasive surgery for inguinal hernia repair. Intraoperative transcranial near-infrared spectroscopy to assess regional cerebral oxygen saturation (rScO2), peripheral oxygen saturation using pulse oximetry and heart rate (HR) were monitored at five surgical intervals: Induction of anaesthesia (baseline T1); before CO2insufflation induced pneumoperitoneum (PP) (T2); CO2PP insufflation (T3); cessation of CO2PP (T4); before extubation (T5). RESULTS: rScO2decreases were recorded immediately after T1 and became significant after insufflation (P = 0.006; rScO2decreased 3.6 ± 0.38%); restoration of rScO2was achieved after PP cessation (P = 0.007). The changes in rScO2were primarily due to IAP increases (P = 0.06). The HR changes were correlated to PP pressure (P < 0.001) and CO2flow rate (P = 0.001). No significant peripheral effects were noted. CONCLUSIONS: The increase in IAP is a critical determinant in cerebral oxygenation stability during laparoscopic procedures. However, the impact of anaesthesia on adaptive changes should not be underestimated. Close monitoring and close collaboration between the members of the multidisciplinary paediatric team are essential to guarantee the patient's safety during minimally invasive surgical procedures.

Integrated Cardio-Respiratory Control: Insight in Diabetes.

Autonomic dysfunction is a frequent and relevant complication of diabetes mellitus, as it is associated with increased morbidity and mortality. In addition, it is today considered as predictive of the most severe diabetic complications, like nephropathy and retinopathy. The classical methods of screening are the cardiovascular reflex tests and were originally interpreted as evidence of nerve damage. A more modern approach, based on the integrated control of cardiovascular and respiratory function, reveals that these abnormalities are to a great extent functional, at least in the early stage of the disease, thus suggesting new potential interventions. Therefore, this review aims to go further investigating how the imbalance of the autonomic nervous system is altered and can be influenced in many chronic pathologies through a global view of cardio-respiratory and metabolic interactions and how the same mechanisms are applicable to diabetes.

Diagnostic role of head-up tilt test in patients with cough syncope.

AIMS: The aim of this study was to describe the head-up tilt (HUT) test and carotid sinus massage (CSM) responses, and the occurrence of syncope with coughing during HUT in a large cohort of patients. METHODS AND RESULTS: A total of 5133 HUT were retrospectively analysed to identify patients with cough syncope. Head-up tilt followed by CSM were performed. Patients were made to cough on two separate occasions in an attempt to reproduce typical clinical symptoms on HUT. Patients with cough syncope were compared with 29 age-matched control patients with syncope unrelated to coughing. A total of 29 patients (26 male, age 49 ± 14 years) with cough syncope were identified. Coughing during HUT reproduced typical prodromal symptoms of syncope in 16 (55%) patients and complete loss of consciousness in 2 (7%) patients, with a mean systolic blood pressure reduction of 45 ± 26 mmHg, and a mean increase in heart rate of 13 ± 8 b.p.m. No syncope or symptoms after coughing were observed in the control group. The HUT result was positive in 13 (48%) patients with the majority of positive HUT responses being vasodepressor (70% of positive HUT). Carotid sinus massage was performed in 18 patients being positive with a vasodepressor response causing mild pre-syncopal symptoms in only 1 patient. CONCLUSION: Syncope during coughing is a result of hypotension, rather than bradycardia. Coughing during HUT is a useful test in patients suspected to have cough syncope but in whom the history is not conclusive.

The association between blood oxygen saturation and baroreflex sensitivity in adults with type 1 diabetes with and without albuminuria.

