Physiological responses to hypoxic constant-load and high-intensity interval exercise sessions in healthy subjects.

PURPOSE: The aim of this study was to assess the acute cardiorespiratory as well as muscle and cerebral tissue oxygenation responses to submaximal constant-load (CL) and high-intensity interval (HII) cycling exercise performed in normoxia and in hypoxia at similar intensity, reproducing whole-body endurance exercise training sessions as performed in sedentary and clinical populations. METHODS: Healthy subjects performed two CL (30 min, 75% of maximal heart rate, n = 12) and two HII (15 times 1-min high-intensity exercise-1-min passive recovery, n = 12) cycling exercise sessions in normoxia and in hypoxia [mean arterial oxygen saturation 76 ± 1% (clamped) during CL and 77 ± 5% (inspiratory oxygen fraction 0.135) during HII]. Cardiorespiratory and near-infrared spectroscopy parameters as well as the rate of perceived exertion were continuously recorded. RESULTS: Power output was 21 ± 11% and 15% (according to protocol design) lower in hypoxia compared to normoxia during CL and HII exercise sessions, respectively. Heart rate did not differ between normoxic and hypoxic exercise sessions, while minute ventilation was higher in hypoxia during HII exercise only (+ 13 ± 29%, p < 0.05). Quadriceps tissue saturation index did not differ significantly between normoxia and hypoxia (CL 60 ± 8% versus 59 ± 5%; HII 59 ± 10% versus 56 ± 9%; p > 0.05), while prefrontal cortex deoxygenation was significantly greater in hypoxia during both CL (66 ± 4% versus 56 ± 6%) and HII (58 ± 5% versus 55 ± 5%; p < 0.05) sessions. The rate of perceived exertion did not differ between normoxic and hypoxic CL (2.4 ± 1.7 versus 2.9 ± 1.8) and HII (6.9 ± 1.4 versus 7.5 ± 0.8) sessions (p > 0.05). CONCLUSION: This study indicates that at identical heart rate, reducing arterial oxygen saturation near 75% does not accentuate muscle deoxygenation during both CL and HII exercise sessions compared to normoxia. Hence, within these conditions, larger muscle hypoxic stress should not be expected.

Cerebral homeostasis and orthostatic responses in residents of the highest city in the world.

Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. Healthy male participants living at sea-level (LL; n = 15), 3800 m (HL3800m; n = 13) and 5100 m (HL5100m; n = 17), respectively, and CMS highlanders living at 5100 m (n = 31) were recruited. Middle cerebral artery mean blood flow velocity (MCAv), cerebral oxygen delivery (CDO2), mean blood pressure (MAP), heart rate variability and spontaneuous cardiac baroreflex sensitivity (cBRS) were assessed while sitting, initial 30 s and after 3 min of standing. Cerebral autoregulation index (ARI) was estimated (ΔMCAv%baseline)/ΔMAP%baseline) in response to the orthostatic challenge. Altitude and CMS were associated with hypoxemia and elevated hemoglobin concentration. While sitting, MCAv and LFpower negatively correlated with altitude but were not affected by CMS. CDO2 remained preserved. BRS was comparable across all altitudes, but lower with CMS. Within initial 30 s of standing, altitude and CMS correlated with a lesser ΔMAP while ARI remained unaffected. After 3 min standing, MCAv, CDO2 and cBRS remained preserved across altitudes. The LF/HF ratio increased in HL5100m compared to LL and HL3800m from sitting to standing. In contrary, CMS showed blunted autonomic nervous activation in responses to standing. Despite altitude- and CMS-associated hypoxemia, erythrocytosis and impaired blood pressure regulation (CMS only), cerebral homeostasis remained overall preserved.

Early effects of acetazolamide on hemoglobin mass and plasma volume in chronic mountain sickness at 5100 m.

