Search

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 (<2 s) tilted from supine (S) to upright (U) and vice versa every 3 min, at rest and during steady-state 50 W pedaling. Mean arterial pressure (MAP) was measured by finger cuff (Portapres) and R-to-R interval (RRi) by electrocardiography. BRS was computed with the sequence method both during steady and unsteady states. At rest, BRS was 35.1 ms·mmHg-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. [ABSTRACT FROM AUTHOR]

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 ( 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. [ABSTRACT FROM AUTHOR]

Regular physical exercise enhances memory functions, synaptic plasticity in the hippocampus, and brain derived neurotrophic factor (BDNF) levels. Likewise, short periods of exercise, or acute exercise, benefit hippocampal plasticity in rodents, via increased endocannabinoids (especially anandamide, AEA) and BDNF release. Yet, it remains unknown whether acute exercise has similar effects on BDNF and AEA levels in humans, with parallel influences on memory performance. Here we combined blood biomarkers, behavioral, and fMRI measurements to assess the impact of a single session of physical exercise on associative memory and underlying neurophysiological mechanisms in healthy male volunteers. 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. Memory after moderate intensity exercise correlated with exercise-induced increases in both AEA and BNDF levels: while AEA was associated with hippocampal activity during memory recall, BDNF enhanced hippocampal memory representations and long-term performance. These findings demonstrate that acute moderate intensity exercise benefits consolidation of hippocampal memory representations, and that endocannabinoids and BNDF signaling may contribute to the synergic modulation of underlying neural plasticity mechanisms. [ABSTRACT FROM AUTHOR]

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 <± 0.4 l for both). Test-retest reliability was high (intraclass correlation coefficient >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. [ABSTRACT FROM AUTHOR]

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 < 0.05). At exercise, BRS in φ1 was 6.4 [3.9-13.1] in air and 6.7 [4.1-9.5] in O2. 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. [ABSTRACT FROM AUTHOR]

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. 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 (PIO2and PAO2, respectively) and CO2 (PICO2 and PACO2, respectively) and the steady‐state values of the pre‐BH respiratory exchange ratio (RER). In pure oxygen, the model respected the constraint of PACO2=−PAO2+PIO2. 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, PAO2 and PACO2 before and at the end of all BHs. Measured data were fitted through the model. In air, PIO2 = 150 ± 1 mmHg and PICO2 = 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; PAO2 = 107 ± 7 mmHg at rest and 102 ± 8 mmHg at 30 W; and PACO2 = 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 PIO2: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Blood pressure response to apnoea overlaps in air and in O 2. • In O 2 , apnoeas show a milder response in heart rate and peripheral resistances. • CO 2 rise may trigger the pressure increase in phase III. To check whether the evolution of alveolar pressures of O 2 (P A O 2) and CO 2 (P A CO 2) explains the cardiovascular responses to apnoea, eight divers performed resting apnoeas of increasing duration in air and in O 2. We measured heart rate (f H), arterial pressure (AP), and peripheral resistances (TPR) beat-by-beat, P A O 2 and P A CO 2 at the end of each apnoea. The three phases of the cardiovascular response to apnoea were observed. In O 2 , TPR increase (9 ± 4 mmHg min l−1) and f H 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, P A O 2 and P A CO 2 were 50 ± 9 and 48 ± 5 mmHg, respectively; corresponding values in O 2 were 653 ± 8 mmHg and 55 ± 5 mmHg. At end of phase II, P A O 2 and P A CO 2 in air were 90 ± 13 mmHg and 42 ± 4 mmHg respectively; corresponding values in O 2 were 669 ± 7 mmHg and 47 ± 6 mmHg. The P A CO 2 increase may trigger the AP rise in phase III. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ( f H ), stroke volume ( Q S ), and arterial oxygen saturation (SpO 2 ) 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 < 0.05). In air, no φ2 was observed. Conversely, in oxygen, a φ2 of 28 ± 5 s duration appeared, during which systolic BP (185 ± 29 mmHg), f H (93 ± 16 bpm) and Q S (91 ± 16 ml) remained stable. End-apnoea SpO 2 was 95.5 ± 1.9% in air and 100% in oxygen. The results support the tested hypothesis. [ABSTRACT FROM AUTHOR]