BACKGROUND: Low baroreflex sensitivity is an indicator of early cardiovascular autonomic neuropathy. We explored the association between baroreflex sensivity and blood oxygen saturation (SpO2) in type 1 diabetes and various degrees of microvascular disease. METHODS: In this Danish-Finnish cross-sectional multicentre study, baroreflex sensivity and SpO2 (pulse oximetry) were examined in persons with type 1 diabetes and normoalbuminuria (n = 98), microalbuminuria (n = 28), or macroalbuminuria (n = 43), and in non-diabetic controls (n = 54). Associations and differences between groups were analysed using regression models and adjustment included age, sex, smoking, HbA1c, blood haemoglobin, urine albumin creatinine ratio, body mass index, and estimated glomerular filtration rate. RESULTS: In type 1 diabetes, higher baroreflex sensitivity was associated with higher SpO2 before adjustment (% increase per one % increase in SpO2 = 20 % (95%CI: 11-30); p < 0.001) and the association remained significant after adjustment (p = 0.02). Baroreflex sensitivity was not different between non-diabetic controls and persons with type 1 diabetes and normoalbuminuria (p = 0.052). Compared with type 1 diabetes and normoalbuminuria, baroreflex sensitivity was lower in micro- (p < 0.001) and macroalbuminuria (p < 0.001). SpO2 was lower in persons with type 1 diabetes and normoalbuminuria compared with non-diabetic controls (p < 0.01). Within the participants with type 1 diabetes, SpO2 was not different in micro- or macroalbuminuria compared with normoalbuminuria (p-values > 0.05), but lower in macro-compared with microalbuminuria (p < 0.01). CONCLUSIONS: Lower baroreflex sensitivity was associated with lower SpO2 in type 1 diabetes. The present study support the hypothesis that hypoxia could be a therapeutic target in persons with type 1 diabetes.

Repression of hypoxia-inducible factor-1 contributes to increased mitochondrial reactive oxygen species production in diabetes.

Background: Excessive production of mitochondrial reactive oxygen species (ROS) is a central mechanism for the development of diabetes complications. Recently, hypoxia has been identified to play an additional pathogenic role in diabetes. In this study, we hypothesized that ROS overproduction was secondary to the impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Methods: The ROS levels were analyzed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia. The relation between HIF-1, glucose levels, ROS production and its functional consequences were analyzed in renal mIMCD-3 cells and in kidneys of mouse models of diabetes. Results: Exposure to hypoxia increased circulating ROS in subjects with diabetes, but not in subjects without diabetes. High glucose concentrations repressed HIF-1 both in hypoxic cells and in kidneys of animals with diabetes, through a HIF prolyl-hydroxylase (PHD)-dependent mechanism. The impaired HIF-1 signaling contributed to excess production of mitochondrial ROS through increased mitochondrial respiration that was mediated by Pyruvate dehydrogenase kinase 1 (PDK1). The restoration of HIF-1 function attenuated ROS overproduction despite persistent hyperglycemia, and conferred protection against apoptosis and renal injury in diabetes. Conclusions: We conclude that the repression of HIF-1 plays a central role in mitochondrial ROS overproduction in diabetes and is a potential therapeutic target for diabetic complications. These findings are timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use. Funding: This work was supported by grants from the Swedish Research Council, Stockholm County Research Council, Stockholm Regional Research Foundation, Bert von Kantzows Foundation, Swedish Society of Medicine, Kung Gustaf V:s och Drottning Victorias Frimurarestifelse, Karolinska Institute's Research Foundations, Strategic Research Programme in Diabetes, and Erling-Persson Family Foundation for S-B.C.; grants from the Swedish Research Council and Swedish Heart and Lung Foundation for T.A.S.; and ERC consolidator grant for M.M.

Methods of investigation for cardiac autonomic dysfunction in human research studies.

This consensus document provides evidence-based guidelines regarding the evaluation of diabetic cardiovascular autonomic neuropathy (CAN) for human research studies; the guidelines are the result of the work of the CAN Subcommittee of the Toronto Diabetic Neuropathy Expert Group. The subcommittee critically reviewed the limitations and strengths of the available diagnostic approaches for CAN and the need for developing new tests for autonomic function. It was concluded that the most sensitive and specific approaches currently available to evaluate CAN in clinical research are: (1) heart rate variability, (2) baroreflex sensitivity, (3) muscle sympathetic nerve activity, (4) plasma catecholamines, and (5) heart sympathetic imaging. It was also recommended that efforts should be undertaken to develop new non-invasive and safe CAN tests to be used in clinical research, with higher sensitivity and specificity, for studying the pathophysiology of CAN and evaluating new therapeutic approaches.

Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management.

The Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of the Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control in the setting of diabetes after exclusion of other causes. The prevalence of confirmed CAN is around 20%, and increases up to 65% with age and diabetes duration. Established risk factors for CAN are glycaemic control in type 1 and a combination of hypertension, dyslipidaemia, obesity, and glycaemic control in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: (1) one abnormal cardiovagal test result identifies possible or early CAN; (2) at least two abnormal cardiovagal test results are required for definite or confirmed CAN; and (3) the presence of orthostatic hypotension in addition to abnormal heart rate test results identifies severe or advanced CAN. Progressive stages of CAN are associated with increasingly worse prognosis. CAN assessment is relevant in clinical practice for (1) diagnosis of CAN clinical forms, (2) detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, orthostatic hypotension, non-dipping, QT interval prolongation), (3) risk stratification for diabetic complications and cardiovascular morbidity and mortality, and (4) modulation of targets of diabetes therapy. Evidence on the cost-effectiveness of CAN testing is lacking. Apart from the preventive role of intensive glycaemic control in type 1 diabetes, recommendations cannot be made for most therapeutic approaches to CAN.

Arterial baroreflex modulation influences postural sway.

OBJECTIVE: Although considered mainly a random function, postural sway is influenced by physiological factors such as respiration. A direct effect of the autonomic nervous system (ANS) on posture has never been demonstrated. To test this hypothesis, we used a pure motion-independent autonomic stimulus (neck suction) to modulate the carotid baroreceptors on a broad frequency range, distinct from that of respiration. METHODS: Thirteen healthy subjects (age 26 ± 5 years) were studied upright, eyes closed, and on a force platform during controlled breathing (15 breath/min, 0.25 Hz), with and without stimulation of arterial baroreceptors by sinusoidal neck suction (0 to -30 mmHg pressure) at different frequencies (0.05, 0.10, 0.125, 0.15, 0.175, 0.20, 0.30 Hz), for eight periods lasting 2 min each. The increase in sway, R-R interval and blood pressure induced at each stimulation frequency was measured by spectral analysis. RESULTS: With neck suction, we observed a significant (p < 0.05) increase in oscillations synchronous in the R-R interval (from 0.10 to 0.20 Hz), systolic and diastolic blood pressure (from 0.05 to 0.15 Hz) and sway (from 0.10 to 0.30 Hz in both the antero-posterior and medio-lateral planes). Changes were greater in the left than in the right foot. CONCLUSION: Our study shows that postural sway is modulated by the ANS and is influenced by phasic stimulation of the arterial (carotid) baroreceptors. Our findings have potentially important clinical implications in the development of treatment strategies for pathological conditions in which alterations in posture and autonomic function coexist and could be mutually influenced.

Persons with type 1 diabetes have low blood oxygen levels in the supine and standing body positions.

INTRODUCTION: Blood oxygen saturation is low compared with healthy controls (CONs) in the supine body position in individuals with type 1 diabetes (T1D) and has been associated with complications. Since most of daily life occurs in the upright position, it is of interest if this also applies in the standing body position. In addition, tissue oxygenation in other anatomical sites could show different patterns in T1D. Therefore, we investigated blood, arm and forehead oxygen levels in the supine and standing body positions in individuals with T1D (n=129) and CONs (n=55). RESEARCH DESIGN AND METHODS: Blood oxygen saturation was measured with pulse oximetry. Arm and forehead mixed tissue oxygen levels were measured with near-infrared spectroscopy sensors applied on the skin. RESULTS: Data are presented as least squares means±SEM and differences (95% CIs). Overall blood oxygen saturation was lower in T1D (CON: 97.6%±0.2%; T1D: 97.0%±0.1%; difference: -0.5% (95% CI -0.9% to -0.0%); p=0.034). In all participants, blood oxygen saturation increased after standing up (supine: 97.1%±0.1%; standing: 97.6%±0.2%; difference: +0.6% (95% CI 0.4% to 0.8%); p<0.001). However, the increase was smaller in T1D compared with CON (CON supine: 97.3%±0.2%; CON standing: 98.0%±0.2%; T1D supine: 96.9%±0.2%; T1D standing: 97.2%±0.1%; difference between groups in the change: -0.4% (95% CI -0.6% to -0.2%); p<0.001). Arm oxygen saturation decreased in both groups after standing and more in those with T1D. Forehead oxygen saturation decreased in both groups after standing and there were no differences between the changes when comparing the groups. CONCLUSION: Compared with CON, individuals with T1D exhibit possible detrimental patterns of tissue oxygen adaptation to standing, with preserved adaptation of forehead oxygenation. Further studies are needed to explore the consequences of these differences.

