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Purpose We tested the vagal withdrawal concept for heart rate (HR) and cardiac output (CO) kinetics upon moderate exercise onset, by analysing the effects of vagal blockade on cardiovascular kinetics in humans. We hypothesized that, under atropine, the φ1 amplitude (A1) for HR would reduce to nil, whereas the A1 for CO would still be positive, due to the sudden increase in stroke volume (SV) at exercise onset. Methods On nine young non-smoking men, during 0–80 W exercise transients of 5-min duration on the cycle ergometer, preceded by 5-min rest, we continuously recorded HR, CO, SV and oxygen uptake ($$ \dot{V} $$ V ˙ O2) upright and supine, in control condition and after full vagal blockade with atropine. Kinetics were analysed with the double exponential model, wherein we computed the amplitudes (A) and time constants (τ) of phase 1 (φ1) and phase 2 (φ2). Results In atropine versus control, A1 for HR was strongly reduced and fell to 0 bpm in seven out of nine subjects for HR was practically suppressed by atropine in them. The A1 for CO was lower in atropine, but not reduced to nil. Thus, SV only determined A1 for CO in atropine. A2 did not differ between control and atropine. No effect on τ1 and τ2 was found. These patterns were independent of posture. Conclusion The results are fully compatible with the tested hypothesis. They provide the first direct demonstration that vagal blockade, while suppressing HR φ1, did not affect φ1 of CO.

Alessia Riglietti,1,* Francesco Fanfulla,2,* Massimo Pagani,3 Daniela Lucini,3,4 Mara Malacarne,3,4 Mauro Manconi,5– 7 Guido Ferretti,8,9 Fabio Esposito,10,11 Carlo W Cereda,12 Marco Pons1 1Department of Pulmonology, Regional Hospital of Lugano (EOC), Lugano, 6900, Switzerland; 2Respiratory Function and Sleep Unit – Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; 3Exercise Medicine Unit, Istituto Auxologico Italiano, MIlan, 20133, Italy; 4University of Milan, BIOMETRA Department, Milan, Italy; 5Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Regional Hospital (EOC) of Lugano, Lugano, Switzerland; 6Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; 7Department of Neurology, University Hospital, Inselspital, Bern, Switzerland; 8Department APSI, University of Geneva, Geneva, Switzerland; 9Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; 10Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy; 11IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 12Stroke Center EOC, Department of Neurology, Neurocenter of Southern Switzerland Regional Hospital (EOC) of Lugano, Lugano, Switzerland*These authors contributed equally to this workCorrespondence: Mauro ManconiRegional Hospital of Lugano, Via Tesserete, 46, Lugano, 6903, SwitzerlandTel +41-91-8116825Email mauro.manconi@eoc.chIntroduction: Sleep-related breathing disorders are highly prevalent in patients with ischemic stroke. Among sleep-disordered breathing disorders, obstructive sleep apnea is the most represented one, but central sleep apnea, isolated or in the context of a periodic breathing/Cheyne–Stokes respiration, is frequently reported in these patients. Altered baroreflex responses have been reported in the acute phases of a cerebral event.Methods: We conducted, in a group of patients with ischemic stroke (n=60), a prospective 3-month follow-up physiological study to describe the breathing pattern during sleep and baroreflex sensitivity in the acute phase and in the recovery phase.Results: In the acute phase, within 10 days from the onset of symptoms, 22.4% of patients had a normal breathing pattern, 40.3% had an obstructive pattern, 16.4% had a central pattern, and 29.9% showed a mixed pattern. Smaller variations in the Apnea–Hypopnea Index were found in normal breathing and obstructive groups (ΔAHI 2.1± 4.1 and − 2.8± 11.6, respectively) in comparison with central and mixed patterns (ΔAHI − 6.9± 15.1 and − 12.5± 13.1, respectively; ANOVA p=0.01). The obstructive pattern became the most frequent pattern, in 38.3% of patients at baseline and 61.7% of patients at follow-up. Modification of baroreflex sensitivity over time was influenced by the site of the lesion and by the sleep disorder pattern in the acute phase (MANOVA p=0.005).Conclusion: We suggest that a down-regulation of autonomic activity, possibly related to reduced vagal modulation, may help the recovery after stroke, or a transitory disconnection from the cortical node that participates in the regulation of sympathetic outflow.Keywords: sleep-disordered breathing, baroreflex, chemoreflex, brain lesion

Introduction Measuring physiological parameters at depth is an emergent challenge for athletic training, diver's safety and biomedical research. Recent advances in wearable sensor technology made this challenge affordable; however, its impact on breath-hold diving has never been comprehensively discussed. Methods We performed a systematic review of the literature in order to assess what types of sensors are available or suitable for human breath-hold diving, within the two-fold perspective of safety and athletic performance. Results In the 52 studies identified, sensed physiological variables were: electrocardiogram, body temperature, blood pressure, peripheral oxygen saturation, interstitial glucose concentration, impedance cardiography, heart rate, body segment inertia and orientation. Conclusions Limits and potential of each technology are separately reviewed. Inertial sensor technology and transmission pulse oximetry could produce the greatest impact on breath-hold diving performances in the future.

We hypothesized that during rapid uptilting at rest, due to vagal withdrawal, arterial baroreflex sensitivity (BRS) may decrease promptly and precede the operating point (OP) resetting, whereas different kinetics are expected during exercise steady state, due to lower vagal activity than at rest. To test this, eleven subjects were rapidly (−1 (SD = 17.1) in S and 16.7 ms·mmHg−1 (SD = 6.4) in U ( P < 0.01), RRi was 901 ms (SD = 118) in S and 749 ms (SD = 98) in U ( P < 0.01), and MAP was 76 mmHg (SD = 11) in S and 83 mmHg (SD = 8) in U ( P < 0.01). During uptilt, BRS decreased promptly [first BRS sequence was 19.7 ms·mmHg−1 (SD = 5.0)] and was followed by an OP resetting (MAP increase without changes in RRi). At exercise, BRS and OP did not differ between supine and upright positions [BRS was 7.7 ms·mmHg−1 (SD = 3.0) and 7.7 ms·mmHg−1 (SD = 3.5), MAP was 85 mmHg (SD = 13) and 88 mmHg (SD = 10), and RRi was 622 ms (SD = 61) and 600 ms (SD = 70), respectively]. The results support the tested hypothesis. The prompt BRS decrease during uptilt at rest may be ascribed to a vagal withdrawal, similarly to what occurs at exercise onset. The OP resetting may be due to a slower control mechanism, possibly an increase in sympathetic activity.