INTRODUCTION AND OBJECTIVES: Chronic Mountain Sickness (CMS) syndrome, combining excessive erythrocytosis and clinical symptoms in highlanders, remains a public health concern in high-altitude areas, especially in the Andes, with limited therapeutic approaches. The objectives of this study were to assess in CMS-highlanders permanently living in La Rinconada (5100-5300 m, Peru, the highest city in the world), the early efficacy of acetazolamide (ACZ) and atorvastatin to reduce hematocrit (Hct), as well as the underlying mechanisms focusing on intravascular volumes. MATERIALS AND METHODS: Forty-one males (46±8 years of age) permanently living in La Rinconada for 15 [10-20] years and suffering from CMS were randomized between ACZ (250 mg once-daily; N = 13), atorvastatin (20 mg once-daily; N = 14) or placebo (N = 14) uptake in a double-blinded parallel study. Hematocrit (primary endpoint) as well as arterial blood gasses, total hemoglobin mass (Hbmass) and intravascular volumes were assessed at baseline and after a mean (±SD) treatment duration of 19±2 days. RESULTS: ACZ increased PaO2 by +13.4% (95% CI: 4.3 to 22.5%) and decreased Hct by -5.2% (95% CI: -8.3 to -2.2%), whereas Hct remained unchanged with placebo or atorvastatin. ACZ tended to decrease Hbmass (-2.6%, 95% CI: -5.7 to 0.5%), decreased total red blood cell volume (RBCV, -5.3%, 95% CI: -10.3 to -0.3%) and increased plasma volume (PV, +17.6%, 95% CI: 4.9 to 30.3%). Atorvastatin had no effect on intravascular volumes, while Hbmass and RBCV increased in the placebo group (+6.1%, 95% CI: 4.2 to 7.9% and +7.0%, 95%CI: 2.7 to 11.4%, respectively). CONCLUSIONS: Short-term ACZ uptake was effective to reduce Hct in CMS-highlanders living at extreme altitude >5,000 m and was associated with both an increase in PV and a reduction in RBCV.

[Adaptation to altitude in respiratory diseases]. / Adaptation à l'altitude dans les maladies respiratoires.

The frequency of high-altitude sojourns (for work, leisure, air travel or during car/train journeys) justifies the question of their tolerance, especially in people with pre-existing respiratory disease. Reduced barometric pressure and abrupt variations in temperature and inhaled air density may be responsible for modifications affecting the respiratory system and, in fine, oxygenation. These modifications may compromise altitude tolerance, further worsen respiratory dysfunction and render physical exercise more difficult. In obstructive lung disease, altitude is associated with gas exchange impairment, increased ventilation at rest and during exercise and heightened pulmonary artery pressure through hypoxic vasoconstriction, all of which may worsen dyspnea and increase the risk of altitude intolerance (acute mountain sickness, AMS). The most severe patients require rigorous evaluation, and hypoxic testing can be proposed. People with mild to moderate intermittent asthma can plan high altitude sojourns, provided that they remain under control at night and during exercise, and follow an adequate action plan in case of exacerbation. Respiratory disease patients with pulmonary artery hypertension (PAH) and chemoreflex control abnormalities need to be identified as at risk of altitude intolerance.

[Physiological and pathological responses to altitude]. / Réponses physiologiques et pathologiques à l'altitude.

Hypobaric hypoxia, the hallmark of a high altitude environment, has important physiological effects on both the cardiovascular and respiratory systems in order to maintain a balance between oxygen demand and supply. This dynamic of acclimatization is influenced both by the level of altitude and the speed of progression, but is also very individual with a wide spectrum of responses and sensitivities. This wide range of responses is associated with nonspecific symptoms characterising acute mountain sickness and high-altitude cerebral or pulmonary oedema. This article reviews the current knowledge about both the acclimatization processes and specific diseases of high-altitude.

[Cardiac dysfunction and the obstructive sleep apnoea syndrome]. / Dysfonction cardiaque et syndrome d'apnée du sommeil.

