Ventilation–perfusion inequality and carbon dioxide sensitivity in hypoxaemic chronic obstructive pulmonary disease (COPD) and effects of 6 months of long‐term oxygen treatment (LTOT)

The aim of our study was to find out how blood gas disturbances in stable, eucapnic, severe chronic obstructive pulmonary disease (COPD) patients with an arterial oxygen tension (PaO₂) value of 7·7 (6·1–8·4) kPa are affected by ventilation–perfusion (V_A/Q) relationships and carbon dioxide (CO₂) sensitivity and how these parameters are influenced by 6 months of long‐term oxygen treatment (LTOT). V_A/Q ratios were measured using the multiple inert gas elimination technique (MIGET). Mouth occlusion pressure 0·1 s after onset of inspiration (Pi0·1) and minute ventilation (V_E) were measured to assess respiratory drive response (ΔPi0·1/ΔPCO₂) and hypercapnic ventilatory response (HCVR) to CO₂ rebreathing. At the start of LTOT, a normal median respiratory drive response level of 1·2 (0·2–2·3) cm H₂O/kPa and a low median HCVR as compared with healthy individuals (P<0·001) were found. However, 7·9 (0–29·8)% of the V_E, was directed towards hypoperfused lung areas. The dispersion of ventilation (log SDV; 0·47–1·76), and the dispersion of perfusion (log SDQ; 0·66–1·07) were wider than normal. The PaO₂ level correlated inversely with mean V_A/Q ratio for ventilation (V mean) and shunt. The PaCO₂ level correlated inversely with HCVR and vital capacity. After 6 months of LTOT, no significant changes in daytime blood gas levels, CO₂‐sensitivity or V_A/Q ratios were found. V_E tended to be reduced by 1·0 l min^–1. Conclusions: An elevated V mean and probably shunting are important contributing factors for the reduced PaO₂ and hypercapnic ventilatory response is a major determinant of PaCO₂ in eucapnic stable hypoxaemic COPD. Six months of LTOT does not affect blood gases, CO₂ sensitivity or ventilation–perfusion relationships.     

Leg uptake of calcitonin gene‐related peptide during exercise in spinal cord injured humans

Exercise‐induced increases in cardiac output (CO) and oxygen uptake (VO₂) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function – such as calcitonin gene related peptide (CGRP) – may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 ± 2 min to fatigue. Voluntary cycling performed both at VO₂ similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33·8 ± 3·1 pmol l^?1 (rest) to 39·5 ± 4·3 (14%, P<0·05)) with a mean extraction over the working leg of 10% (P<0·05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33·2 ± 3·8 to 46·9 ± 3·6 pmol l^?1, P<0·05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0·05). The exercise induced increase in leg blood flow was 10–12 fold in both spinal cord injured and controls at similar VO₂ (P<0·05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 ± 7 to 132 ± 15 bpm) compared with controls and tetraplegics (P<0·05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.     

Lung aeration during sleep in patients with obstructive sleep apnoea

Background: Previous studies have indicated that patients with obstructive sleep apnoea (OSA) have altered ventilation and lung volumes awake and the results suggest that this may be a determinant of severity of desaturations during sleep. However, little is known about regional lung aeration during sleep in patients with OSA. Methods: Twelve patients with OSA were included in the study. Computed tomography was used to study regional lung aeration during wakefulness and sleep. Lung aeration was calculated in ml gas/g lung tissue in four different regions of interest (ROI_1–4), along the border of the lung from ventral to dorsal. Results: Lung aeration in the dorsal (dependent) lung region (ROI₄) was lower during sleep compared to wakefulness 0·78 ± 0·19 versus 0·88 ± 0·19 (mean ± SD) ml gas/g lung tissue (P = 0·005). Associations were found between awake expiratory reserve volume and change in lung aeration from wakefulness to sleep in ROI₄ (r = ?0·69; P = 0·012). In addition, the change in lung aeration in the dorsal region correlated to sleep time (r = 0·69; P = 0·014) but not to time in supine position. The difference in lung aeration between inspiration and expiration (i.e. ventilation), was larger in the ventral lung region when expressed as ml gas per g lung tissue. In two patients it was noted that, during on‐going obstructive apnoea, lung aeration tended to be increased rather than decreased. Conclusions: Aeration in the dorsal lung region is reduced during sleep in patients with OSA. The decrease is related to lung volume awake and to sleep time.     