Dynamic interactions between musical, cardiovascular, and cerebral rhythms in humans.

BACKGROUND: Reactions to music are considered subjective, but previous studies suggested that cardiorespiratory variables increase with faster tempo independent of individual preference. We tested whether compositions characterized by variable emphasis could produce parallel instantaneous cardiovascular/respiratory responses and whether these changes mirrored music profiles. METHODS AND RESULTS: Twenty-four young healthy subjects, 12 musicians (choristers) and 12 nonmusician control subjects, listened (in random order) to music with vocal (Puccini's "Turandot") or orchestral (Beethoven's 9th Symphony adagio) progressive crescendos, more uniform emphasis (Bach cantata), 10-second period (ie, similar to Mayer waves) rhythmic phrases (Giuseppe Verdi's arias "Va pensiero" and "Libiam nei lieti calici"), or silence while heart rate, respiration, blood pressures, middle cerebral artery flow velocity, and skin vasomotion were recorded.Common responses were recognized by averaging instantaneous cardiorespiratory responses regressed against changes in music profiles and by coherence analysis during rhythmic phrases. Vocal and orchestral crescendos produced significant (P=0.05 or better) correlations between cardiovascular or respiratory signals and music profile, particularly skin vasoconstriction and blood pressures, proportional to crescendo, in contrast to uniform emphasis, which induced skin vasodilation and reduction in blood pressures. Correlations were significant both in individual and group-averaged signals. Phrases at 10-second periods by Verdi entrained the cardiovascular autonomic variables. No qualitative differences in recorded measurements were seen between musicians and nonmusicians. CONCLUSIONS: Music emphasis and rhythmic phrases are tracked consistently by physiological variables. Autonomic responses are synchronized with music, which might therefore convey emotions through autonomic arousal during crescendos or rhythmic phrases.

New method to measure and improve consistency of baroreflex sensitivity values.

OBJECTIVE: Baroreflex sensitivity (BRS) is an important prognostic index in cardiovascular diseases, however, its use is complicated by different methods difficult to compare and standardize, often providing conflicting results. We tested whether the simple ratio of RR interval to systolic blood pressure global variabilities (assessed by standard deviations) is a reliable measure of BRS, by measuring the agreement with six established methods. In addition, we tested whether high-pass filtering of data, by removing slow non-baroreflex-mediated fluctuations, could improve the agreement between different BRS methods. METHODS: In 1,409 subjects, we compared 6 established methods (derived by cross-spectral and sequence analysis) and the new method, supine and in response to tilting (1,175 subjects). Data were analyzed after linear detrending, high-pass filtering at 0.025 and 0.05 Hz. RESULTS: Although all seven methods showed a general agreement, the new method consistently showed the lowest distance from the median of the remaining methods (0.04 ± 0.06 ms/mmHg over 2,584 files, p < 0.05 with respect to the second best method). High-pass filtering improved (p < 0.001) the agreement between methods without reducing the sensitivity to changes induced by tilting. Only the new method could provide estimates in all 2,584 files tested. INTERPRETATION: The new method intercepts the mean information of all other methods better than any other method, hence providing a simple, easy to standardize (no mathematical constraints) and yet robust and reliable BRS estimate. High-pass filtering markedly improves the agreement of all methods, without loss of sensitivity, and could be routinely used in clinical trials, to provide comparable BRS estimates.