New findings What is the central question of this study? We modelled the alveolar pathway during breath holding on the hypothesis that it follows a hypoventilation loop on the O2 -CO2 diagram. What is the main finding and its importance? Validation of the model was possible within the range of alveolar gas compositions compatible with consciousness. Within this range, the experimental data were compatible with the proposed model. The model and its characteristics might allow predictions of alveolar gas composition whenever the alveolar ventilation goes to zero; for example, static and dynamic breath holding at the surface or during ventilation/intubation failure in anaesthesia. Abstract According to the hypothesis that alveolar partial pressures of O2 and CO2 during breath holding (BH) should vary following a hypoventilation loop, we modelled the alveolar gas pathways during BH on the O2 -CO2 diagram and tested it experimentally during ambient air and pure oxygen breathing. In air, the model was constructed using the inspired and alveolar partial pressures of O2 ( P I O 2 and P A O 2 , respectively) and CO2 ( P IC O 2 and P AC O 2 , respectively) and the steady-state values of the pre-BH respiratory exchange ratio (RER). In pure oxygen, the model respected the constraint of P AC O 2 = - P A O 2 + P I O 2 . To test this, 12 subjects performed several BHs of increasing duration and one maximal BH at rest and during exercise (30 W cycling supine), while breathing air or pure oxygen. We measured gas flows, P A O 2 and P AC O 2 before and at the end of all BHs. Measured data were fitted through the model. In air, P I O 2 = 150 ± 1 mmHg and P IC O 2 = 0.3 ± 0.0 mmHg, both at rest and at 30 W. Before BH, steady-state RER was 0.83 ± 0.16 at rest and 0.77 ± 0.14 at 30 W; P A O 2 = 107 ± 7 mmHg at rest and 102 ± 8 mmHg at 30 W; and P AC O 2 = 36 ± 4 mmHg at rest and 38 ± 3 mmHg at 30 W. By model fitting, we computed the RER during the early phase of BH: 0.10 [95% confidence interval (95% CI) = 0.08-0.12] at rest and 0.13 (95% CI = 0.11-0.15) at 30 W. In oxygen, model fitting provided P I O 2 : 692 (95% CI = 688-696) mmHg at rest and 693 (95% CI = 689-698) mmHg at 30 W. The experimental data are compatible with the proposed model, within its physiological range.

Purpose We analysed the characteristics of arterial baroreflexes during the first phase of apnoea (φ1). Methods 12 divers performed rest and exercise (30 W) apnoeas (air and oxygen). We measured beat-by-beat R-to-R interval (RRi) and mean arterial pressure (MAP). Mean RRi and MAP values defined the operating point (OP) before (PRE-ss) and in the second phase (φ2) of apnoea. Baroreflex sensitivity (BRS, ms·mmHg−1) was calculated with the sequence method. Results In PRE-ss, BRS was (median [IQR]): at rest, 20.3 [10.0–28.6] in air and 18.8 [13.8–25.2] in O2; at exercise 9.2[8.4–13.2] in air and 10.1[8.4–13.6] in O2. In φ1, during MAP decrease, BRS was lower than in PRE-ss at rest (6.6 [5.3–11.4] in air and 7.7 [4.9–14.3] in O2, p 2. After attainment of minimum MAP (MAPmin), baroreflex resetting started. After attainment of minimum RRi, baroreflex sequences reappeared. In φ2, BRS at rest was 12.1 [9.6–16.2] in air, 12.9 [9.2–15.8] in O2. At exercise (no φ2 in air), it was 7.9 [5.4–10.7] in O2. In φ2, OP acts at higher MAP values. Conclusion In apnoea φ1, there is a sudden correction of MAP fall via baroreflex. The lower BRS in the earliest φ1 suggests a possible parasympathetic mechanism underpinning this reduction. After MAPmin, baroreflex resets, displacing its OP at higher MAP level; thus, resetting may not be due to central command. After resetting, restoration of BRS suggests re-establishment of vagal drive.

We hypothesised that vagal withdrawal and increased venous return interact in determining the rapid cardiac output (CO) response (phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood distribution to the heart by muscle pump action and reduce resting vagal activity. We expected a larger increase in stroke volume (SV) and smaller for heart rate (HR) at progressively stronger LBNP levels, therefore CO response would remain unchanged. To this aim ten young, healthy males performed a 50 W exercise in supine position at 0 (Control), −15, −30 and −45 mmHg LBNP exposure. On single beat basis, we measured HR, SV, and CO. Oxygen uptake was measured breath-by-breath. Phase I response amplitudes were obtained applying an exponential model. LBNP increased SV response amplitude threefold from Control to −45 mmHg. HR response amplitude tended to decrease and prevented changes in CO response. The rapid response of CO explained that of oxygen uptake. The rapid SV kinetics at exercise onset is compatible with an increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, one acting on SV, the other on HR.

The effects of lung afferents denervation on cardiovascular regulation can be assessed on bilateral lung transplantation patients. The high-frequency component of heart rate variability is known to be synchronous with breathing frequency. Then, if heart beat is neurally modulated by breathing frequency, we may expect disappearance of high frequency of heart rate variability in bilateral lung transplantation patients. On 11 patients and 11 matching healthy controls, we measured R-R interval (electrocardiography), blood pressure (Portapres® ) and breathing frequency (ultrasonic device) in supine rest, during 10-min free breathing, 10-min cadenced breathing (0·25 Hz) and 5-min handgrip. We analysed heart rate variability and spontaneous variability of arterial blood pressure, by power spectral analysis, and baroreflex sensitivity, by the sequence method. Concerning heart rate variability, with respect to controls, transplant recipients had lower total power and lower low- and high-frequency power. The low-frequency/high-frequency ratio was higher. Concerning systolic, diastolic and mean arterial pressure variability, transplant recipients had lower total power (only for cadenced breathing), low frequency and low-frequency/high-frequency ratio during free and cadenced breathing. Baroreflex sensitivity was decreased. Denervated lungs induced strong heart rate variability reduction. The higher low-frequency/high-frequency ratio suggested that the total power drop was mostly due to high frequency. These results support the hypothesis that neural modulation from lung afferents contributes to the high frequency of heart rate variability.

Objective. Total lung capacity (TLC) assessment outside of a research laboratory is challenging. We describe a novel method for measuring TLC that is both simple and based only on portable equipment, and report preliminary data in healthy subjects.Approach. We developed an open circuit system to administer a known amount of oxygen to a subject in a single maximal inspiratory maneuver. Oxygen fraction, expired and inspired flows were continuously monitored to allow a precise computation of the mass balance. Values of TLC and functional residual capacity (FRC) were compared with standard methods (body plethysmography and multiple-breath helium dilution). Twenty healthy subjects participated to the study, eleven of which performed the maneuver twice to assess test-retest reliability.Main results.There was high agreement in TLC between the proposed method and the two standard methods (R2 > 0.98, bias not different from 0, and 95% limits of agreements 0.99 and no bias). Results were similar for FRC, with a slightly higher variability due its sensitivity to changes in posture or breathing pattern.Significance.Single-breath oxygen dilution is accurate and reliable in assessing TLC and FRC in healthy subjects. The technique is appealing for time- or resource-limited settings, such as field physiological research expeditions or mass screenings.

To check whether the evolution of alveolar pressures of O2 (PAO2) and CO2 (PACO2) explains the cardiovascular responses to apnoea, eight divers performed resting apnoeas of increasing duration in air and in O2. We measured heart rate (fH), arterial pressure (AP), and peripheral resistances (TPR) beat-by-beat, PAO2 and PACO2 at the end of each apnoea. The three phases of the cardiovascular response to apnoea were observed. In O2, TPR increase (9 ± 4 mmHg min l−1) and fH decrease (-11 ± 8 bpm) were lower than in air (15 ± 5 mmHg min l−1 and -28 ± 13 bpm, respectively). At end of maximal apnoeas in air, PAO2 and PACO2 were 50 ± 9 and 48 ± 5 mmHg, respectively; corresponding values in O2 were 653 ± 8 mmHg and 55 ± 5 mmHg. At end of phase II, PAO2 and PACO2 in air were 90 ± 13 mmHg and 42 ± 4 mmHg respectively; corresponding values in O2 were 669 ± 7 mmHg and 47 ± 6 mmHg. The PACO2 increase may trigger the AP rise in phase III.