Pulmonary clearance of inhaled [99Tcm]DTPA: effects of ventilation pattern

Summary. While a rise in lung volume is known to increase the pulmonary clearance of technetium-99m-labelled dietylene triamine pentaacetate ([⁹⁹Tc^m]DTPA), little interest has been focused on the effects of changes in ventilation frequency, tidal volume and airway pressure. We studied adult, anaesthetized and intubated rabbits during three ventilation patterns (VP) using pressure controlled ventilation (Servo Ventilator 900C). VP was either deep slow (f=20 min^-1, tidal volume (V_T) = 30 ± 4 ml kg^-1 and positive end-expiratory pressure (PEEP) = 0·2 kPa [VP 20/ 0·2, n= 8]) or rapid shallow (f=80 min^-1, V_T= 11 ±2 ml kg^-1 and PEEP = 0·2 or 0·4 kPa [VP 80/0·2, n= 6 and VP 80/0·4, n= 6]). The mean airway pressure was similar at VP 20/0·2 and VP 80/0·4. During administration of [⁹⁹Tc^m]DTPA aerosol all animals were ventilated under the same conditions (f=40 min^-1 and PEEP = 0·2 kPa). The pulmonary clearance rate expressed as the half-life time (T^1/2) of [⁹⁹Tc^m]DTPA was at VP 80/0·2 = 113 ± 31 min, at VP 80/0·4 = 70 ± 24 min (P < 0·01 compared to VP 80/0·2) and at VP 20/0·2 = 36± 18 min (P <0·001 compared to VP 80/0·2 and P <0·01 compared to VP 80/0·4). We conclude that the pulmonary clearance of [⁹⁹Tc^m]DTPA increases

• 1 during rapid shallow ventilation when PEEP is increased from 0·2 to 0·4 kPa;
• 2 during deep slow ventilation relative to rapid shallow ventilation even when the mean airway pressure is similar.

     

Changes in transfer factor of the lung in response to bronchodilatation

Measurement of the transfer factor for carbon monoxide (T_LCO) is a widely used clinical lung function test. Although it is frequently applied in patients with bronchial obstruction, there is little information on the effects of bronchodilatation on the test. We therefore measured T_LCO in 40 patients before and after inhalation of terbutaline. T_LCO was measured with the single‐breath technique in 20 patients and with the intra‐breath technique in 20 patients. T_LCO was also measured in 20 healthy subjects with the single‐breath technique. Forced expiratory volume (FEV₁) increased from 2·9 ± 1·1 to 3·2 ± 1·2 l in patients with bronchial obstruction in response to terbutaline inhalation. T_LCO increased from 8·2 ± 2·6 to 8·6 ± 2·7 mmol min^–1 kPa^–1 (P< 0·001) and alveolar volume (V_A) from 5·74 ± 1·21 to 5·90 ± 1·21 l (P<0·001). There was no difference between the single‐breath and the intra‐breath techniques. There was little change in FEV₁ in the healthy subjects in response to terbutaline. T_LCO increased from 10·2 ± 2·1 to 10·5 ± 2·2 mmol min^–1 kPa^–1 (P< 0·01), but there was no change in V_A. The increase in T_LCO in patients may partly be explained by improved distribution of the inhaled gas. In healthy subjects, terbutaline may increase pulmonary capillary volume. We conclude that bronchodilatation results in a small increase in T_LCO in patients with light to moderate bronchoconstriction as well as in healthy subjects. The effect is small and should in most cases be simple to account for in the interpretation of pulmonary function tests, provided the patient’s treatment is known.     

Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years or older

In the elderly, standing can frequently be accompanied by blood pressure (BP) changes and cerebral symptoms such as dizziness, fall, or even syncope, but this may vary from day‐to‐day. Therefore, we aimed to investigate the reproducibility of orthostatic responses of cerebral cortical oxygenation and systemic haemodynamics in elderly subjects. In 27 healthy elderly subjects (age 70–84 years), changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR) and stroke volume (SV) were continuously monitored by Finapres (Finger Arterial Pressure), and changes in oxyhaemoglobin ([O₂Hb]) and deoxyhaemoglobin ([HHb]) concentrations were continuously measured over the right frontal cortex by near infrared spectroscopy (NIRS) during supine rest and 10 min of active standing on two separate occasions. SBP and DBP increased by 6·7 ± 15·4 mmHg (P<0·05, mean ± SD) and 8·2 ± 6·4 mmHg (P<0·01), respectively, whereas HR increased by 9·5 ± 5·0 bpm (P<0·01) and SV decreased by –8·3 ± 7·4 ml (P<0·01) during standing on the first occasion. [O₂Hb] decreased by –3·9 ± 2·9 μmol l^–1 (P<0·01), while [HHb] increased by 1·8 ± 2·2 μmol l^–1 (P<0·01). Group‐averaged orthostatic changes in cortical oxygenation and systemic haemodynamics were very similar on the two occasions, although an intraindividual variation was found. Cortical oxygenation changes were not accompanied by severe cerebral symptoms. Active standing induced reproducible group‐averaged frontal cortical oxygenation declines in healthy elderly subjects, although an intraindividual day‐to‐day variability was present, possibly related to the variability of orthostatic BP responses. These findings indicate that cerebral autoregulation fails to compensate completely for postural changes in elderly subjects, which might predispose elderly subjects to ischaemic cerebral symptoms.     

Respiratory drive during carbachol challenge in allergic sheep

Diaphragmatic activity is the standard assessment of respiratory neural output but is difficult to measure and cannot be used for long‐term clinical monitoring. The tidal breathing minute ventilation ( ) and mean inspiratory flow (V_T/t_I) reflect respiratory drive and can be monitored non‐invasively using respiratory inductive plethysmography (RIP). Recent findings indicate that peak inspiratory acceleration (PIA) correlates to diaphragmatic activity during CO₂ rebreathing in piglets. The aim of the present study was to assess whether tidal breathing peak inspiratory acceleration reflects respiratory drive during carbachol challenge. Aerosolized carbachol was administered to 15 allergic sheep until pulmonary resistance increased by at least 400%. After threshold dose, slight increases in
and V_T/t_I were seen (8 and 5%, respectively; P=NS), while PIA increased by 30% (P<0·05). The change in PIA was closely correlated to changes in
and V_T/t_I (r=0·73, P<0·01 and r=0·88, P<0·001, respectively). In conclusion, peak inspiratory acceleration reflected respiratory drive during bronchoprovocation. Further, this new measure of drive has the potential to accurately estimate drive in chronic obstructive lung disease where intrinsic positive end expiratory pressure prevents accurate selection of beginning inspiration necessary for computation of, e.g. V_T/t_I.     

Intracellular pH,intrauterine growth and the insulin resistance syndrome

Defects of both sodium–hydrogen exchange (NHE) and sodium–lithium countertransport (SLC) have been described in subjects at increased risk of coronary heart disease (CHD). Sodium transport is linked to the regulation of cell volume, intracellular pH and cell growth, which may explain aspects of this association. However, impaired growth in early life is also linked to adult CHD, and ‘programmed’ alterations of cell behaviour are postulated to be responsible for this. In this study, therefore, we examined whether NHE or SLC in adults are predicted by anthropometric measures at birth, as well as being associated with insulin resistance syndrome (IRS) variables in adulthood. Red cell SLC was measured in 26 adults, and NHE in dermal fibroblasts from another 15 subjects characterized anthropometrically at birth. SLC activity correlated with LDL cholesterol, triglycerides and urate (r=0·42 – 0·49; 0·05 > P>0·01), but not birth anthropometry. NHE V_max correlated with plasma insulin (r=0·80; P<0·001), but birth weight was unrelated to V_max, K_m or Hill coefficient for H⁺_i. However, pH_i correlated with birth weight (r=0·74; P=0·002), insulin sensitivity (r=0·52; P<0·05), fasting glucose (r=–0·52; P<0·05) 2 h insulin (r=0·51; P<0·05) 2 h glucose (r=–0·54; P<0·05). In conclusion, red cell SLC is related to IRS variables, but not with birth weight measures. In contrast, low intracellular pH_i is related to both low birth weight and adult insulin resistance, suggesting it might be a ‘programmed’ cell phenotype, although this is not apparently explained by altered NHE kinetics.     