Persistence of baroreceptor control of cerebral blood flow velocity at a simulated altitude of 5000 m.

OBJECTIVE: To assess the effects of acute exposure to simulated high altitude on baroreflex control of mean cerebral blood flow velocity (MCFV). PATIENTS AND METHODS: We compared beat-to-beat changes in RR interval, arterial blood pressure, mean MCFV (by transcranial Doppler velocimetry in the middle cerebral artery), end-tidal CO2, oxygen saturation and respiration in 19 healthy subjects at baseline (Albuquerque, 1779 m), after acute exposure to simulated high altitude in a hypobaric chamber (barometric pressure as at 5000 m) and during oxygen administration (to achieve 100% oxygen saturation) at the same barometric pressure (HOX). Baroreflex control on each signal was assessed by univariate and bivariate power spectral analysis performed on time series obtained during controlled (15 breaths/min) breathing, before and during baroreflex modulation induced by 0.1-Hz sinusoidal neck suction. RESULTS: At baseline, neck suction was able to induce a clear increase in low-frequency power in MCFV (P<0.001) as well as in RR and blood pressure. At high altitude, MCFV, as well as RR and blood pressure, was still able to respond to neck suction (all P<0.001), compared to controlled breathing alone, despite marked decreases in end-tidal CO2 and oxygen saturation at high altitude. A similar response was obtained at HOX. Phase delay analysis excluded a passive transmission of low-frequency oscillations from arterial pressure to cerebral circulation. CONCLUSIONS: During acute exposure to high altitude, cerebral blood flow is still modulated by the autonomic nervous system through the baroreflex, whose sensitivity is not affected by changes in CO2 and oxygen saturation levels.

Acute fall and long-term rise in oxygen saturation in response to meditation.

The effects of meditation on arterial and tissue oxygenation are unknown and difficult to assess because respiration is often altered, directly or indirectly, during meditation practice. Thus, changes in respiration may affect cardiovascular responses independently from meditation. In this study, we aim to isolate the specific effect of meditation on arterial and tissue oxygenation and other cardiorespiratory indexes while systematically controlling for the role of respiration. Furthermore, we aim to clarify to what extent prior expertise in meditation practice is needed to observe reliable changes. Eighty participants, half with and half without prior meditation experience, were tested while pacing breathing at predetermined rates, in the presence or absence of mantra meditation instructions, and in a body scan meditation that did not involve controlled breathing. Continuous recordings were acquired for arterial and brain oxygenation, respiratory excursion, electrocardiogram, skin vasomotion, and blood pressure. In both groups, meditation acutely decreased arterial and cerebral oxygen saturation, reduced chemoreflex sensitivity, and prolonged the RR interval, independently of respiration. Conversely, slow breathing improved heart rate variability, independently of concurrent meditation. In addition to the immediate effects of meditation, the individuals with long-term practice of meditation had overall higher arterial and cerebral oxygen saturation, overall lower blood pressure, and slower baseline respiration. Meditation acutely lowers arterial and tissue oxygenation. A repeated exposure to this condition may lead to long-term adaptation and, through increased ventilatory efficiency and improved gas exchanges, to an increase in baseline oxygenation. Meditation induces favorable changes in cardiovascular and respiratory end points of clinical interest.

Increase in Synchronization of Autonomic Rhythms between Individuals When Listening to Music.

In light of theories postulating a role for music in forming emotional and social bonds, here we investigated whether endogenous rhythms synchronize between multiple individuals when listening to music. Cardiovascular and respiratory recordings were taken from multiple individuals (musically trained or music-naïve) simultaneously, at rest and during a live concert comprising music excerpts with varying degrees of complexity of the acoustic envelope. Inter-individual synchronization of cardiorespiratory rhythms showed a subtle but reliable increase during passively listening to music compared to baseline. The low-level auditory features of the music were largely responsible for creating or disrupting such synchronism, explaining ~80% of its variance, over and beyond subjective musical preferences and previous musical training. Listening to simple rhythms and melodies, which largely dominate the choice of music during rituals and mass events, brings individuals together in terms of their physiological rhythms, which could explain why music is widely used to favor social bonds.