A 73-year-old man with a prostate cancer treated by radical prostatectomy in 2006. For a biochemical recurrence of disease (prostate-specific antigen level, 0.1 ng/mL) during hormonal therapy, patient underwent F-choline PET/CT that showed a significant uptake in a diffuse right pleural thickening. The patient was sent to pleurectomy decortication showing an epithelioid pleural mesothelioma. This case highlighted that a histopathological evaluation is mandatory in case of a significant radiolabeled choline uptake in pleural lesions.

We report a case of a 74-year-old woman who presented to the hospital for fever and uncontrolled hypertension. We found, incidentally, a giant aneurysm of the circumflex coronary artery measuring 6.4×5.5 cm. We show suggestive computed tomographic scan images, multi-slice reconstructions and a review of the epidemiology, diagnosis and treatment of this condition.

The aim of this paper was to develop a model from experimental data allowing a prediction of the cardiopulmonary responses to steady-state submaximal exercise in varying gravitational environments, with acceleration in the G(z) axis (a (g)) ranging from 0 to 3 g. To this aim, we combined data from three different experiments, carried out at Buffalo, at Stockholm and inside the Mir Station. Oxygen consumption, as expected, increased linearly with a (g). In contrast, heart rate increased non-linearly with a (g), whereas stroke volume decreased non-linearly: both were described by quadratic functions. Thus, the relationship between cardiac output and a (g) was described by a fourth power regression equation. Mean arterial pressure increased with a (g) non linearly, a relation that we interpolated again with a quadratic function. Thus, total peripheral resistance varied linearly with a (g). These data led to predict that maximal oxygen consumption would decrease drastically as a (g) is increased. Maximal oxygen consumption would become equal to resting oxygen consumption when a (g) is around 4.5 g, thus indicating the practical impossibility for humans to stay and work on the biggest Planets of the Solar System.

The baroreflex system is a complex mechanism for short-term regulation of arterial blood pressure, involving the heart rate (HR), the heart contractility and the vascular tone in its efferent branches. The study of arterial baroreflexes relies on two different experimental approaches. On one hand, the closed-loop approach analyses the mutual relationship between HR and arterial blood pressure, both in steady state and in dynamic conditions. This article is protected by copyright. All rights reserved.

If, as postulated, the end of the steady state phase (φ2) of cardiovascular responses to apnoea corresponds to the physiological breaking point, then we may hypothesize that φ2 should become visible if exercise apnoeas are performed in pure oxygen. We tested this hypothesis on 9 professional divers by means of continuous recording of blood pressure (BP), heart rate (fH), stroke volume (QS), and arterial oxygen saturation (SpO2) during dry maximal exercising apnoeas in ambient air and in oxygen. Apnoeas lasted 45.0 ± 16.9 s in air and 77.0 ± 28.9 s in oxygen (p

It is well established that regular physical exercise enhances memory functions, synaptic plasticity in the hippocampus, and BDNF (Brain Derived Neurotrophic Factor) levels. Likewise, acute exercise benefits hippocampal plasticity in rodents, via increased endocannabinoids (especially anandamide, AEA) and BDNF release. Yet, whether acute exercise affects BDNF and AEA levels and influences memory performance in humans, remains to date unknown. Here we combined blood biomarkers, behavioral, and fMRI measurements to assess the impact of acute physical exercise on associative memory and underlying neurophysiological mechanisms. For each participant, memory was tested after three conditions: rest, moderate or high intensity exercise. A long-term memory retest took place 3 months later. At both test and retest, memory performance after moderate intensity exercise was increased compared to rest and high intensity exercise. We also show that memory after moderate intensity exercise benefited from exercise-induced increases in both AEA and BNDF levels: while AEA boosted hippocampal activity during memory recall, BDNF enhanced hippocampal memory representations and long-term performance. These findings confirm previous results on the benefits of acute exercise towards memory consolidation and, by including the contribution of key biomarkers, extend them by explaining neural plasticity mechanisms mediating cognitive enhancement.

Regular physical exercise has been shown to benefit neurocognitive functions, especially enhancing neurogenesis in the hippocampus. However, the effects of a single exercise session on cognitive functions are controversial. To address this issue, we measured hemodynamic changes in the brain during physical exercise using near-infrared spectroscopy (NIRS) and investigated related effects on memory consolidation processes. Healthy young participants underwent two experimental visits. During each visit, they performed an associative memory task in which they first encoded a series of pictures, then spent 30-min exercising or resting, and finally were asked to recall the picture associations. We used NIRS to track changes in oxygenated hemoglobin concentration over the prefrontal cortex during exercise and rest. To characterize local tissue oxygenation and perfusion, we focused on low frequency oscillations in NIRS, also called vasomotion. We report a significant increase in associative memory consolidation after exercise, as compared to after rest, along with an overall increase in vasomotion. Additionally, performance improvement after exercise correlated positively with power in the neurogenic component (0.02 to 0.04 Hz) and negatively with power in the endothelial component (0.003 to 0.02 Hz). Overall, these results suggest that changes in vasomotion over the prefrontal cortex during exercise may promote memory consolidation processes.

Introduction We tested the hypothesis that the alveolar gas composition at the transition between the steady phase II (φ2) and the dynamic phase III (φ3) of the cardiovascular response to apnoea may lay on the physiological breaking point curve (Lin et al., 1974). Methods Twelve elite divers performed maximal and φ2-interrupted apnoeas, in air and pure oxygen. We recorded beat-by-beat arterial blood pressure and heart rate; we measured alveolar oxygen and carbon dioxide pressures (P A O 2 and P A CO 2 , respectively) before and after apnoeas; we calculated the P A CO 2 difference between the end and the beginning of apnoeas (ΔP A CO 2 ). Results Cardiovascular responses to apnoea were similar compared to previous studies. P A O 2 and P A CO 2 at the end of φ2-interrupted apnoeas, corresponded to those reported at the physiological breaking point . For maximal apnoeas, P A CO 2 was less than reported by Lin et al. (1974). ΔP A CO 2 was higher in oxygen than in air. Conclusions The transition between φ2 and φ3 corresponds indeed to the physiological breaking point . We attribute this transition to ΔP A CO 2 , rather than the absolute P A CO 2 values, both in air and oxygen apnoeas.

