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After a short historical account, and a discussion of Hill and Meyerhof’s theory of the energetics of muscular exercise, we analyse steady-state rest and exercise as the condition wherein coupling of respiration to metabolism is most perfect. The quantitative relationships show that the homeostatic equilibrium, centred around arterial pH of 7.4 and arterial carbon dioxide partial pressure of 40 mmHg, is attained when the ratio of alveolar ventilation to carbon dioxide flow ($${\dot{V}}_{A}/{\dot{V}}_{R}{CO}_{2}$$ V ˙ A / V ˙ R CO 2 ) is − 21.6. Several combinations, exploited during exercise, of pertinent respiratory variables are compatible with this equilibrium, allowing adjustment of oxygen flow to oxygen demand without its alteration. During exercise transients, the balance is broken, but the coupling of respiration to metabolism is preserved when, as during moderate exercise, the respiratory system responds faster than the metabolic pathways. At higher exercise intensities, early blood lactate accumulation suggests that the coupling of respiration to metabolism is transiently broken, to be re-established when, at steady state, blood lactate stabilizes at higher levels than resting. In the severe exercise domain, coupling cannot be re-established, so that anaerobic lactic metabolism also contributes to sustain energy demand, lactate concentration goes up and arterial pH falls continuously. The $${\dot{V}}_{A}/{\dot{V}}_{R}{CO}_{2}$$ V ˙ A / V ˙ R CO 2 decreases below − 21.6, because of ensuing hyperventilation, while lactate keeps being accumulated, so that exercise is rapidly interrupted. The most extreme rupture of the homeostatic equilibrium occurs during breath-holding, because oxygen flow from ambient air to mitochondria is interrupted. No coupling at all is possible between respiration and metabolism in this case.

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.

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.

Purpose We hypothesised that, during a light-to-moderate exercise transient, compared to an equivalent rest-to-exercise transient, (1) a further baroreflex sensitivity (BRS) decrease would be slower, (2) no rapid heart rate (HR) response would occur, and (3) the rapid cardiac output (CO) response would have a smaller amplitude (A1). Hence, we analysed the dynamics of arterial baroreflexes and the HR and CO kinetics during rest-to-50 W (0–50 W) and 50-to-100 W (50–100 W) exercise transients. Methods 10 subjects performed three 0–50 W and three 50–100 W on a cycle ergometer. We recorded arterial blood pressure profiles (photo-plethysmography) and R-to-R interval (RRi, electrocardiography). The former were analysed to obtain beat-by-beat mean arterial pressure (MAP) and stroke volume (SV). CO was calculated as SV times HR. BRS was measured by modified sequence method. Results During 0–50 W, MAP transiently fell (− 9.0 ± 5.7 mmHg, p −1 at 50 W (p −1, p −1 at 100 W (p −1, p = 0.07 vs. 50 W). A1 for HR was 9.2 ± 6.0 and 6.0 ± 4.5 min−1 in 0–50 W and 50–100 W, respectively (p = 0.19). The corresponding A1 for CO were 2.80 ± 1.54 and 0.91 ± 0.55 l∙min−1 (p Conclusion During 50–100 W, with respect to 0–50 W, BRS decreased more slowly, in absence of a prompt pressure decrease. BRS decrease and rapid HR response in 50–100 W were unexpected and ascribed to possible persistence of some vagal tone at 50 W.

Water immersion adds additional drag and metabolic demand for limb movement with respect to air, but its effect on the internal metabolic power (Ėint) of cycling is unknown. We aimed at quantifying the increase in Ėint during underwater cycling with respect to dry conditions at different pedaling rates.Twelve healthy subjects (four women) pedaled on a waterproof cycle ergometer in an experimental pool that was either empty (DRY) or filled with tap water at 30.8°C ± 0.6°C (WET). Four different pedal cadences (fp) were studied (40, 50, 60, and 70 rpm) at 25, 50, 75, and 100 W. The metabolic power at steady state was measured via open circuit respirometry, and Ėint was calculated as the metabolic power extrapolated for 0 W.The Ėint was significantly higher in WET than in DRY at 50, 60, and 70 rpm (81 ± 31 vs 32 ± 30 W, 167 ± 35 vs 50 ± 29 W, 311 ± 51 vs 81 ± 30 W, respectively, all P0.0001), but not at 40 rpm (16 ± 5 vs 11 ± 17 W, P0.99). Ėint increased with the third power of fp both in WET and DRY (R2 = 0.49 and 0.91, respectively).Water drag increased Ėint, although limbs unloading via the Archimedes' principle and limbs shape could be potential confounding factors. A simple formula was developed to predict the increase in mechanical power in dry conditions needed to match the rate of energy expenditure during underwater cycling: 44 fp3 - 7 W, where fp is expressed in Hertz.