INTRODUCTION: Cardiac insufficiency affects nearly 2% of the population with increased morbidity/mortality despite advances in therapeutic management. The sleep apnoea syndrome (SAS) is a risk factor for, and cause of aggravation of, myocardial dysfunction. BACKGROUND: SAS is found in 70% of patients with chronic cardiac failure, 65% of patients with refractory hypertension, 60% of patients with cerebro-vascular accidents and 50% of patients with atrial fibrillation. The associated cardiovascular mortality is multiplied by a factor of 2 to 3. The pathophysiological mechanisms are intermittent nocturnal hypoxia, variations in CO2 levels, variations in intrathoracic pressure and repeated arrousals from sleep, concurrent with sympathetic hyperactivity, endothelial dysfunction and systemic inflammation. CONCLUSIONS: SAS and cardiological management in patients presenting with myocardial dysfunction should be combined. It is necessary to pursue the scientific investigations with the aim of determining a precise care pathway and the respective places of each of the cardiological and pulmonary measures.

[Hepatopulmonary syndrome characteristics in hepatic cirrhosis associated with COPD].

AIM: To evaluate specific features of hepatopulmonary syndrome (HPS) in patients with cirrhosis and cirrhosis associated with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: We made a retrospective analysis of case histories of 75 patients with hepatic cirrhosis (HC) of different etiology. The patients were divided into two groups: 23 patients with HC and COPD (group 1); 52 patients with HC without COPD (group 2). The patients were examined with spirography, gasometry. Single-breath carbon monoxide diffusion capacity (Dlco), TCO and TCO/VA were estimated. Transthoracic contrast-enhanced echocardiography was conducted for detection of intrapulmonary bypass in AaDO2 > 15 mm Hg. RESULTS: COPD stage I and II were diagnosed in 14 of 23 and 9 of 23 patients of group 1, respectively. TCO and TCO/VA had a trend to lowering in group 1 (p > 0.05). PaO2 was lower (p < 0.05) while AaDO2 was higher (p < 0.05) in group 1. Four patients of group I had intrapulmonary bypasses: of the first degree (2 patients with hypoxemia) and of the first and second degree (2 patients with normoxemia). In group 2 three patients had intrapulmonary bypasses: of the fourth degree in 1 patient with hypoxemia and of the first and second degree in 2 patients with normoxemia. CONCLUSION: HC patients with COPD had more severe hypoxemia. Mild and moderate HPS were registered in both groups. In COPD the risk of HPS is 3 times higher.

Does circulating BNP normalize after heart transplantation in patients with normal hemodynamic and right and left heart functions?

BACKGROUND: Increased brain natriuretic peptide (BNP) in cardiovascular disease is thought to be a compensatory protective mechanism allowing to delay the occurrence of terminal heart failure. Heart transplantation should normalize the neuroendocrine balance but BNP remains elevated in stable heart-transplant recipients (Htx). Such increase has been related to persistent endothelial and cardiac dysfunctions. The purpose of this study was to determine whether selected Htx, presenting with normal hemodynamic and cardiac systolic and diastolic functions on both side of the heart, show a normalization of their BNP plasma values. METHODS: Of a cohort of well-being 26 Htx, we selected 12 patients with normal hemodynamics and left and right heart systolic and diastolic functions and compared their circulating BNP, cyclic guanosine monophosphate (cGMP) (the BNP second messenger) and endothelin-1 (ET) values with that of 12 age-, body mass index- and mean arterial pressure-matched controls. Cardiac function determination by echodoppler included cardiac filling pressures assessment using tissue Doppler imaging. Blood samples for biological and hormonal determinations were drawn at rest, within 15 min before echocardiography. RESULTS: As selected, hemodynamic and left and right heart systolic and diastolic functions were located in the normal range in Htx. Plasma ET value was also similar in Htx and controls (20.7 +/- 0.9 vs. 19.6 +/- 0.9 fmol/mL). However, circulating BNP, like cGMP, was still significantly increased after heart transplantation, when compared with controls (33.8 +/- 8.5 vs. 4.0 +/- 0.9 pg/mL, p = 0.002 and 8.2 +/- 1.1 vs. 4.4 +/- 0.3 nmol/L, p = 0.003) for BNP and cGMP, respectively, in Htx and controls. Interestingly, the sole correlation observed was between BNP and cGMP (r = 0.85, p < 0.0001) after heart transplantation. CONCLUSIONS: After heart transplantation, BNP remained increased despite the normalization of hemodynamic and cardiac systolic and diastolic functions. This suggests that such endocrine heart stimulation should not be viewed only as a hemodynamic marker in Htx. Further studies will be useful to investigate the role of pro-inflammatory cytokines and whether elevated BNP still possesses antifibrotic properties, further supporting the interest of enhancing its activity after heart transplantation.

