Baroreflex responses during dry resting and exercise apnoeas in air and pure oxygen.

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.

Breath holding as an example of extreme hypoventilation: experimental testing of a new model describing alveolar gas pathways.

NEW FINDINGS: What is the central question of this study? We modelled the alveolar pathway during breath holding on the hypothesis that it follows a hypoventilation loop on the O2 -CO2 diagram. What is the main finding and its importance? Validation of the model was possible within the range of alveolar gas compositions compatible with consciousness. Within this range, the experimental data were compatible with the proposed model. The model and its characteristics might allow predictions of alveolar gas composition whenever the alveolar ventilation goes to zero; for example, static and dynamic breath holding at the surface or during ventilation/intubation failure in anaesthesia. ABSTRACT: According to the hypothesis that alveolar partial pressures of O2 and CO2 during breath holding (BH) should vary following a hypoventilation loop, we modelled the alveolar gas pathways during BH on the O2 -CO2 diagram and tested it experimentally during ambient air and pure oxygen breathing. In air, the model was constructed using the inspired and alveolar partial pressures of O2 ( PIO2 and 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.

Differences in alveolo-capillary equilibration in healthy subjects on facing O2 demand.

Oxygen diffusion across the air-blood barrier in the lung is commensurate with metabolic needs and ideally allows full equilibration between alveolar and blood partial oxygen pressures. We estimated the alveolo-capillary O2 equilibration in 18 healthy subjects at sea level at rest and after exposure to increased O2 demand, including work at sea level and on hypobaric hypoxia exposure at 3840 m (PA ~ 50 mmHg). For each subject we estimated O2 diffusion capacity (DO2), pulmonary capillary blood volume (Vc) and cardiac output ([Formula: see text]). We derived blood capillary transit time [Formula: see text] and the time constant of the equilibration process ([Formula: see text], ß being the slope of the hemoglobin dissociation curve). O2 equilibration at the arterial end of the pulmonary capillary was defined as [Formula: see text]. Leq greately differed among subjects in the most demanding O2 condition (work in hypoxia): lack of full equilibration was found to range from 5 to 42% of the alveolo-capillary PO2 gradient at the venous end. The present analysis proves to be sensible enough to highlight inter-individual differences in alveolo-capillary equilibration among healthy subjects.

Air blood barrier phenotype correlates with alveolo-capillary O2 equilibration in hypobaric hypoxia.

The O2 diffusion limitation across the air blood barrier (DO2 and subcomponents Dm and Vc) was evaluated in 17 healthy participants exposed to hypobaric hypoxia (HA, 3840m, PIO2 ∼90mmHg). A 10% decrease in alveolar volume (VA) in all participants suggested the development of sub-clinical interstitial lung edema. In >80% of participants DO2/VA increased, reflecting an individual strategy to cope with the hypoxia stimulus by remodulating Vc or Dm. Opposite changes in Dm/Vc ratio were observed and participants decreasing Vc showed reduced alveolar blood capillary transit time. The interplay between diffusion and perfusion (cardiac output) was estimated in order to investigate the individual adaptive response to hypoxia. It appears remarkable that despite individual differences in the adaptive response to HA, diffusion limitation did not exceed ∼11% of the alveolar-venous PO2 gradient, revealing an admirable functional design of the air-blood barrier to defend the O2 diffusion/perfusion function when facing hypobaric hypoxia corresponding to 50mmHg decreased PAO2.

Reappraisal of DLCO adjustment to interpret the adaptive response of the air-blood barrier to hypoxia.

DLCO measured in hypoxia must be corrected due to the higher affinity (increase in coefficient θ) of CO with Hb. We propose an adjustment accounting for individual changes in the equation relating DLCO to subcomponents Dm (membrane diffusive capacity) and Vc (lung capillary volume): 1/DLCO=1/Dm+1/θVc. We adjusted the individual DLCO measured in hypoxia (HA, 3269m) by interpolating the 1/DLCO to the sea level (SL) 1/θ value. Nineteen healthy subjects were studied at SL and HA. Based on the proposed adjustment, DLCO increased in HA in 53% of subjects, reflecting the increase in Dm that largely overruled the decrease in Vc. We hypothesize that a decrease in Vc (buffering microvascular filtration) and the increase in Dm (possibly resulting from a decrease in thickness of the air-blood barrier) represent the anti-edemagenic adaptation of the lung to hypoxia exposure. The efficiency of this adaptation varied among subjects as DLCO did not change in 31% of subjects and decreased in 16%.

Mild training program in metabolic syndrome improves the efficiency of the oxygen pathway.

In sedentary patients suffering of metabolic syndrome, we evaluated the effects of mild exercise program (EP) on the efficiency of the oxygen delivery system. The prescription of exercise (40 min/session, 3 times/week) was tailored at workload corresponding to ∼90% individual anaerobic threshold (AT). EP improved significantly by ∼10% peak values of oxygen consumption (VO2) and heart rate (HR). Furthermore, in response to steady state workload at 90% AT, EP shortened the time constant of VO2, HR and the ratio VO2/HR (reflecting arterio-venous O2 concentration difference) by ∼6s. EP also decreased the elastic respiratory work due to a change in breathing pattern implying a larger contribution of respiratory rate, at the expense of tidal volume during exercise hyperventilation. In all subjects the perceived fatigue (Borg) decreased after training. This study supports a positive effect of a mild EP for the adaptive response of the oxygen chain to face metabolic needs compatible with daily life in patients affected by metabolic syndrome.

Regional differences in bronchial reactivity assessed by respiratory impedance.

We used the Impulse Oscillometric System (IOS) to gain information concerning the distribution of hyper-reactivity along the bronchial tree during methacholine challenge test (MCT). 37 subjects underwent MCT until reaching the provocative dose (PD20). At each dose, we estimated respiratory resistance at 5 and 20Hz (R5, R20), and reactance at 5Hz (X5). In non-responsive subjects (N=14) no changes in R5, R20, and X5 were observed during MCT. In responsive subjects, a wide spectrum of responses was found concerning frequency dependence and PD20. We describe two phenotypes representing the extremes of response. For PD20>400µg (N=13), MCT caused equal changes of resistance/reactance on varying oscillation frequencies, suggesting a homogeneous bronchoconstriction along the bronchial tree. For PD20<200µg (N=10), a remarkable frequency dependence was observed, with increase in R5, no change in R20, and decrease in X5, suggesting hyper-responsiveness of the distal airways paralleled by a change in visco-elastic properties of lung parenchyma.