The power–duration relationship has been variously modelled, although duration must be acknowledged as the dependent variable and is supposed to represent the only source of experimental error. However, there are certain situations, namely extremely high power outputs or outdoor field conditions, in which the error in power output measurement may not remain negligible. The geometric mean (GM) regression method deals with the assumption that also the independent variable is subject to a certain amount of experimental error, but has never been utilized in this context. We applied the GM regression method for the two- and three-parameter critical power models and tested it against the usual weighted least square (WLS) procedure with our previous published data. There were no significant differences between parameter estimates of WLS and GM. Bias and limit of agreements between the two methods were low, while correlation coefficients were high (0.85–1.00). GM provided equivalent results with respect to WLS in fitting the critical power model to experimental data and for its conceptual characteristics must be preferred wherever concerns on the precision of P measurement are present, such as for in-field power meters.

This article discusses the limits of deep breath-hold diving in humans. After a short historical introduction and a discussion of the evolution of depth records, the classical theories of breath-hold diving limits are presented and discussed, namely that of the ratio between total lung capacity and residual volume and that of blood shift, implying an increase in central blood volume. Then the current vision is introduced, based on the principles of the energetics of muscular exercise. The new vision has turned the classical vision upside down, moving the discussion to a different level. A direct consequence of the new theory is the importance of having large lung volumes at the start of a dive, in order to increase body oxygen stores. I finally discuss the role of anaerobic lactic metabolism as a possible mechanism of oxygen preservation, thus prolonging breath-hold duration.

This article starts from an aeronautical tragedy to track briefly the history of the oxygen equilibrium curve and the creation of Hill’s model of it. After having argued that the characteristics of such a curve determine the non-linear behaviour of the respiratory system, I discussed some functional consequences of this behaviour, which explain how it happened that Reinhold Messner succeeded in the extraordinary enterprise of climbing Mount Everest without supplementary oxygen.

Purpose: The three-parameter model of critical power (3-p) implies that in the severe exercise intensity domain time to exhaustion (Tlim) decreases hyperbolically with power output starting from the power asymptote (critical power, ẇcr) and reaching 0 s at a finite power limit (ẇ0) thanks to a negative time asymptote (k). We aimed to validate 3-p for short Tlim and to test the hypothesis that ẇ0 represents the maximal instantaneous muscular power.Methods: Ten subjects performed an incremental test and nine constant-power trials to exhaustion on an electronically braked cycle ergometer. All trials were fitted to 3-p by means of non-linear regression, and those with Tlim greater than 2 min also to the 2-parameter model (2-p), obtained constraining k to 0 s. Five vertical squat jumps on a force platform were also performed to determine the single-leg (i.e., halved) maximal instantaneous power.Results: Tlim ranged from 26 ± 4 s to 15.7 ± 4.9 min. In 3-p, with respect to 2-p, ẇcr was identical (177 ± 26 W), while curvature constant W' was higher (17.0 ± 4.3 vs 15.9 ± 4.2 kJ, p < 0.01). 3-p-derived ẇ0 was lower than single-leg maximal instantaneous power (1184 ± 265 vs 1554 ± 235 W, p < 0.01).Conclusions: 3-p is a good descriptor of the work capacity above ẇcr up to Tlim as short as 20 s. However, since there is a discrepancy between estimated ẇ0 and measured maximal instantaneous power, a modification of the model has been proposed.