Upright body position and weight loss improve respiratory mechanics and daytime oxygenation in obese patients with obstructive sleep apnoea

To determine whether upright body position and weight loss would improve daytime gas exchange in moderately obese patients with obstructive sleep apnoea (OSAS), 13 patients with mild or moderate OSAS were studied before and after weight loss. Pulmonary function tests, arterial blood gases and respiratory gas analysis were measured prior to and after a very low calorie diet (VLCD) period of six weeks. Arterial blood gases were measured in supine and standing positions and closing volume in supine and sitting positions before and after weight loss. In the upright position, there was a significant increase in PaO₂ (P<0·005) accompanied by a significant decrease in alveolar–arterial PO₂ difference (P<0·005) and closing volume (P<0·05). The median weight loss was 11 kg (range 5–18). The number of desaturation episodes (four percentage units or more per hour during sleep) (ODI₄) decreased (P<0·01) after weight loss. The change in PaO₂ with weight loss correlated with the decrease in ODI₄ (r=0·73, P<0·01). The increase in expiratory reserve volume (ERV) was closely related to the amount of weight lost (r=0·895, P<0·01). The results indicate that weight loss and upright body position improved daytime respiratory mechanics and gas exchange in obese patients with OSAS. The findings suggest that obesity plays an important role in the pathogenesis of daytime gas exchange disturbances in obese OSAS patients. The adoption of a more upright sleep posture might improve nocturnal oxygenation in obese patients with OSAS.     

A prolonged postinspiratory pause enhances CO2 elimination by reducing airway dead space

Background: CO₂ elimination per breath (V_CO2,T) depends primarily on tidal volume (V_T). The time course of flow during inspiration influences distribution and diffusive mixing of V_T and is therefore a secondary factor determining gas exchange. To study the effect of a postinspiratory pause we defined ‘mean distribution time’ (MDT) as the mean time given to inspired gas for distribution and diffusive mixing within the lungs. The objective was to quantify changes in airway dead space (V_Daw), slope of the alveolar plateau (SLOPE) and V_CO2,T as a function of MDT in healthy pigs. Methods: Ten healthy pigs were mechanically ventilated. Airway pressure, flow and partial pressure of CO₂ were recorded during resetting of the postinspiratory pause from 10% (baseline) to, in random order, 0, 5, 20 and 30% of the respiratory cycle. The immediate changes in V_Daw, SLOPE, V_CO2,T, and MDT after resetting were analyzed. Results: V _Daw in percent of V_T decreased from 29 to 22%, SLOPE from 0·35 to 0·16 kPa per 100 ml as MDT increased from 0·51 to 1·39 s. Over the same MDT range, V_CO2,T increased by 10%. All these changes were statistically significant. Conclusion: MDT allows comparison of different patterns of inspiration on V_Daw and gas exchange. Estimation of the effects of an altered ventilator setting on exchange of CO₂ can be done only after about 30 minutes, while the transient changes in V_CO2,T may give immediate information. MDT affects gas exchange to an important extent. Further studies in human subjects in health and in disease are needed.     

Effects of oxygen supplementation on cerebral oxygenation during exercise in chronic obstructive pulmonary disease patients not entitled to long-term oxygen therapy

Background: The rate of change (Δ) in cerebral oxygenation (COx) during exercise is influenced by blood flow and arterial O₂ content (CaO₂). It is currently unclear whether ΔCOx would (i) be impaired during exercise in patients with chronic obstructive pulmonary disease (COPD) who do not fulfil the current criteria for long‐term O₂ therapy but present with exercise‐induced hypoxaemia and (ii) improve with hyperoxia (FIO₂ = 0·4) in this specific sub‐population. Methods: A total of 20 non‐hypercapnic men (FEV₁ = 47·2 ± 11·5% pred) underwent incremental cycle ergometer exercise tests under normoxia and hyperoxia with ΔCOx (fold‐changes from unloaded exercise in O₂Hb) being determined by near‐infrared spectroscopy. Pulse oximetry assessed oxyhaemoglobin saturation (SpO₂), and impedance cardiography estimated changes in cardiac output (ΔQT). Results: Peak work rate and ΔCOx in normoxia were lower in eight O₂‘desaturators’ compared with 12 ‘non‐desaturators’ (P<0·05). Area under ΔCOx during sub‐maximal exercise was closely related to SpO₂ decrements in ‘desaturators’ (r = 0·92, P<0·01). These patients showed the largest improvement in peak exercise capacity with hyperoxia (P<0·05). Despite a trend to lower sub‐maximal ΔQT and mean arterial pressure with active intervention, ΔCOx was significantly improved only in this group (0·57 ± 0·20 versus 2·09 ± 0·42 for ‘non‐desaturators’ and ‘desaturators’, respectively; P<0·05). Conclusions: ΔCOx was impaired in non‐hypoxaemic patients with COPD who desaturated during exercise. Hyperoxic breathing was able to correct for these abnormalities, an effect related to enhanced CaO₂ rather than improved central haemodynamics. This indicates that O₂ supplementation ameliorates exercise COx in patients with COPD who are not currently entitled to ambulatory O₂ therapy.     