Oxygen-induced impairment in arterial function is corrected by slow breathing in patients with type 1 diabetes.

Hyperoxia and slow breathing acutely improve autonomic function in type-1 diabetes. However, their effects on arterial function may reveal different mechanisms, perhaps potentially useful. To test the effects of oxygen and slow breathing we measured arterial function (augmentation index, pulse wave velocity), baroreflex sensitivity (BRS) and oxygen saturation (SAT), during spontaneous and slow breathing (6 breaths/min), in normoxia and hyperoxia (5 L/min oxygen) in 91 type-1 diabetic and 40 age-matched control participants. During normoxic spontaneous breathing diabetic subjects had lower BRS and SAT, and worse arterial function. Hyperoxia and slow breathing increased BRS and SAT. Hyperoxia increased blood pressure and worsened arterial function. Slow breathing improved arterial function and diastolic blood pressure. Combined administration prevented the hyperoxia-induced arterial pressure and function worsening. Control subjects showed a similar pattern, but with lesser or no statistical significance. Oxygen-driven autonomic improvement could depend on transient arterial stiffening and hypertension (well-known irritative effect of free-radicals on endothelium), inducing reflex increase in BRS. Slow breathing-induced improvement in BRS may result from improved SAT, reduced sympathetic activity and improved vascular function, and/or parasympathetic-driven antioxidant effect. Lower oxidative stress could explain blunted effects in controls. Slow breathing could be a simple beneficial intervention in diabetes.

Effect of treatment with nasal continuous positive airway pressure on ventilatory response to hypoxia and hypercapnia in patients with sleep apnea syndrome.

BACKGROUND: The increase in peripheral chemoreflex sensitivity in patients with obstructive sleep apnea (OSA) is associated with activation of autonomic nervous system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment for OSA, but little is known on its effect on chemoreflex sensitivity. OBJECTIVES: To assess the effect of nCPAP treatment or placebo (sham nCPAP) on ventilatory control in patients with OSA. SETTING: Sleep laboratory of Azienda Ospedaliera Garibaldi. PATIENTS: Twenty-five patients with moderate-to-severe OSA. DESIGN AND MEASUREMENTS: Patients were randomly assigned to either therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1 month. A rebreathing test to assess ventilatory response to normocapnic hypoxia and normoxic hypercapnia was performed at basal condition and after 1 month of treatment. RESULTS: The use of therapeutic nCPAP or sham nCPAP did not affect daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The normocapnic hypoxic ventilatory response was reduced after 1 month of treatment with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53 +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and 0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively). The normoxic hypercapnic ventilatory response remained unchanged after 1 month in both groups. No changes in ventilatory response to either hypoxia or hypercapnia were observed after a single night of nCPAP treatment. CONCLUSION: The ventilatory response to hypoxia is reduced during regular treatment, but not after short-term treatment, with nCPAP. Readjusted peripheral oxygen chemosensitivity during nCPAP treatment may be a side effect of both reduced sympathetic activity and increased baroreflex activity, or a possible continuous positive airway pressure-related mechanism leading to a reduced activation of autonomic nervous system per se.

Frequency-dependent baroreflex control of blood pressure and heart rate during physical exercise.