Introduction: We tested the linear critical power ([Formula: see text]) model for discrete incremental ramp exercise implying recovery intervals at the end of each step.Methods: Seven subjects performed incremental (power increment 25 W) stepwise ramps to subject's exhaustion, with recovery intervals at the end of each step. Ramps' slopes (S) were 0.83, 0.42, 0.28, 0.21, and 0.08 W s-1; recovery durations (t r) were 0 (continuous stepwise ramps), 60, and 180 s (discontinuous stepwise ramps). We determined the energy store component (W'), the peak power ([Formula: see text]), and [Formula: see text].Results: When t r = 0 s, [Formula: see text] and W' were 187 ± 26 W and 14.5 ± 5.8 kJ, respectively. When t r = 60 or 180 s, the model for ramp exercise provided inconsistent [Formula: see text] values. A more general model, implying a quadratic [Formula: see text] versus [Formula: see text] relationship, was developed. This model yielded, for t r = 60 s, [Formula: see text] = 189 ± 48 W and W' = 18.6 ± 17.8 kJ, and for t r = 180 s, [Formula: see text] = 190 ± 34 W, and W' = 16.4 ± 16.7 kJ. These [Formula: see text] and W' did not differ from the corresponding values for t r = 0 s. Nevertheless, the overall amount of energy sustaining work above [Formula: see text], due to energy store reconstitution during recovery intervals, was higher the longer t r, whence higher [Formula: see text] values.Conclusions: The linear [Formula: see text] model for ramp exercise represents a particular case (for t r = 0 s) of a more general model, accounting for energy resynthesis following oxygen deficit payment during recovery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The purpose was to compare the resting energy expenditure (REE) measured with the Q-NRG™+ metabolic-cart (MREE) with REE predicted by equations (the Harris-Benedict formula and an equation developed in ward, REE-HB and REE-W, respectively). We also aimed to assess the agreement of the measurements of oxygen consumption ( V ̇ O 2 ) and carbon dioxide production ( V ̇ CO 2 ) at different inspired fractions of oxygen (FiO 2). 27 mechanically ventilated ICU patients were enrolled. V ̇ O 2 and V ̇ CO 2 were measured by Q-NRG™+ during breathing 40% and 60% FiO 2. MREE was compared with REE-W and REE-HB normalized for body weight. V ̇ O 2 was 233.0 (95.2) ml/min and 217.5 (89.8) ml/min at FiO 2 40% and 60%, respectively (NS). V ̇ CO 2 was 199.0 (91.7) ml/min at FiO 2 40%, and 197.5 (85.5) ml/min at FiO 2 60% (NS). The REE estimated from the equations was significantly different from the MREE. The best agreement was found for the Harris-Benedict equation without correction for stress-factors. Harris-Benedict equation corrected overestimates REE. This new metabolic cart Q-NRG™+ provides a concordance of values for V ̇ O 2 and V ̇ CO 2 when measured at different FiO 2 , and is a reliable tool for estimating energy expenditure and assessing the nutritional needs of the patient. This study demonstrates that the estimation of REE using predictive formulas does not allow accurate calculation of metabolic demands in ventilated intensive care patient. However, predictive equations allow for a rapid assessment of REE and calculation of the amount of energy derived from different substrates. • A new metabolic-cart was used to evaluate V ̇ O 2 and V ̇ CO 2 at different FiO 2 in ICU. • This new tool allows the measurement of REE in mechanically ventilated patients. • REE measured by metabolic cart and predicted by formulas have been compared. • REE by formulas does not allow accurate calculation of metabolic demands. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose 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. Methods Nineteen divers performed maximal apnoeas in air and oxygen. We measured beat-by-beat arterial pressure, heart rate ( f H ), stroke volume (SV), cardiac output ( Q ˙ ). Results The f H , 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 ( p < 0.05), respectively. At end of apnoea, arterial oxygen saturation was 1.00 ± 0.00 in oxygen and 0.75 ± 0.10 in air. Conclusions The results support the tested hypothesis. Lack of hypoxaemia during oxygen apnoeas suggests that, if chemoreflexes determine ϕ3, the increase in CO 2 stores might play a central role in eliciting their activation. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies of cardiovascular responses in hypergravity suggest increased sympathetic regulation. The analysis of spontaneous heart rate variability (HRV) parameters and spontaneous baroreflex sensitivity (BRS) informs on the reciprocal balance of parasympathetic and sympathetic regulations at rest. This paper was aimed at determining the effects of gravitational acceleration ( a) on HRV and BRS. Methods: Eleven healthy subjects (age 26.6 ± 6.1) were studied in a human centrifuge at four a levels (1, 1.5, 2 and 2.5 g) during 5-min sessions at rest. We evaluated spontaneous variability of R-R interval (RR), and of systolic and diastolic blood pressure (SAP and DAP, respectively), by power spectral analysis, and BRS by the sequence method, using the BRSanalysis software. Results: At 2.5 g, compared to 1 g, (1) the total power ( P) and the powers of LF and HF components of HRV were lower, while the LF/HF ratio was higher; (2) normalized units for LF and HF did not changed significantly; (3) the P, LF and HF powers of SAP were higher; (4) the P and LF power of DAP were higher; and (5) BRS was decreased. Conclusions: These results do not agree with the notion of sympathetic up-regulation supported by the increase in HR and DAP (tonic indices), and of SAP and DAP LF powers (oscillatory indices). The P reduction leads to speculate that only the sympathetic branch of the ANS might have been active during elevated a exposure. The vascular response occurred in a condition of massive baroreceptive unloading. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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). Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Introduction: Interpolation methods circumvent poor time resolution of breath-by-breath oxygen uptake ( $$\dot{V}{\text{O}}_{2}$$ ) kinetics at exercise onset. We report an interpolation-free approach to the improvement of poor time resolution in the analysis of $$\dot{V}{\text{O}}_{2}$$ kinetics. Methods: Noiseless and noisy (10 % Gaussian noise) synthetic data were generated by Monte Carlo method from pre-selected parameters (Exact Parameters). Each data set comprised 10 ( $$\dot{V}{\text{O}}_{2}$$ )-on transitions with noisy breath distribution within a physiological range. Transitions were superposed (no interpolation, None), then analysed by bi-exponential model. Fitted model parameters were compared with those from interpolation methods (average transition after Linear or Step 1-s interpolations), applied on the same data. Experimental data during cycling were also analysed. The 95 % confidence interval around a line of parameters' equality was computed to analyse agreement between exact parameters and corresponding parameters of fitted functions. Results: The line of parameters' equality stayed within confidence intervals for noiseless synthetic parameters with None, unlike Step and Linear, indicating that None reproduced Exact Parameters. Noise addition reduced differences among pre-treatment procedures. Experimental data provided lower phase I time constants with None than with Step. Conclusion: In conclusion, None revealed better precision and accuracy than Step and Linear, especially when phenomena characterized by time constants of <30 s are to be analysed. Therefore, we endorse the utilization of None to improve the quality of breath-by-breath $$\dot{V}{\text{O}}_{2}$$ data during exercise transients, especially when a double exponential model is applied and phase I is accounted for. [ABSTRACT FROM AUTHOR]