Distribution of interstitial fluid pressure and fluid volumes in hind‐limb skin of rats: relation to meridians?

To determine the distribution of interstitial fluid pressure (P_i) and volume (V_i), and to relate the distribution of these parameters to the distribution of potential meridians located by measurement of electrical impedance, we measured P_i, extracellular fluid (V_e) and plasma volumes (V_p) in 14 pre‐defined skin areas, 2 × 2 mm, and in concave and convex regions on the hind‐limb and groin of rats in control conditions. P_i was measured with sharpened glass capillaries connected to a servo‐controlled counter‐pressure system, while V_e and V_p were determined as the extravascular distribution spaces of ⁵¹Cr‐EDTA and ¹²⁵I‐human serum albumin, respectively. V_i was calculated as V_e – V_p, and V_w as the difference between skin wet and dry weight. Grand mean P_i averaged –0·81 mmHg (SD 0·83, n=95). P_i in skin was significantly higher in lateral and medial parts of the medial aspect of hind‐limb compared to pressures in the intermediate area (P<0·05). Pressures in the concave groin and the convex knee area were more negative and positive, respectively, than in the flat intermediate central hind‐limb area. There was a significantly higher V_i (P<0·05) and V_w (P<0·05) in the lateral side than that in the medial side. V_p was higher medially and laterally than in the intermediate area (P<0·05 for both comparisons), and correlated positively and significantly with P_i (r=0·66, P<0·05). No correlation was found between P_i and electrical impedance. The study suggests that the distribution of P_i, V_i, V_p and V_w is heterogeneous in hind‐limb skin at a macroscopic level without obvious relations to potential meridians.     

Validation of the acetylene rebreathing method for measurement of cardiac output at rest and during high-intensity exercise

The use of the acetylene rebreathing method to estimate cardiac output (CO) during high-intensity exercise, which may be influenced by recirculation of acetylene, has not been validated. This study was designed to validate the acetylene rebreathing method to measure CO during high-intensity exercise using the direct Fick method. CO was measured at rest and during exercise at 25%, 50%, 75% and 90% of the nine subjects maximum oxygen uptake (VO _2max) by the direct Fick and acetylene rebreathing method. CO measured by the acetylene rebreathing method correlated with work rate (r=0·90, P<0·01) and with oxygen uptake (r=0·94, P<0·01). The correlation coefficient of CO between both methods was r=0·91 (P<0·01). There was no significant difference in CO measured by each method at rest as well as at each work rate. The difference in CO between each method was greater at lower CO than at higher CO. At 90% of VO _2max, the CO measured by acetylene rebreathing was nearly identical to that measured by the Fick method. It can be concluded that acetylene rebreathing for measurement of CO is valid not only at rest but also during exercise, especially during high-intensity exercise.     

Potassium and ventilation during positive and negative work inpatients with chronic obstructive pulmonary disease

In patients with chronic obstructive pulmonary disease (COPD),reduced ventilatory reserves limit exercise tolerance. In these patients, the ventilatoryrequirements of eccentric exercise (negative work, W_neg) are lower thanthose of concentric exercise (positive work, W_pos) at similar workloads.In this study, we investigated the relationship between plasma potassium levels and ventilationduring W_pos and W_neg in these patients. Twelvepatients with stable COPD [mean (SD) FEV₁ 46% (16) of predicted]performed W_pos and W_neg on a cycle ergometer(6 min of exercise; interval ≥1 h) in a randomized order at a constant workload of50% of the individual maximum (positive) work capacity. Minute ventilation (V_E) and arterial plasma potassium concentration ([K⁺]_a) were measured at rest, and at 1-min intervals during exercise and during 3 min ofrecovery. V_E increased less during W_neg thanduring W_pos [6 (range 3–26) vs. 18 (range 8–28) l min^?1; P<0·01]. V_E during W_neg was reduced in proportion to VCO ₂.The increase in [K⁺]_a during W_pos and W_neg [0·45 (range 0·26–0·75) and0·34 (range 0·1–0·97) mM ] did not differsignificantly. V_E was closely correlated with VCO ₂ during both types of exercise. V_E was also closelycorrelated with [K⁺]_a, but the slope of the relationship between[K⁺]_a and V_E was steeper during W_pos than during W_neg [39·1 (range15·2–88·6) vs. 18·3 (range7·2–37·3) l min^?1 mM ^?1; P=0·012]. In contrast, the slope of the relationship betweenVCO ₂ and V_E was similar during bothtypes of exercise [27?8 (range 19·2–37·1) vs. 32·1 (range19·8–48·4)]. Thus, for a given increase in [K⁺]_a, the increase in V_E was significantly less during W_neg. In patients with COPD, potassium did not explain the difference inexercise ventilation between W_neg and W_pos, andmay not play a significant role in the control of breathing during low-intensity exercise.     