[Place of the exercise stress test at the sportsman]. / Place de l'épreuve d'effort chez le sportif.

Is the stress test still part of the useful examinations in the detection of risk heart disease in sports subjects? Should we continue to use it as a surveillance examination in coronary sports patients? Meta-analysis, considering a ST subshift of more than 1mm as a criterion for positivity, underline the low prevalence of abnormal examinations and a significant rate of false-positives. But for the diagnosis of coronary artery disease, it is mainly the evolution of the ST segment to effort or recovery and the occurrence of stress arrhythmias that detect true positivity. When coronary risk is more important (presence of risk factors, resumption of sport, intense and prolonged efforts), it seems lawful to recommend such a review on a regular basis among men over 40 years of age with two risk factors but Also among veterans taking up sport after a period of prolonged inactivity. For the asymptomatic coronary athlete the stress test remains at the centre of the final decision for the resumption of a sport in competition irrespective of the method of revascularization. Of course the stress test, even inevitable, remains flawed in the detection of coronary artery disease in the asymptomatic athlete. However, it provides additional information on the condition of being maximal, and attaching importance to arrhythmias, the tensional profile and the maximum power developed in addition to the ST segment's only study.

Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?

Central nervous system diseases are among the most disabling in the world. Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation as pharmacology treatments are often insufficiently effective. Conditioning the central nervous system has been proposed as a potential non-pharmacological neuro-therapeutic. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic conditioning has been investigated in several cellular and preclinical models and is now recognized as inducing endogenous mechanisms of neuroprotection. Ischemic, traumatic, or chronic neurodegenerative diseases can benefit from hypoxic conditioning strategies aiming at preventing the deleterious consequences or reducing the severity of the pathological condition (preconditioning) or aiming at inducing neuroplasticity and recovery (postconditioning) following central nervous system injury. Hypoxic conditioning can consist in single (sustained) or cyclical (intermittent, interspersed by short period of normoxia) hypoxia stimuli which duration range from few minutes to several hours and that can be repeated over several days or weeks. This mini-review addresses the existing evidence regarding the use of hypoxic conditioning as a potential innovating neuro-therapeutic modality to induce neuroprotection, neuroplasticity and brain recovery. This mini-review also emphasizes issues which remain to be clarified and future researches to be performed in the field. Impact statement Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation. Hypoxic conditioning may represent a harmless and efficient non-pharmacological new therapeutic modality in the field of neuroprotection and neuroplasticity, as supported by many preclinical data. Animal studies provide clear evidence for neuroprotection and neuroplasticity induced by hypoxic conditioning in several models of neurological disorders. These studies show improved functional outcomes when hypoxic conditioning is applied and provides important information to translate this intervention to clinical practice. Some studies in humans provide encouraging data regarding the tolerance and therapeutic effects of hypoxic conditioning strategies. The main issues to address in future research include the definition of the appropriate hypoxic dose and pattern of exposure, the determination of relevant physiological biomarkers to assess the effects of the treatment and the evaluation of combined strategies involving hypoxic conditioning and other pharmacological or non-pharmacological treatments.

Abnormal heart rate variability in a subject with second degree atrioventricular blocks during sleep.