Abstract: We hypothesised that phase II time constant (τ 2) of alveolar O2 uptake () is longer in hypoxia than in normoxia as a consequence of a parallel deceleration of the kinetics of O2 delivery (). To test this hypothesis, breath-by-breath and beat-by-beat 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 (). Blood lactate ([La]b) accumulation during the exercise transient was also measured. The τ 2 for was shorter than that for 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 kinetics generated the longer τ 2 for in hypoxia, with consequent contribution of anaerobic lactic metabolism to the energy balance in exercise transient, witnessed by the increase in [La]b. [Copyright &y& Elsevier]

Abstract: We tested the hypothesis that, after bed rest, maximal oxygen consumption () decreases more upright than supine, because of adequate cardiovascular response supine, but not upright. On 9 subjects, we determined and maximal cardiac output () upright and supine, before and after (reambulation day upright, the following day supine) 35-day bed rest, by classical steady state protocol. Oxygen consumption, heart rate (f H ) and stroke volume (Q st ) were measured by a metabolic cart, electrocardiography and Modelflow from pulse pressure profiles, respectively. We computed as f H times Q st , and systemic oxygen flow () as times arterial oxygen concentration, obtained after haemoglobin and arterial oxygen saturation measurements. Before bed rest, all parameters at maximal exercise were similar upright and supine. After bed rest, was lower (p<0.05) than before, both upright (−38.6%) and supine (−17.0%), being 30.8% higher supine than upright. Maximal Q st decreased upright (−44.3%), but not supine (+3.7%), being 98.9% higher supine than upright. Maximal decreased upright (−45.1%), but not supine (+9.0%), being higher supine than upright (+98.4%). Maximal decreased upright (−37.8%), but not supine (+14.8%), being higher (+74.8%) upright than supine. After bed rest, the cardiovascular response (i) did not affect supine, (ii) partially explained the decrease upright, and (iii) caused the differences between postures. We speculate that impaired peripheral oxygen transfer and/or utilisation may explain the decrease supine and the fraction of decrease upright unexplained by cardiovascular responses. [Copyright &y& Elsevier]

Abstract: The hypothesis that changes in gravity acceleration (a g) affect the linear relationships between oxygen consumption and mechanical power so that at any , increases linearly with a g was tested under conditions where the weight of constant-mass legs was let to vary by inducing changes in a g in a human centrifuge. The effects of a g on the relationship were studied on 14 subjects at two pedalling frequencies (f p, 1.0 and 1.5Hz), during four work loads on a cycle ergometer (25, 50, 75 and 100W) and at four a g levels (1.0, 1.5, 2.0 and 2.5 times normal gravity). increased linearly with . The slope did not differ significantly at various a g and f p, suggesting invariant mechanical efficiency during cycling, independent of f p and a g. Conversely, the y-intercept of the relationship, defined as constant b, increased linearly with a g. Constant b is the sum of resting plus internal metabolic power . Since the former was the same at all investigated a g, the increase in constant b was entirely due to an increase in . Since the versus lines had similar slopes, the changes in entirely explained the higher at each , as a g was increased. In conclusion, the effects of a g on are mediated through changes in , and not in or in resting . [Copyright &y& Elsevier]

Abstract: To assess the effects of respiratory muscle training (RMT) on maximum oxygen uptake () in normoxia and hypoxia, 9 healthy males (age 24±4 years; stature 1.75±0.08m; body mass 72±9kg; mean±SD) performed on different days maximal incremental tests on a cycle ergometer in normoxia and normobaric hypoxia (), 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 ( and , respectively) at maximal exercise were significantly higher than pre-training condition (+12 and +13%, respectively; P <0.05). Accordingly, alveolar O2 partial pressure () after RMT significantly increased by ∼10%. Nevertheless, arterial and did not change with respect to pre-training condition. In conclusion, RMT improved respiratory function but did not have any effect on , neither under normoxic nor hypoxic condition. In hypoxia, the significant increase in and at maximum exercise after training lead to higher alveolar but not arterial values, revealing an increased A-a gradient. This result, according to the theoretical models of limitation, seems to contradict the lack of increase in hypoxia, suggesting a possible role of increased ventilation-perfusion mismatch. [Copyright &y& Elsevier]

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 ([Formula: see text]) 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 [Formula: see text] 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., (© 2022. The Author(s).)