PURPOSE: The dynamics of the postulated phenomenon of exercise baroreflex resetting is poorly understood, but can be investigated using closed-loop procedures. To shed light on some mechanisms and temporal relationships participating in the resetting process, we studied the time course of the relationship between the R-R interval (RRi) and arterial pressure with a closed-loop approach. METHODS: On ten young volunteers at rest and during light exercise in supine and upright position, we continuously determined, on single-beat basis, RRi (electrocardiography), and arterial pressure (non-invasive finger pressure cuff). From pulse pressure profiles, we determined cardiac output (CO) by Modelflow, computed mean arterial pressure (MAP), and calculated total peripheral resistance (TPR). RESULTS: At exercise start, RRi was lower than in quiet rest. As exercise started, MAP fell to a minimum (MAPm) of 72.8 ± 9.6 mmHg upright and 73.9 ± 6.2 supine, while RRi dropped. The initial RRi versus MAP relationship was linear, with flatter slope than resting baroreflex sensitivity, in both postures. TPR fell and CO increased. After MAPm, RRi and MAP varied in opposite direction toward exercise steady state, with further CO increase. CONCLUSION: These results suggest that, initially, the MAP fall was corrected by a RRi reduction along a baroreflex curve, with lower sensitivity than at rest, but eventually in the same pressure range as at rest. After attainment of MAPm, a second phase started, where the postulated baroreflex resetting might have occurred. In conclusion, the change in baroreflex sensitivity and the resetting process are distinct phenomena, under different control systems.

Cardiovascular responses during resting apnoea include three phases: (1) a dynamic phase of rapid changes, lasting at most 30 s; (2) a subsequent steady phase; and (3) a further dynamic phase, with a continuous decrease in heart rate (HR) and an increase in blood pressure. The interpretation was that the end of the steady phase corresponds to the physiological apnoea breaking point. This being so, during exercise apnoeas, the steady phase would be shorter, and the rate of cardiovascular changes in the subsequent unsteady phase would be faster than at rest. To test these hypotheses, we measured beat-by-beat systolic (SBP), diastolic, and mean blood pressures (MBP), HR, and stroke volume (SV) in six divers during dry resting (duration 239.4 ± 51.6 s) and exercise (30 W on cycle ergometer, duration 88.2 ± 20.9 s) maximal apnoeas, and we computed cardiac output ( $$\dot{Q}$$ ) and total peripheral resistance (TPR). Compared to control, at the beginning of resting (R1) and exercising (E1) apnoeas, SBP and MBP decreased and HR increased. SV and $$\dot{Q}$$ fell, so that TPR remained unchanged. At rest, HR, SV, $$\dot{Q}$$ , and SBP were stable during the subsequent phase; this steady phase was missing in exercise apnoeas. Subsequently, at rest (R3) and at exercise (E2), HR decreased and SBP increased continuously. SV returned to control values. Since $$\dot{Q}$$ remained unchanged, TPR grew. The lack of steady phase during exercise apnoeas suggests that the conditions determining R3 were already attained at the end of E1. This being so, E2 would correspond to R3.

A new analysis of the relationship between cardiac output (Q˙) and oxygen consumption V˙O2 is presented (Q˙-V˙O2 diagram). Data from different sources in the literature have been used for validation in three conditions: exercise and rest in normoxia, and exercise in hypoxia. The effects of changes in arterial oxygen concentration CaO2 on Q˙ are discussed, as well as the effects of predominant sympathetic or vagal stimulation. Differences appear depending on whether CaO2 is varied by means of changes in blood haemoglobin concentration or changes in arterial oxygen saturation. The present Q˙-V˙O2 diagram allows comprehensive description of oxygen transport in exercising humans; it expands applicability of the historical Q˙-V˙O2 relationship to include CaO2 variations; it opens new pathways for understanding underlying mechanisms; it allows computation of Q˙ from CaO2 and V˙O2 measurements, when Q˙ cannot be measured.

We hypothesised that phase II time constant (τ2) of alveolar O2 uptake ( [Formula: see text] ) is longer in hypoxia than in normoxia as a consequence of a parallel deceleration of the kinetics of O2 delivery ( [Formula: see text] ). To test this hypothesis, breath-by-breath [Formula: see text] and beat-by-beat [Formula: see text] were measured in eight male subjects (25.4±3.4yy, 1.81±0.05m, 78.8±5.7kg) at the onset of cycling exercise (100W) in normoxia and acute hypoxia ( [Formula: see text] ). Blood lactate ([La]b) accumulation during the exercise transient was also measured. The τ2 for [Formula: see text] was shorter than that for [Formula: see text] in normoxia (8.3±6.8s versus 17.8±3.1s), but not in hypoxia (31.5±21.7s versus 28.4 5.4±5.4s). [La]b was increased in the exercise transient in hypoxia (3.0±0.5mM at exercise versus 1.7±0.2mM at rest), but not in normoxia. We conclude that the slowing down of the [Formula: see text] kinetics generated the longer τ2 for [Formula: see text] in hypoxia, with consequent contribution of anaerobic lactic metabolism to the energy balance in exercise transient, witnessed by the increase in [La]b.

Purpose.Cardiac output (CO) is a cornerstone parameter in precapillary pulmonary hypertension (PH). The Modelflow (MF) method offers a reliable noninvasive determination of its beat-by-beat changes. So MF allows exploration of CO adjustment with the best temporal resolution.Methods.Fifteen subjects (5 PH patients, 10 healthy controls) performed a submaximal supine exercise on a cycle ergometer after 5 min of rest. CO was continuously determined by MF (COMF). Kinetics of heart rate (HR), stroke volume (SV), and CO were determined with 3 monoexponential models.Results.In PH patients, we observed a sudden and transitory drop of SV upon exercise onset. This implied a transitory drop of CO whose adjustment to a new steady state depended on HR increase. The kinetics of HR and CO for PH patients was slower than that of controls for all models and for SV in model 1. SV kinetics was faster for PH patients in models 2 and 3.Conclusion.This is the first description of beat-by-beat cardiovascular adjustments upon exercise onset in PH. The kinetics of HR and CO appeared slower than those of healthy controls and there was a transitory drop of CO upon exercise onset in PH due to a sudden drop of SV.

Bilateral lung transplantation (BLT) implies full lung denervation. It is an excellent model of cardiovascular regulation without modulation of heart activity by lung afferents. The high frequency (HF) peak of heart rate variability (HRV) is synchronous with breathing frequency (BF). If this comes from neural modulation of the heart beat by BF, HF of HRV should disappear after BLT. The aim of this study was to analyse HRV in BLT as compared with healthy controls (C). 11 BLT (6 women and 5 men), aged 49.0±14.5 yrs and 11 sex- and age-matched healthy controls (C), aged 47.3±14.5, were studied. We recorded heart rate (HR, ECG), blood pressure (Portapres) and BF (ultrasonic device) during 10 min of free breathing at rest, 10 min of cadenced breathing (0.25Hz) at rest, and 5min of handgrip, in supine posture. We evaluated spontaneous variability of HR, and of systolic, diastolic and mean pressure (SAP, DAP and MAP), by power spectral analysis, and baroreflex sensitivity (BRS), by the sequence method. BLT had higher HR, but the same SAP, DAP and MAP than C. BF was higher in BLT than in C during free breathing. BLT showed lower BRS, total power (PTOT), low-frequency peak (LF) and HF than C, in all conditions. The LF/HF ratio was higher in BLT than in C. In normalised units, BLT had higher LF (LFnu) and lower HF (HFnu) than C. Concerning blood pressure, BLT had higher PTOT, LF and HF powers for SAP; higher HF and lower LF/HF for DAP; lower LF/HF for MAP, than C. HRV was reduced in BLT. A higher LF/HF ratio implies that the PTOT drop was mostly due to HF. The reverse was the case for SAP. The results are compatible with the hypothesis that neural modulation from lung afferents contributes to the HF component of HRV.