OBJECTIVE: We compare the profiles of heart rate variability (HRV) during sleep stages in 9 healthy controls and one subject with second degree atrioventricular blocks (AVB), investigating the role of sympathovagal balance in such pathology. METHOD: Sleep and cardiac records were taken for one night in 9 male subjects from 21:00 to 07:00 h and for two nights in a male subject with AVB. Time and frequency domain indexes of HRV were calculated over 5 min-periods. RESULTS: In one subject without any daytime heart disease, 253 and 318 AVB of type 2 (Mobitz 2) were observed during the two experimental nights, predominantly during rapid eye movement (REM) sleep and the surrounding sleep stage 2 in the second half of the night. In the 9 control subjects, absolute HRV indexes and low frequency (LF)/(LF+high frequency, HF) (where LF and HF are low frequency and high frequency power) were low during slow wave sleep, and significantly increased during REM sleep and the preceding sleep stage 2. In the subject with AVB, these HRV indexes were abnormally low during all sleep stages, with a predominant increase in parasympathetic activity as inferred from low LF/(LF+HF). During wake, however, LF/(LF+HF) normally increased, and the tachycardia observed with the arousal that terminates SWS was preserved in the subject with AVB. CONCLUSION: These results suggest that in the subject with second degree atrioventricular blocks, sleep processes, particularly during REM sleep, create a specific neurological background that prevents an increase in sympathetic tone and triggers cardiac pauses.

Muscle phosphorylase kinase deficiency: a neutral metabolic variant or a disease?

OBJECTIVE: To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD). METHODS: Patient 1 (39 years old) had mild exercise-induced forearm pain, and EMG showed a myopathic pattern. Patient 2 (69 years old) had raised levels of creatine kinase (CK) for more than 6 months after statin treatment. Both patients had increased glycogen levels in muscle and PHK activity <11% of normal. Two novel pathogenic nonsense mutations were found in the PHKA1 gene. The metabolic response to anaerobic forearm exercise and aerobic cycle exercise was studied in the patients and 5 healthy subjects. RESULTS: Ischemic exercise showed a normal 5-fold increase in plasma lactate (peak 5.7 and 6.9 mmol/L) but an exaggerated 5-fold increase in ammonia (peak 197 and 171 µmol/L; control peak range 60-113 µmol/L). An incremental exercise test to exhaustion revealed a blunted lactate response (5.4 and 4.8 mmol/L) vs that for control subjects (9.6 mmol/L; range 7.1-14.3 mmol/L). Fat and carbohydrate oxidation rates at 70% of peak oxygen consumption were normal. None of the patients developed a second wind phenomenon or improved their work capacity with an IV glucose infusion. CONCLUSION: Our findings demonstrate that muscle PHK deficiency may present as an almost asymptomatic condition, despite a mild impairment of muscle glycogenolysis, raised CK levels, and glycogen accumulation in muscle. The relative preservation of glycogenolysis is probably explained by an alternative activation of myophosphorylase by AMP and P(i) at high exercise intensities.

Relationship between very high physical activity energy expenditure, heart rate variability and self-estimate of health status in middle-aged individuals.

In middle-aged persons, moderate physical activity energy expenditure (PAEE) has been shown to be associated with increased vagal-related heart rate variability (HRV) indexes and better health status. The purpose of this study was to determine whether a very high PAEE has greater effect on vagal-related HRV indexes and self-estimates of well-being in middle-aged subjects having distinct long-term physical activity profiles. Forty-four subjects were divided into three groups on the basis of the sport score of the Modified Baecke Questionnaire for Older Adults: sedentary (SED, n = 15), moderately-trained (MT, n = 16), and highly-trained subjects (HT, n = 13). PAEE was estimated by triaxial accelerometry during one week. Time and frequency domain HRV indexes were determined during quiet periods in the morning on 5-min R-R interval segments under controlled breathing. Quality of life was evaluated using the SF-36 health survey questionnaire. PAEE was significantly different for each group (374.5 +/- 13.8, 616.8 +/- 22.4, and 1086.6 +/- 43.2 kcal . day (-1) for SED, MT, and HT, respectively, p < 0.001). MT presented significantly higher vagal-related HRV indexes than SED and HT (p < 0.05). None of the HRV indexes was significantly greater in HT than in SED. MT and HT had similar health status scores, which were significantly higher than for SED. These results indicate that in middle-aged subjects, habitual moderate PAEE is associated with greater vagal tone and self-estimates of well-being compared to low PAEE. In contrast, very high PAEE is associated with similar vagal-related indexes as low PAEE, despite better overall health status.