Purpose: 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., Methods: 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., Results: 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 P < 0.0001), but not at 40 rpm (16 ± 5 vs 11 ± 17 W, P > 0.99). Ėint increased with the third power of fp both in WET and DRY (R2 = 0.49 and 0.91, respectively)., Conclusions: 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., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Introduction: 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., Competing Interests: Dr Alessia Riglietti reports grants from ABREOC (Scientific Research Advisory Board of the Ente Ospedaliero Cantonale), Doctor PierLuigi Crivelli Foundation and Cecilia Augusta Foundation, during the conduct of the study. Dr Carlo W Cereda is a member of the iSchemaView Medical and Scientific Advisory Board, but this institution played no role in current research . Prof. Dr Marco Pons report grants from ABREOC, Dr Pieruigi Crivelli Foundation and Cecilia Augusta Foundation, during the conduct of the study. The authors have no other financial support or conflicts of interest to declare., (© 2021 Riglietti et al.)

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.

The steady state concept implies that the oxygen flow is invariant and equal at each level along the respiratory system. The same is the case with the carbon dioxide flow. This condition has several physiological consequences, which are analysed. First, we briefly discuss the mechanical efficiency of exercise and the energy cost of human locomotion, as well as the roles played by aerodynamic work and frictional work. Then we analyse the equations describing the oxygen flow in lungs and in blood, the effects of ventilation and of the ventilation - perfusion inequality, and the interaction between diffusion and perfusion in the lungs. The cardiovascular responses sustaining gas flow increase in blood are finally presented. An equation linking ventilation, circulation and metabolism is developed, on the hypothesis of constant oxygen flow in mixed venous blood. This equation tells that, if the pulmonary respiratory quotient stays invariant, any increase in metabolic rate is matched by a proportional increase in ventilation, but by a less than proportional increase in cardiac output., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This article reviews the concept of maximal oxygen consumption ([Formula: see text]) from the perspective of multifactorial models of [Formula: see text] limitation. First, I discuss procedural aspects of [Formula: see text] measurement: the implications of ramp protocols are analysed within the theoretical work of Morton. Then I analyse the descriptive physiology of [Formula: see text], evidencing the path that led to the view of monofactorial cardiovascular or muscular [Formula: see text] 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 [Formula: see text] limitation is reinforced by multifactorial models, since cardiovascular oxygen transport provides most of the [Formula: see text] 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.

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Intraoperative analysis of the sentinel lymph node (SLN) status is currently performed in patients with breast cancer (BC) undergoing surgery. Axillary node (AN) metastases are present in up to 60% of cases, but the risk is only 30% in patients with early stage (T1) BC. The aim of this study was to evaluate the usefulness of 99mTc-sestamibi scintimammography (SSM), axillary ultrasonography (US) and US-guided fine-needle aspiration (FNA) cytology together in detecting axillary metastases preoperatively and their potential role in reducing the number of SLN procedures., Patients and Methods: A series of 86 consecutive women (median age 57 years, range 30-72) with confirmed BC and clinically negative nodes (T1N0) underwent both SSM and US prior to surgery. US-guided FNA cytology was performed in all the patients with suspicious AN on US, or positive SSM and ultrasonographically visualized enlarged nodes., Results: Final pathology showed 4 pT1bN0, 1 pT1bN1, 60 pT1cN0 and 21 pT1cN1 BC. The sensitivity, specificity, and accuracy were 59.1%, 93.7% and 84.9% for SSM, 63.6%, 90.6% and 83.7% for US, and 72.7%, 97.8% and 90.7% for SSM and US together. Using FNA cytology the specificity reached 100%, but the sensitivity did not increase. A combined method using radioisotope and blue dye was used for SLN biopsy. The procedure was omitted in patients with FNA cytology showing AN metastases (N = 14, 16.3%) and they underwent level I-II axillary dissection, as well as those with positive SLN biopsy on frozen section (8 out of 72, 11.1%)., Conclusion: In patients with BC, preoperatively selected by SSM and US in whom US-guided axillary FNA cytology has shown the presence of AN metastases, the SLN biopsy can be avoided and AN dissection should be the primary procedure.