To assess the effects of respiratory muscle training (RMT) on maximum oxygen uptake (VO2max) in normoxia and hypoxia, 9 healthy males (age 24 +/- 4 years; stature 1.75 +/- 0.08 m; body mass 72 +/- 9 kg; mean +/- SD) performed on different days maximal incremental tests on a cycle ergometer in normoxia and normobaric hypoxia (FIO2=0.11), before and after 8 weeks of RMT (5 days/week). During each test, gas exchange variables were measured breath-by-breath by a metabolimeter. After RMT, no changes in cardiorespiratory and metabolic variables were detected at maximal exercise in normoxia. On the contrary, in hypoxia expired and alveolar ventilation (V(E(and V(A), respectively) at maximal exercise were significantly higher than pre-training condition (+12 and +13%, respectively; P < 0.05). Accordingly, alveolar O2 partial pressure (PAO2) after RMT significantly increased by approximately 10%. Nevertheless, arterial PO2 and VO2max did not change with respect to pre-training condition. In conclusion, RMT improved respiratory function but did not have any effect on VO2max, neither under normoxic nor hypoxic condition. In hypoxia, the significant increase in V(E) and V(A) at maximum exercise after training lead to higher alveolar but not arterial PO2 values, revealing an increased A-a gradient. This result, according to the theoretical models of VO2max limitation, seems to contradict the lack of VO2max increase in hypoxia, suggesting a possible role of increased ventilation-perfusion mismatch.

\( {{\dot{V}O}}_{2} , \)fH, \( \dot{Q}, \) SV, [Hb], CaO2, \( {{\dot{Q}}}_{\text{a}} \)O2, MAP and RP were measured in 10 young subjects at rest and during exercise at 50, 100 and 150 W before and after 14 days of head-down tilt bed rest (HDTBR) and of ambulatory (AMB) control period. fH was 18 and 8% higher after HDTBR and AMB, respectively. SV dropped by 15% both after HDTBR and AMB, whereas \( \dot{Q} \) did not change. After HDTBR, CaO2 decreased at rest (−8%) and at 50 W (−5%), whereas \( {{\dot{Q}}}_{\text{a}} \)O2 did not change; MAP was 14 and 6% lower at rest and at 100 W and RP decreased by 23% only at rest. Changes in fH and SV were larger after HDTBR than after AMB. These results show that, notwhistanding the drop of SV, moderate-intensity dynamic exercise elicited a normal pressure response after 14 days of HDTBR.

The aim of this study was to test the hypothesis that the maximal instantaneous muscular power of humans ( $$ \dot{w} $$ p) is affected by the negative work performed immediately before the jump (w n), possibly due to the recoil of elastic strain energy stored in previously stretched series-elastic elements of the muscle–tendon complex. Twenty-seven Bantu subjects (age 25.1 ± 4.3 years, body mass 67.5 ± 7.8 kg) were investigated. The $$ \dot{w} $$ p, the average power ( $$ \dot{w} $$ a) and w n were determined during maximal vertical jumps off both feet on a force platform. Three jumping conditions were studied: squat jumps (SQ), countermovement jumps (CM), and jumps preceded by a free fall (FF) from a height of 0.3 m above the platform surface. The w n was higher in CM than in SQ and in FF than in CM and SQ. The $$ \dot{w} $$ p was 3.51 ± 0.54 kW in SQ and did not vary in CM and FF. The $$ \dot{w} $$ a increased with increasing w n (1.70 ± 0.30; 1.85 ± 0.34; 1.99 ± 0.31 kW in SQ, CM and FF, respectively, p

Background Cardiac output (CO) is a major diagnostic and prognostic factor in pre-capillary pulmonary hypertension (PH). Reference methods for CO determination, like thermodilution (TD), require invasive procedures and allow only steady-state measurements. The Modelflow (MF) method is an appealing technique for this purpose as it allows non-invasive and beat-by-beat determination of CO. Methods We aimed to compare CO values obtained simultaneously from non-invasive pulse wave analysis by MF (COMF) and by TD (COTD) to determine its precision and accuracy in pre-capillary PH. The study was performed on 50 patients with pulmonary arterial hypertension (PAH) or chronic thrombo-embolic PH (CTEPH). CO was determined at rest in all patients (n = 50) and during nitric oxide vasoreactivity test, fluid challenge or exercise (n = 48). Results Baseline COMF and COTD were 6.18 ± 1.95 and 5.46 ± 1.95 L·min-1, respectively. Accuracy and precision were 0.72 and 1.04 L·min-1, respectively. Limits of agreement (LoA) ranged from -1.32 to 2.76 L·min-1. Percentage error (PE) was ±35.7%. Overall sensitivity and specificity of COMF for directional change were 95.2% and 82.4%, (n = 48) and 93.3% and 100% for directional changes during exercise (n = 16), respectively. After application of a correction factor (1.17 ± 0.25), neither proportional nor fixed bias was found for subsequent CO determination (n = 48). Accuracy was -0.03 L·min−1 and precision 0.61 L·min−1. LoA ranged from -1.23 to 1.17 L·min−1 and PE was ±19.8%. Conclusions After correction against a reference method, MF is precise and accurate enough to determine absolute values and beat-by-beat relative changes of CO in pre-capillary PH.

We hypothesized that the third dynamic phase (ϕ3) of the cardiovascular response to apnoea requires attainment of the physiological breaking point, so that the duration of the second steady phase (ϕ2) of the classical cardiovascular response to apnoea, though appearing in both air and oxygen, is longer in oxygen.Nineteen divers performed maximal apnoeas in air and oxygen. We measured beat-by-beat arterial pressure, heart rate (fH), stroke volume (SV), cardiac output (Q˙).The fH, SV and Q˙ changes during apnoea followed the same patterns in oxygen as in air. Duration of steady ϕ2 was 105 ± 37 and 185 ± 36 s, in air and oxygen (p0.05), respectively. At end of apnoea, arterial oxygen saturation was 1.00 ± 0.00 in oxygen and 0.75 ± 0.10 in air.The results support the tested hypothesis. Lack of hypoxaemia during oxygen apnoeas suggests that, if chemoreflexes determine ϕ3, the increase in CO2 stores might play a central role in eliciting their activation.

The aim of this study was to characterize the time course of maximal oxygen consumption VO2(max) changes during bedrests longer than 30 days, on the hypothesis that the decrease in VO2(max) tends to asymptote. On a total of 26 subjects who participated in one of three bedrest campaigns without countermeasures, lasting 14, 42 and 90 days, respectively, VO2(max) maximal cardiac output (Qmax) and maximal systemic O2 delivery (QaO2max) were measured. After all periods of HDT, VO2max, Qmax, and QaO2max were significantly lower than before. The VO2max decreased less than qmax after the two shortest bedrests, but its per cent decay was about 10% larger than that of Qmax after 90-day bedrest. The VO2max decrease after 90-day bedrest was larger than after 42- and 14-day bedrests, where it was similar. The Qmax and QaO2max declines after 90-day bedrest was equal to those after 14- and 42-day bedrest. The average daily rates of the VO2max, Qmax, and QaO2max decay during bedrest were less if the bedrest duration were longer, with the exception of that of VO2max in the longest bedrest. The asymptotic VO2max decay demonstrates the possibility that humans could keep working effectively even after an extremely long time in microgravity. Two components in the VO2max decrease were identified, which we postulate were related to cardiovascular deconditioning and to impairment of peripheral gas exchanges due to a possible muscle function deterioration.