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.

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.

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.

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.

This article reviews the concept of maximal oxygen consumption ( $$\dot{V}\hbox{O}_{2\text{max} }$$ V ˙ O 2 max ) from the perspective of multifactorial models of $$\dot{V}\hbox{O}_{2\text{max} }$$ V ˙ O 2 max limitation. First, I discuss procedural aspects of $$\dot{V}\hbox{O}_{2\text{max} }$$ V ˙ O 2 max measurement: the implications of ramp protocols are analysed within the theoretical work of Morton. Then I analyse the descriptive physiology of $$\dot{V}\hbox{O}_{2\text{max} }$$ V ˙ O 2 max , evidencing the path that led to the view of monofactorial cardiovascular or muscular $$\dot{V}\hbox{O}_{2\text{max} }$$ V ˙ O 2 max limitation. Multifactorial models, generated by the theoretical work of di Prampero and Wagner around the oxygen conductance equation, represented a radical change of perspective. These models are presented in detail and criticized with respect to the ensuing experimental work. A synthesis between them is proposed, demonstrating how much these models coincide and converge on the same conclusions. Finally, I discuss the cases of hypoxia and bed rest, the former as an example of the pervasive effects of the shape of the oxygen equilibrium curve, the latter as a neat example of adaptive changes concerning the entire respiratory system. The conclusion is that the concept of cardiovascular $$\dot{V}\hbox{O}_{2\text{max} }$$ V ˙ O 2 max limitation is reinforced by multifactorial models, since cardiovascular oxygen transport provides most of the $$\dot{V}\hbox{O}_{2\text{max} }$$ V ˙ O 2 max limitation, at least in normoxia. However, the same models show that the role of peripheral resistances is significant and cannot be neglected. The role of peripheral factors is greater the smaller is the active muscle mass. In hypoxia, the intervention of lung resistances as limiting factors restricts the role played by cardiovascular and peripheral factors.

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.

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 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.

This chapter contains an analysis of the steady-state concept, as it is applied during light exercise. In this case, oxygen consumption increases upon exercise onset to attain a steady level, which can be maintained for a long period of time. The steady-state oxygen consumption is proportional to the exerted mechanical power. Under these circumstances, there is neither accumulation of lactate in blood nor changes in muscle phosphocreatine concentration: aerobic metabolism sustains the entire energy requirement of the exercising body. Once the steady state has been attained, the flow of oxygen is the same at all levels along the respiratory system. The quantitative relations determining the flow of oxygen across the alveoli and in blood are discussed. Special attention is given to the effects of ventilation—perfusion inequality and to the diffusion—perfusion interaction equations. The cardiovascular responses at exercise steady state are analysed in the context of the equilibrium between systemic oxygen delivery and systemic oxygen return. The relationship between oxygen consumption and power is discussed, along with the distinction between external and internal work during cycling. The concepts of mechanical efficiency of exercise and energy cost of locomotion are analysed. Concerning the latter, the distinction between aerodynamic work and frictional work is introduced. The roles of the cross-sectional surface area on the frontal plane and of air density in aerodynamic work are discussed. To end with, an equation linking ventilation, circulation and metabolism at exercise in a tight manner is developed, around the notion that the homeostasis of the respiratory system at exercise is maintained around given values of the constant oxygen return. This equation tells that, as long as we are during steady-state exercise in normoxia, any increase in the exercise metabolic rate requires an increase in ventilation that is proportional to that in oxygen consumption only if the pulmonary respiratory quotient stays invariant does not change, and an increase in cardiac output that is not proportional to the corresponding increase in oxygen consumption. At intense exercise, when lactate accumulation also occurs and hyperventilation superimposes, a new steady state would be attained only at \( P_{A}{\text{CO}}_{2} \) values lower than 40 mmHg: the homeostasis of the respiratory system would be modified. This new steady state, however, is never attained in fact, for reasons that are discussed in Chap. 3.