We tested the hypothesis that vagal withdrawal plays a role in the rapid (phase I) cardiopulmonary response to exercise. To this aim, in five men (24.6+/-3.4 yr, 82.1+/-13.7 kg, maximal aerobic power 330+/-67 W), we determined beat-by-beat cardiac output (Q), oxygen delivery (QaO2), and breath-by-breath lung oxygen uptake (VO2) at light exercise (50 and 100 W) in normoxia and acute hypoxia (fraction of inspired O2=0.11), because the latter reduces resting vagal activity. We computed Q from stroke volume (Qst, by model flow) and heart rate (fH, electrocardiography), and QaO2 from Q and arterial O2 concentration. Double exponentials were fitted to the data. In hypoxia compared with normoxia, steady-state fH and Q were higher, and Qst and VO2 were unchanged. QaO2 was unchanged at rest and lower at exercise. During transients, amplitude of phase I (A1) for VO2 was unchanged. For fH, Q and QaO2, A1 was lower. Phase I time constant (tau1) for QaO2 and VO2 was unchanged. The same was the case for Q at 100 W and for fH at 50 W. Qst kinetics were unaffected. In conclusion, the results do not fully support the hypothesis that vagal withdrawal determines phase I, because it was not completely suppressed. Although we can attribute the decrease in A1 of fH to a diminished degree of vagal withdrawal in hypoxia, this is not so for Qst. Thus the dual origin of the phase I of Q and QaO2, neural (vagal) and mechanical (venous return increase by muscle pump action), would rather be confirmed.

We tested whether the kinetics of systemic O(2) delivery (QaO(2)) at exercise start was faster than that of lung O(2) uptake (Vo(2)), being dictated by that of cardiac output (Q), and whether changes in Q would explain the postulated rapid phase of the Vo(2) increase. Simultaneous determinations of beat-by-beat (BBB) Q and QaO(2), and breath-by-breath Vo(2) 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). Vo(2) was determined using Grønlund's algorithm. Q was computed from BBB stroke volume (Q(st), from arterial pulse pressure profiles) and heart rate (f(h), electrocardiograpy) and calibrated against a steady-state method. This, along with the time course of hemoglobin concentration and arterial O(2) saturation (infrared oximetry) allowed computation of BBB QaO(2). The Q, QaO(2) and Vo(2) kinetics were analyzed with single and double exponential models. f(h), Q(st), Q, and Vo(2) increased upon exercise onset to reach a new steady state. The kinetics of QaO(2) had the same time constants as that of Q. The latter was twofold faster than that of Vo(2). The Vo(2) 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 Q changes fully explained the phase I of Vo(2) increase. We suggest that in unsteady states, lung Vo(2) is dissociated from muscle O(2) consumption. The two components of Q and QaO(2) 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.

Modelflow, when applied to non-invasive fingertip pulse pressure recordings, is a poor predictor of cardiac output (Q, litre x min(-1)). The use of constants established from the aortic elastic characteristics, which differ from those of finger arteries, may introduce signal distortions, leading to errors in computing Q. We therefore hypothesized that peripheral recording of pulse pressure profiles undermines the measurement of Q with Modelflow, so we compared Modelflow beat-by-beat Q values obtained simultaneously non-invasively from the finger and invasively from the radial artery at rest and during exercise. Seven subjects (age, 24.0 +/- 2.9 years; weight, 81.2 +/- 12.6 kg) rested, then exercised at 50 and 100 W, carrying a catheter with a pressure head in the left radial artery and the photoplethysmographic cuff of a finger pressure device on the third and fourth fingers of the contralateral hand. Pulse pressure from both devices was recorded simultaneously and stored on a PC for subsequent Q computation. The mean values of systolic, diastolic and mean arterial pressure at rest and exercise steady state were significantly ( P < 0.05) lower from the finger than the intra-arterial catheter. The corresponding mean steady-state Q obtained from the finger (Qporta) was significantly ( P < 0.05) higher than that computed from the intra-arterial recordings (Qpia). The line relating beat-by-beat Qporta and Qpia was y =1.55 x -3.02 ( r2 = 0.640). The bias was 1.44 litre x min(-1) and the precision was 2.84 litre x min(-1). The slope of this line was significantly higher than 1, implying a systematic overestimate of Q by Qporta with respect to Qpia. Consistent with the tested hypothesis, these results demonstrate that pulse pressure profiles from the finger provide inaccurate absolute Q values with respect to the radial artery, and therefore cannot be used without correction with a calibration factor calculated previously by measuring Q with an independent method.