BACKGROUND: It is widely recognised that during exercise vagal heart rate control is markedly impaired but blood pressure control may or may not be retained. We hypothesised that this uncertainty arose from the differing responses of the vagus (fast) and sympathetic (slow) arms of the autonomic effectors, and to differing sympatho-vagal balance at different exercise intensities. METHODS AND RESULTS: We studied 12 normals at rest, during moderate (50% maximal heart rate) and submaximal (80% maximal heart rate) exercise. The carotid baroreceptors were stimulated by sinusoidal neck suction at the frequency of the spontaneous high- (during moderate exercise) and low-frequency (during submaximal) fluctuations in heart period and blood pressure. The increases in these oscillations induced by neck suction were measured by autoregressive spectral analysis. At rest neck stimulation increased variability at low frequency (RR: from 6.99+/-0.24 to 8.87+/-0.18 ln-ms2; systolic pressure: from 3.05+/-1.7 to 4.09+/-0.17 ln-mm Hg2) and high frequency (RR: from 4.67+/-0.25 to 6.79+/-0.31 ln-ms2; systolic pressure: from 1.93+/-0.2 to 2.67+/-0.125 ln-mm Hg2) (all p<0.001). During submaximal exercise RR variability decreased but systolic pressure variability rose (p<0.01 vs rest); during submaximal exercise low-frequency neck stimulation increased the low-frequency fluctuations in blood pressure (2.35+/-0.51 to 4.25+/-0.38 ln-mm Hg2, p<0.05) and RR. Conversely, neck suction at high frequency was ineffective on systolic pressure, and had only minor effects on RR interval during moderate exercise. CONCLUSION: During exercise baroreflex control is active on blood pressure, but the efferent response on blood pressure and heart rate is only detected during low frequency stimulation, indicating a frequency-dependent effect.

Seven Passive 1-h Hypoxia Exposures Do Not Prevent AMS in Susceptible Individuals.

PURPOSE: The present study evaluated the effects of a preacclimatization program comprising seven passive 1-h exposures to 4500-m normobaric hypoxia on the prevalence and severity of acute mountain sickness (AMS) during a subsequent exposure to real high altitude in persons susceptible to AMS. METHODS: The project was designed as a randomized controlled trial including 32 healthy female and male participants with known susceptibility to AMS symptoms. After baseline measurements, participants were randomly assigned to the hypoxia or the control group to receive the preacclimatization program (seven passive 1-h exposures within 7 d to normobaric hypoxia or sham hypoxia). After completing preacclimatization, participants were transported (bus, cog railway) to real high altitude (3650 m, Mönchsjoch Hut, Switzerland) and stayed there for 45 h (two nights). Symptoms of AMS and physiological responses were determined repeatedly. RESULTS: AMS incidence and severity did not significantly differ between groups during the high-altitude exposure. In total, 59% of the hypoxia and 67% of the control group suffered from AMS at one or more time points during the high-altitude exposure. Hypoxic and hypercapnic ventilatory responses were not affected by the preacclimatization program. Resting ventilation at high altitude tended to be higher (P = 0.06) in the hypoxia group compared with the control group. No significant between-group differences were detected for heart rate variability, arterial oxygen saturation, and hematological and ventilatory parameters during the high-altitude exposure. CONCLUSION: Preacclimatization using seven passive 1-h exposures to normobaric hypoxia corresponding to 4500 m did not prevent AMS development during a subsequent high-altitude exposure in AMS-susceptible persons.

Oxygen deteriorates arterial function in type 1 diabetes.

AIMS: Although oxygen is commonly used to treat various medical conditions, it has recently been shown to worsen vascular function (arterial stiffness) in healthy volunteers and even more in patients in whom vascular function might already be impaired. The effects of oxygen on arterial function in patients with type 1 diabetes (T1D) are unknown, although such patients display disturbed vascular function already at rest. Therefore, we tested whether short-term oxygen administration may alter the arterial function in patients with T1D. METHODS: We estimated arterial stiffness by augmentation index (AIx) and the pulse wave velocity equivalent (SI-DVP) in 98 patients with T1D and 49 age- and sex-matched controls at baseline and during hyperoxia by obtaining continuous noninvasive finger pressure waveforms using a recently validated method. RESULTS: AIx and SI-DVP increased in patients (P < 0.05) but not in controls in response to hyperoxia. The increase in AIx (P = 0.05), systolic (P < 0.05), and diastolic (P < 0.05) blood pressure was higher in the patients than in the controls. CONCLUSIONS: Short-term oxygen administration deteriorates arterial function in patients with T1D compared to non-diabetic control subjects. Since disturbed arterial function plays a major role in the development of diabetic complications, these findings may be of clinical relevance.