We tested whether the kinetics of systemic O2 delivery (Q̇aO2) at exercise start was faster than that of lung O2 uptake (V̇o2), being dictated by that of cardiac output (Q̇), and whether changes in Q̇ would explain the postulated rapid phase of the V̇o2 increase. Simultaneous determinations of beat-by-beat (BBB) Q̇ and Q̇aO2, and breath-by-breath V̇o2 at the onset of constant load exercises at 50 and 100 W were obtained on six men (age 24.2 ± 3.2 years, maximal aerobic power 333 ± 61 W). V̇o2 was determined using Grønlund's algorithm. Q̇ was computed from BBB stroke volume (Qst, from arterial pulse pressure profiles) and heart rate ( fh, electrocardiograpy) and calibrated against a steady-state method. This, along with the time course of hemoglobin concentration and arterial O2 saturation (infrared oximetry) allowed computation of BBB Q̇aO2. The Q̇, Q̇aO2 and V̇o2 kinetics were analyzed with single and double exponential models. fh, Qst, Q̇, and V̇o2 increased upon exercise onset to reach a new steady state. The kinetics of Q̇aO2 had the same time constants as that of Q̇. The latter was twofold faster than that of V̇o2. The V̇o2 kinetics were faster than previously reported for muscle phosphocreatine decrease. Within a two-phase model, because of the Fick equation, the amplitude of phase I Q̇ changes fully explained the phase I of V̇o2 increase. We suggest that in unsteady states, lung V̇o2 is dissociated from muscle O2 consumption. The two components of Q̇ and Q̇aO2 kinetics may reflect vagal withdrawal and sympathetic activation.

The objectives to determine both the contribution to orthostatic intolerance (OI) of calf venous volume during a stand-test, and the effects of a combined eccentric-concentric resistance exercise countermeasure on both vein response to orthostatic test and OI, after 90-day head-down tilt bed-rest (HDT). The subjects consisted of a control group (Co-gr, n = 9) and an exercise countermeasure group (CM-gr, n = 9). Calf volume and vein cross-sectional area (CSA) were assessed by plethysmography and echography during pre- and post-HDT stand-tests. From supine to standing (post-HDT), the tibial and gastrocnemius vein CSA increased significantly in intolerant subjects (tibial vein, +122% from pre-HDT; gastrocnemius veins, +145%; P < 0.05) whereas it did not in tolerant subjects. Intolerant subjects tended to have a higher increase in calf filling volume than tolerant subjects, in both sitting and standing positions. The countermeasure did not reduce OI. Absolute calf volume decreased similarly in both groups. Tibial and gastrocnemius vein CSA at rest did not change during HDT in either group. During the post-HDT stand-test, the calf filling volume increased more in the CM-gr than in the Co-gr both in the sitting (+1.3 +/- 5.1%, vs. -7.3 +/- 4.3%; P < 0.05) and the standing positions (+56.1 +/- 23.7% vs. +1.6 +/- 9.6%; P < 0.05). The volume ejected by the muscle venous pump increased only in the CM-gr (+38.3 +/- 21.8%). This study showed that intolerant subjects had a higher increase in vein CSA in the standing position and a tendency to present a higher calf filling volume in the sitting and standing positions. It also showed that a combined eccentric-concentric resistance exercise countermeasure had no effects on either post-HDT OI or on the venous parameters related to it.

Several features of potential adaptation to breath-hold diving in diving populations and extreme divers are reviewed. Thermal adaptation consists of an improvement in cold tolerance, as witnessed by a decrease in critical water temperature, and implies an elevation of the shivering threshold associated with a greater body insulation. This is indicative of either a strong peripheral vasoconstriction or a more effective countercurrent heat exchange. Respiratory adaptation consists of a blunted ventilatory response to carbon dioxide and an enlargement of lung volumes. Finally, the occurrence of a diving response has been demonstrated. An extreme peripheral vasoconstriction is associated with a dramatic increase in arterial blood pressure. The consequent stimulation of arterial baroreceptors causes an extreme drop of heart rate. Bradycardia is not compensated by a higher stroke volume, with consequent decrease in cardiac output. This decrease, however, is not such as to undermine perfusion to vital organs. Redistribution of blood flow occurs, and some organs such as skeletal muscle may become unperfused, as indicated by the high blood lactate concentrations at low metabolic rate. It is not possible to state, however, whether these changes reflect genetic adaptations or an adaptive response to a prolonged environmental stress.

The hypothesis was tested that prolonged bed rest impairs O2 transport during exercise, which implies a lowering of cardiac output Qc and O2 delivery (QaO2). The following parameters were determined in five males at rest and at the steady-state of the 100-W exercise before (B) and after (A) 42-day bed rest with head-down tilt at -6 degrees: O2 consumption (VO2), by a standard open-circuit method; Qc, by the pressure pulse contour method, heart rate (fc), stroke volume (Qh), arterial O2 saturation, blood haemoglobin concentration ([Hb]), arterial O2 concentration (CaO2), and QaO2. The VO2 was the same in A and in B, as was the resting fc. The fc at 100 W was higher in A than in B (+17.5%). The Qh was markedly reduced (-27.7% and -22.2% at rest and 100 W, respectively). The Qc was lower in A than in B [-27.6% and -7.8% (NS) at rest and 100 W, respectively]. The CaO2 was lower in A than in B because of the reduction in [Hb]. Thus also QaO2 was lower in A than in B (-32.0% and -11.9% at rest and at 100 W, respectively). The present results would suggest a down-regulation of the O2 transport system after bed rest.

1. Endurance athletes (E) undergo a marked reduction of arterial O2 saturation (Sa,O2) at maximal exercise in normoxia, which disappears when they breathe hyperoxic mixtures. In addition, at a given level of hypoxia, the drop in maximal O2 consumption (VO2,max) is positively related to the individual normoxic VO2,max. 2. These data suggest that the curve relating VO2,max to PI,O2 may be steeper and perhaps less curved in E than in sedentary subjects (S) with low VO2,max values because of the greater hypoxaemia in the latter, whence the hypotheses that (i) the relationship between VO2,max and PI,O2 may be set by the shape of the oxygen equilibrium curve; and (ii) the differences between E and S may be due to the different position on the oxygen equilibrium curve on which these subjects operate. These hypotheses have been tested by performing a systematic comparison of the VO2,max or Sa,O2 vs. PI,O2 relationships in E and S. 3. On ten subjects (five S and five E), VO2,max was measured by standard procedure during cycloergometric exercise. Sa,O2 was measured by finger-tip infrared oximetry. Arterialized blood PO2 (Pa,O2) and PCO2 (Pa,CO2) were determined in 80 microliters blood samples from an ear lobe. The subjects breathed ambient air or a N2-O2 mixture with an inspired O2 fraction (FI,O2) of 0.30, 0.18, 0.16, 0.13 and 0.11, respectively, VO2,max was normalized with respect to that obtained at the highest FI,O2. 4. The relationships between Sa,O2 or normalized VO2,max and FI,O2 (or PI,O2) had similar shapes, the data for E being systematically below and significantly different from those for S. Linear relationships between Sa,O2 and normalized VO2,max, statistically equal between E and S, were found. 5. We conclude that the relationships between either VO2,max or Sa,O2 and FI,O2 (or Pa,O2) may indeed be the mirror images of one another, implying a strict link between the decrease of VO2,max in hypoxia and the shape of the oxygen equilibrium curve, as hypothesized.