This chapter contains a short summary of the historical developments that led to the contemporary vision of the energetics of muscular exercise, from the perspective of the School of Milano created by Rodolfo Margaria. Special attention is given to the history of respiratory gases and to the biochemical developments that led to the conception of intermediate metabolism (glycolysis, Krebs cycle, oxidative phosphorylation) and of the Lohmann’s reaction. The developments that led to the cross-bridge theory of muscular contraction are mentioned. The development of the concept of respiratory system and the creation of the oxygen equilibrium curve are also treated. The historical developments concerning key concepts such as maximal oxygen consumption and oxygen deficit are presented. The confutation of Hill and Meyerhof theory of exercise energetics by Margaria is discussed. This confutation led to the formulation of the general equation of the energetics of muscular exercise. The general equation was analytically discussed by di Prampero in 1981. That review was the last systematic overview of the energetics of muscular exercise. Several important reviews came afterwards, but only on specific, selected aspects of the energetics of muscular exercise (e.g. maximal oxygen consumption or exercise transients). This book has the ambition of bridging the temporal gap between di Prampero’s review and current knowledge. It is an attempt at providing a critical answer to the following question: How did the general theory of the energetics of muscular exercise resist 30 years of further developments? What could be accommodated into it, what was a challenge to it? Under which respects was it consolidated, and under which respects was it falsified, by the continuously growing knowledge in the field? Answering these questions is a complex, perhaps somewhat presumptuous task, which requires revisiting the concepts discussed by di Prampero in 1981 in the perspective of nowadays knowledge, and introducing and discussing some new concepts, which had been meanwhile created, in the context of the general theory.

As soon as the concept of maximal oxygen consumption \( (\dot{V}\,{\text{O}}_{{2{ \max }}} ) \) was created, it was clear that \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) was limited somewhere along the respiratory system. The quest for the single factor limiting \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) went on for long, with highly contradictory outcomes. The way of looking at \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) limitation, however, changed drastically some 30 years ago. The resumption of the oxygen cascade theory as a tool for a holistic description of the respiratory system led to the development of multifactorial models of \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) limitation. Two such models are currently available, one created by Pietro Enrico di Prampero and the other by Peter Wagner. These models are described in detail and criticized. The evidence supporting the predictions generated by the two models is presented. Demonstration is provided that the two models converge indeed on the same conclusion, namely that most of the limitation to \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) in normoxia is provided by cardiovascular oxygen transport. However, the same models show that the role of peripheral oxygen diffusion and utilization as limiting factors is such that it cannot be neglected. The special case of \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) in hypoxia is then presented, and the effects of a nonlinear oxygen equilibrium curve are discussed. It is acknowledged that as long as we operate on the flat portion of the oxygen equilibrium curve, the lungs do not limit \( \dot{V}\,{\text{O}}_{{2{ \max }}} \), but as soon as the steep part of the curve is attained, the lungs take over a significant fraction of \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) limitation. Finally, the case of prolonged bed rest is discussed as an example of \( \dot{V}\,{\text{O}}_{{2{ \max }}} \) changes induced by simultaneous multiple modifications occurring at various levels along the respiratory system.

The aim of this study was to evaluate the usefulness of technetium-99m sestamibi scintimammography (SSM) and combined use of SSM and X-ray mammography (MG) in premenopausal patients with small (≤2 cm) suspicious breast lesions. Eighty-seven premenopausal women (median age 47 years, range 32–52) with breast lesions ranging from 4 to 20 mm in greatest diameter (median 12 mm) and detected by MG, underwent SSM prior to open breast biopsy. A planar camera and single-photon emission tomography (SPET) technique were used in 23 (26.4%) and 64 (73.6%) patients, respectively. At histological examination, 72 (82.8%) breast cancers (pT1a=3, pT1b=27, pT1c=42) and 15 (17.2%) benign masses were found. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MG and SSM were 80.6% vs 80.6%, 60.0% vs 93.3% (P