The heart rate (HR) and O(2) uptake (VO(2)) responses to cycle ergometer exercise and the role of O(2) transport in limiting submaximal and maximal aerobic performance were assessed in 33 heart transplant recipients (HTR) [14 children (P-HTR), 11 young adults (YA-HTR) and 8 middle-age adults (A-HTR)] and in 28 age-matched control subjects (CTL). In 7 P-HTR ("responders") the HR response to the onset of exercise (on-response) was as fast as that of CTL, whereas in all other patients ("non-responders") the HR on-response was typical of the denervated heart. Compared with non-responder P-HTR, responder P-HTR were also characterized by a normal peak HR (177+/- 16 vs. 151+/- 25 beats/min), an equally slow time constant for the VO(2) on-response (tau: 54 +/- 11 vs. 62+/- 13 s) and a similar low (approximately 60% of that of CTL) peak VO(2) (28 +/- 7 vs. 26 +/- 10 ml/kg per min). On the other hand non-responder YA-HTR and A-HTR were characterized by a relatively low peak HR (151 +/- 21 and 144 +/- 29 beats/min, respectively), a slow tau for the on-response (63 +/- 12 and 70 +/- 11 s) and a low peak (28 +/- 7 and 19 +/- 6 ml/kg per min). In conclusion, a sizeable number of paediatric patients (responder P-HTR) may reacquire the normal HR response to exercise, both in terms of kinetics and maximal level. Despite the almost complete recovery of cardiovascular function, and, probably, oxygen delivery, both the kinetics of the VO(2) on-response and the maximal aerobic power of the responder P-HTR were similar to those of non-responder P-HTR. The latter finding is probably attributable to peripheral limitations, due to inborn and/or pharmacological muscle deterioration.

The plasma concentration of noradrenaline ([NA]) is higher than that of adrenaline ([A]) both in normal subjects and in heart transplant recipients (HTR). Since in both groups the myocardial density of beta1-adrenergenic receptors is much greater than that of beta2-adrenergenic receptors, the chronotropic response of a denervated heart to changes in plasma [NA] and [A] in the absence of reinnervation should be similar to that of agonist stimulation of beta1-receptors. To test this hypothesis, 17 HTR and 9 healthy subjects (CTL) performed incremental exercise on a cycle ergometer to voluntary exhaustion. Heart rate (HR) was recorded by electrocardiography. [NA] and [A] were measured by high-pressure liquid chromatography at rest and at increasing workloads (w). In both groups, HR and [NA+A] increased with w, and HR with [NA+A]. Normalized HR values, plotted against the logarithm of [NA+A], fitted significantly logistic curves. The affinity constants were different, i.e. 2599+/-350 and 487+/-37 ng.l(-1), for HTR and CTL, respectively. The chronotropic effect of changes in [NA+A] in HTR was similar to that of combined beta1- and beta2-adrenergic activation evoked by applying isoprenaline to isolated heart myocytes (Brodde OE, Pharmacol Ther 60:405-430, 1993). These findings suggest that over time sympathetic reinnervation and the modulation of beta-receptors may take place in HTR, ruling out the hypothesis of persistent heart denervation.