During the reambulation procedure after 35-day head-down tilt bed rest (HDTBR) for 9 men, we recorded for the first time heart rate (HR; with electrocardiogram) and arterial pressure profiles (fingertip plethysmography) for 5 min in HDTBR and horizontal (SUP) positions, followed by 12 min in standing position, during which 4 subjects fainted (intolerant, INT) and were laid horizontal again (Recovery). We computed: mean arterial pressure (P¯; pressure profiles integral mean), stroke volume (SV; obtained with Modelflow method), and cardiac output (Q̇; SV × HR). All cardiovascular data remained stable in HDTBR and SUP for both groups (EXP). Taking the upright posture, EXP showed a decrease in SV and an increase in HR, becoming significantly different from SUP within 1 min. Further evolution of these parameters kept Q̇ stable in both groups until the second minute of standing. Afterward, in INT, P̄ precipitated without further HR increases: SV stopped being corrected and Q̇ reached 2.9 ± 0.4 L·min−1 at the last 15 s of standing. Sudden drop in P̄ allowed identification of a low-pressure threshold in INT (70.7 ± 12.9 mm Hg), after which syncope occurred within 80 s. During Recovery, baroreflex curves showed a flat phase (P̄ increase, HR stable), followed by a steep phase (P̄ increased, HR decreased, starting when P̄ was 84.5 ± 12.5 mm Hg and Q̇ was 9.6 ± 1.5 L·min−1). INT, in contrast with tolerant subjects, did not sustain standing because HR was unable to correct for the P̄ drop. These results indicate a major role for impaired arterial baroreflexes in the onset of orthostatic intolerance.

The response of the O2 transport system to acute changes in alveolar ventilation (VA) was analysed. The fractional limitations to maximal O2 consumption (VO2max) imposed by the lungs (ventilation, FV, and lung-blood transfer, FL), the cardiovascular system (FQ), and peripheral O2 diffusion (Fp) were calculated according to a multifactorial model. A reference set of data, describing the status of O2 transport at maximal exercise in normoxia was used. The effects of VA on VO2max were assessed on the assumption of a constant reference O2 flow in mixed venous blood (QVO2). The changes in reference data after given independent changes in VA were calculated by an iterative procedure, until the VO2max value compatible with the constant reference QVO2 was found, at PIO2 values of 150 (normoxia), 130, 110 and 90 Torr. The VO2max changes in normoxia were less than expected assuming a linear O2 transport system, because of the flatness of the O2 dissociation curve around normoxic PO2. This affected the cardiovascular resistance to O2 flow, and its changes counterbalanced the effects on VO2max of induced changes in VA. This phenomenon was reversed in hypoxia, as the steep part of the O2 dissociation curve was approached. The fractional limitations to VO2max in normoxia resulted as follows: FV and FL provided between 5 and 12%, FQ between 59 and 78%, and Fp between 13 and 19% of the overall VO2max limitation. In hypoxia, FV and FL increased and FQ decreased. At PIO2 = 90 Torr, when VA was halved, FV, FL, FQ and Fp amounted to 0.35, 0.31, 0.20 and 0.14, respectively.

Achievements in breath-hold diving depend, amongst others, on body oxygen stores at start of dive. A diver with very high lung volumes could increase dive’s duration, and attain deeper depths for a given speed. Thus, we hypothesized that extreme breath-hold divers have very high lung volumes. On eight extreme breathhold divers (age 35 + 4 years, height 179 + 7 cm, body mass 76 + 6 kg) and 9 non-diving controls (age 37 + 6 years, height 177 + 4 cm, body mass 81 + 9 kg) residual volume, vital capacity and total lung capacity (TLC) were measured with a body plethysmograph. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured with a spirometer. Peak expiratory flow and flow-volume loops were measured with a pneumotachograph. In divers, but not in controls, volumes and capacities were systematically and significantly (p

To define the dynamics of cardiovascular adjustments to apnoea during immersion, beat-to-beat heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressures were recorded in six divers during and after prolonged apnoeas while resting fully immersed in 27 degrees C water. Apnoeas lasted 215 +/- 35 s. Compared to control values, HR decreased by 20 beats min(-1) and SBP and DBP increased by 23 and 17 mmHg, respectively, in the initial 20 +/- 3 s (phase I). Both HR and BP remained stable during the following 92 +/- 15 s (phase II). Subsequently, during the final 103 +/- 29 s, SBP and DBP increased linearly to values about 60% higher than control, whereas HR remained unchanged (phase III). Cardiac output (Q') decreased by 35% in phase I and did not further change in phases II and III. Compared to control, total peripheral resistances were twice and three times higher than control, respectively, at the end of phases I and III. After resumption of breathing, HR and BP returned to control values in 5 and 30 s, respectively. The time courses of cardiovascular adjustments to immersed breath-holding indicated that cardiac response took place only at the beginning of apnoea. In contrast, vascular responses showed two distinct adjustments. This pattern suggests that the chronotropic control via the baroreflex is modified during apnoea. These cardiovascular changes during immersed static apnoea are in agreement with those already reported for static dry apnoeas.

Sanchis-Gomar et al. (2009) performed an interesting experiment on rats, who had received 500 IU of rHuEPO-alpha three times a week for 2 weeks. These rats were then divided into two groups: one group was exposed intermittently to hypoxia (equivalent altitude of 4,000 m, 12 h per day), the other was not. The rats of the former group had variations of haematological parameters that are coherent with the concept of altitude acclimatization. This includes, of course, an increase in endogenous EPO, so that the erythropoietic stimulation index was altered. So, the authors conclude, intermittent hypoxic treatment after rHuEPO-alpha administration can signiWcantly modify the main haematological parameters tested by the anti-doping authorities. Consequently, Lippi and Franchini argue in their letter that intermittent hypoxic training should be banned as a doping procedure. They seem to overlook the fact that rats were exposed to an equivalent altitude of 4,000 m, which is not exactly the altitude were athletes use to go, but this is not a main point: some athletes could well spend 12 h per day (over night, for instance) in a hypobaric chambers at that altitude. The main point, since we deal with doping, is the following. According to the World Anti-Doping Code (available at http://www.wada-ama.org) of the World AntiDoping Agency (WADA), a substance or a method is recognised as doping when it meets, or it is a demonstrated masking agent of a substance that meets, at least two of these conditions: (1) it improves performance, (2) it carries along health risks, (3) it is contrary to what the International Olympic Committee calls “the spirit of sport”. Intermittent hypoxia exposure does not improve performance per se, is not harmful to health, is not contrary to the spirit of sport more than altitude acclimatization. So the argument of Luzzi and Franchini must rely on the concept that intermittent hypoxia is a masking agent (of rhEPO) of exogenous EPO administration at anti-doping control. But is it really a masking agent? Exogenous EPO can be identiWed directly in urine and in blood with electrophoresis, since the electric charge of the rhEpo molecule is less negative than that of endogenous Epo (Wide et al. 1995). The method underwent extensive validation, has been Wnely tuned, is highly reliable nowadays, and has been formally recognised by WADA in 2003. Intermittent hypoxia exposure does not conceal rhEPO from detection by electrophoresis. Thus, it cannot be considered, to my mind, a masking agent. In conclusion, none of the conditions established by WADA for the inclusion of a substance or a method in the doping list is fulWlled by intermittent hypoxia exposure. So, I kindly disagree with the proposal by Luzzi and Franchini of banning intermittent hypoxia exposure as a doping procedure.