A model of the metabolic internal power (Eint) during cycling, which includes the gravity acceleration (ag) as a variable, is presented. This model predicts that Eint is minimal in microgravity (0 g; g=9. 81 m s-2), and increases linearly with ag, whence the hypothesis that the oxygen uptake (VO2) during cycling depends on ag. Repeated VO2 measurements during steady-state exercise at 50, 75 and 100 W on the cycle ergometer, performed in space (0 g) and on Earth (1 g) on two subjects, validated the model. VO2 was determined from the time course of decreasing O2 fraction during rebreathing. The gas volume during rebreathing was determined by the dilution principle, using an insoluble inert gas (SF6). Average VO2 for subject 1 at each power was 0.99, 1.21 and 1.52 L min-1 at 1 g (n=3) and 0.91, 1.13 and 1.32 L min-1 at 0 g (n=5). For subject 2 it was 0.90, 1.12 and 1. 42 L min-1 at 1 g, and 0.76, 0.98 and 1.21 L min-1 at 0 g. These values corresponded to those predicted from the model. Although resting VO2 was lower at 0 g than at 1 g, the net (total minus resting) exercise VO2 was still smaller at 0 g than at 1 g. This difference reflects the lower Eint at 0 g.

The following is the abstract of the article discussed in the subsequent letter: Koga, Shunsaku, Tomoyuki Shiojiri, Narihiko Kondo, and Thomas J. Barstow. Effect of increased muscle temperature on oxygen uptake kinetics during exercise. J. Appl. Physiol. 83(4): 1333–1338, 1997.—To test whether increased muscle temperature (Tm) would improve O2 uptake (V˙o 2) kinetics, seven men performed transitions from rest to a moderate work rate [below the estimated lactate threshold (LTest)] and a heavy work rate (V˙o 2 = 50% of the difference between LTest and peakV˙o 2) under conditions of normal Tm (N) and increased Tm (H), produced by wearing hot water-perfused pants before exercise. Quadriceps Tm was significantly higher in H, but rectal temperature was similar for the two conditions. There were no significant differences in the amplitudes of the fast component ofV˙o 2 or in the time constants of the on and off transients for moderate and heavy exercise between the two conditions. The increment inV˙o 2 between the 3rd and 6th min of heavy exercise was slightly but significantly smaller for H than for N. These data suggest that elevated Tm before exercise onset, which would have been expected to increase O2delivery and off-loading to the muscle, had no appreciable effect on the fast exponential component ofV˙o 2 kinetics (invariant time constant). These data further suggest that elevated Tm does not contribute to the slow component ofV˙o 2 during heavy exercise.

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.

Morton (J Sport Sci 29:307–309, 2011) proposed a model of the peak power attained in ramp protocol ( $$\dot{w}_{\text{peak}}$$ ) that included critical power (CP) and anaerobic capacity as constants, and mean ramp slope (S) as variable. Our hypothesis is that $$\dot{w}_{\text{peak}}$$ depends only on S, so that Morton’s model should be applicable in all types of ramps. The aim of this study was to test this hypothesis by validating Morton’s model using stepwise ramp tests with invariant step increment and increasing step duration. Sixteen men performed six ramp tests with 25 W increments. Step duration was: 15, 30, 60, 90, 120 and 180 s. Maximal oxygen consumption ( $$\dot{V}{\text{O}}_{{ 2 {\text{max}}}}$$ ) and $$\dot{w}_{\text{peak}}$$ were identified as the highest values reached during each test. An Astrand-type test was also performed. We measured oxygen consumption and ventilatory variables, together with lactate and heart rate. $$\dot{V}{\text{O}}_{2\hbox{max} }$$ was the same in all tests; $$\dot{w}_{\text{peak}}$$ was significantly lower the longer the step duration, and all values differed from the maximal power of the Astrand-type test ( $$\dot{w}_{\hbox{max} }$$ ). Morton’s model yielded an excellent fitting, with mean CP equal to 198.08 ± 37.46 W and anaerobic capacity equal to 16.82 ± 5.69 kJ. Morton’s model is a good descriptor of the mechanics of ramp tests. Further developments of Morton’s model demonstrated that, whereas $$\dot{w}_{\text{peak}}$$ is a protocol-dependent variable, the difference between $$\dot{w}_{\hbox{max} }$$ and CP is a constant, so that their values do not depend on the protocol applied.