Submaximal and/or peak levels of oxygen consumption (VO2), pulmonary ventilation (VE), heart rate (HR), stroke volume of heart (SV), cardiac output (Q), muscle blood flow (qm), as well as the kinetics of readjustment of gas exchange, Q and qm (t1/2 VO2on-, t1/2 Qon-, t1/2 qmon-) were determined in 44 heart transplant recipients (HTRs) and in a group of age-, sex-, and physical activity-matched control subjects (CTL) when carrying out rectangular loads (25 to 125 W) on a bicycle ergometer. The increase of SV occurring at work onset appears to compensate in HTRs for the sluggish readjustment of HR so that the rate of readjustment of Q is kept within normal limits. As a consequence, qm, t1/2 q mon-, and t1/2 VO2on- appear to be similar or only moderately delayed in HTRs compared with CTLs. It is concluded that in HTRs, because of constrained maximum HR, only work loads up to 60% of the VO2max of CTLs may be attained; also, owing to the fast readjustment of Q, up to work loads of 75 to 100 W, the rest to work transition phase is not impaired.

The maximal instantaneous muscle power (wi,max) probably reflects the maximal rate of adenosine 5'-triphosphate (ATP) hydrolysis (ATPmax), a temperature-dependent variable, which gives rise to the hypothesis that temperature, by affecting ATPmax, may also influence wi,max. This hypothesis was tested on six subjects, whose vastus lateralis muscle temperature (Tmuscle) was monitored by a thermocouple inserted approximately 3 cm below the skin surface. The Wi,max was determined during a series of high jumps off both feet on a force platform before and after immersion up to the abdomen for 90 min in a temperature controlled (T = 20 +/- 0.1 degrees C) water bath. Control Tmuscle was 35.8 +/- 0.7 degrees C, with control Wi,max being 51.6 (SD 8.7) W.kg-1. After cold exposure, Tmuscle decreased by about 8 degrees C, whereas wi,max 27% lower. The temperature dependence of Wi,max was found to be less (Q10 less than 1.5, where Q10 is the temperature coefficient as calculated in other studies) than reported in the literature for ATPmax. Such a low Q10 may reflect an increase in the mechanical equivalent of ATP splitting, as a consequence of the reduced velocity of muscle contraction occurring at low Tmuscle.

Maximal O(2) consumption (V(O)(2) max) is an index of integrated cardiopulmonary function. After having defined it, discussed its limitation, and described its measurement, we present data during and after space flight and simulation. During gravity withdrawal, V(O)(2) max stays unchanged. It suddenly drops when the subject is exposed to gravity again and V(O)(2) max is measured upright. Its decrease has a rapid component, attributed to cardiovascular "deconditioning", and a slower component, related to muscle hypotrophy. The cardiovascular adaptation to microgravity and the modalities whereby, upon gravity resumption, it leads to V(O)(2) max drop are discussed. When gravity is resumed, the cardiovascular system does not provide an adequate response to upright exercise, because it is regulated differently from before microgravity exposure. The approach to countermeasures during space flight should change accordingly. Most important becomes ensuring the minimum impact of gravity resumption on the cardiovascular system rather than sustaining V(O)(2) max through aerobic exercise training. Countermeasures centred on gravity application during space flight should be given priority.

BACKGROUND: Physical inactivity represents a major risk for cardiovascular disorders, such as hypertension, myocardial infarction or sudden death; however, underlying mechanisms are not clearly elucidated. Clinical and epidemiological investigations suggest, beyond molecular changes, the possibility of an induced impairment in autonomic cardiovascular regulation. However, this hypothesis has not been tested directly. METHODS: Accordingly, we planned a study with noninvasive, minimally intrusive, techniques on healthy volunteers. Participants were maintained for 90 days strictly in bed, 24 h a day, in head-down (-6 degrees ) position (HDBR). Physical activity was thus virtually abolished for the entire period of HDBR. We examined efferent muscle sympathetic nerve activity, as a measure of vascular sympathetic control, baroreceptor reflex sensitivity, heart rate variability (assessing cardiovagal regulation), RR and systolic arterial pressure and low-frequency and high-frequency normalized components (as a window on central oscillatory regulation). Measures were obtained at rest and during simple maneuvers (moderate handgrip, lower body negative pressure and active standing) to assess potential changes in autonomic cardiovascular responsiveness to standard stimuli and the related oscillatory profiles. RESULTS: HDBR transiently reduced muscle sympathetic nerve activity, RR, heart rate variability and baroreceptor reflex sensitivity late during HDBR or early during the recovery phase. Conversely, oscillatory profiles of RR and systolic arterial pressure variability were maintained throughout. Responsiveness to test stimuli was also largely maintained. CONCLUSION: Prolonged inactivity as induced by HDBR in healthy volunteers reduces both cardiovagal and vascular sympathetic regulation, while largely maintaining peripheral responsiveness to standardized stimuli and sparing the functional structure of central oscillatory cardiovascular regulation.

End tidal O2 and CO2 (PETCO2) pressures, expired volume, blood lactate concentration ([Lab]), and arterial blood O2 saturation [dry breath holds (BHs) only] were assessed in three elite breath-hold divers (ED) before and after deep dives and BH and in nine control subjects (C; BH only). After the dives (depth 40-70 m, duration 88-151 s), end-tidal O2 pressure decreased from approximately 140 Torr to a minimum of 30.6 Torr, PETCO2 increased from approximately 25 Torr to a maximum of 47.0 Torr, and expired volume (BTPS) ranged from 1.32 to 2.86 liters. Pulmonary O2 exchange was 455-1,006 ml. CO2 output approached zero. [Lab] increased from approximately 1.2 mM to at most 6.46 mM. Estimated power output during dives was 513-929 ml O2/min, i.e. approximately 20-30% of maximal O2 consumption. During BH, alveolar PO2 decreased from approximately 130 to less than 30 Torr in ED and from 125 to 45 Torr in C. PETCO2 increased from approximately 30 to approximately 50 Torr in both ED and C. Contrary to C, pulmonary O2 exchange in ED was less than resting O2 consumption, whereas CO2 output approached zero in both groups. [Lab] was unchanged. Arterial blood O2 saturation decreased more in ED than in C. ED are characterized by increased anaerobic metabolism likely due to the existence of a diving reflex.