Influence of alveolar ventilation changes on calculated gastric intramucosal pH and gastric-arterial PCO2 difference

Objective: To evaluate the influence of changes in alveolar ventilation on the following tonometry-derived variables: gastric intramucosal CO₂ tension (PtCO₂), gastric arterial CO₂ tension difference (P_gapCO₂), gastric intramucosal pH (pHi) and arterial pH-pHi difference (pH_gap). Design: Clinical prospective study. Setting: A medical intensive care unit in a university hospital. Patients: Ten critically ill, mechanically ventilated patients requiring hemodynamic monitoring with pulmonary artery catheter. Interventions: Gastric tonometer placement. A progressive increase in tidal volume (V_T) from 7 to 10 ml/kg followed by an abrupt return to baseline V_T level. Measurements and main results: Tonometer saline PtCO₂ and hemodynamic data were collected hourly at various V_T levels: H0 and H0' (baseline V_T = 7 ml/kg), H1 (V_T = 8 ml/kg), H2 (V_T = 9 ml/kg), H3 (V_T = 10 ml/kg), H4 (baseline V_T). During the “hyperventilation phase” (H0-H3), pHi (p < 0.01) and pH_gap (p < 0.05) increased but P_gapCO₂ remained unchanged. Cardiac output (CO) was not affected by ventilatory change. During the “hypoventilation phase” (H3-H4), pHi fell from 7.27 ± 0.11 to 7.23 ± 0.09 (p < 0.01) and P_gapCO₂ decreased from 16 ± 5 mmHg to 13 ± 4 mmHg (p < 0.05). V_T reduction was associated with a significant cardiac output elevation (p < 0.05). Conclusions: PaCO₂ and PtCO₂ are similarly influenced by the changes in alveolar ventilation. Unlike pHi, the P_gapCO₂ is not affected by ventilation variations unless CO changes are associated. Received: 15 June 1998 Final revision received: 21 October 1998 Accepted: 16 November 1998     

Induction of acute metabolic acid/base changes in humans

The aim of this study was to induce acute metabolic acid/base changes of ≥2 mequiv · l^–1 change in base excess (BE) to aid future investigations of respiratory parameters under these conditions. Ammonium chloride (NH₄Cl) was administered to induce acidification and furosemide was used to induce alkalization. Nine healthy volunteers (six men and three women aged 35 ± 18 years) ingested a calculated amount of NH₄Cl at t=0 and a repeat dose after 60 min. Eight healthy volunteers (three men and five women aged 37 ± 16 years) consumed 40 mg of furosemide. Arterialized capillary blood gases were measured at t=0, 30, 60, 90, 120 and 180 min. In the case of acute metabolic acidosis, the target acidification of 2 mequiv · l^–1 was attained after 30 min and the greatest change was achieved at 90 min: –4·9 (2·2) mequiv · l^–1. In the case of acute metabolic alkalosis, the target alkalization of 2 mequiv · l^–1 was reached between 120 and 180 min and the greatest change was seen at 180 min: +2·2 (1·4) mequiv · l^–1. Significant (P<0·05) changes in acidification compared with baseline BE values were found between 60 and 180 min; significant (P<0·05) changes in alkalization were found between 120 and 150 min. Paco₂ did not change significantly in either condition. We conclude that NH₄Cl and furosemide induce a steady state of pure metabolic acid/base conditions in humans, which is buffered in an isocapnic manner.     

Autonomic nervous function at rest in aerobically trained and untrained oldermen

Therelationship between aerobictraining, vagal influence on the heart and ageing was examined by assessing aerobic fitness andresting heart rate variability in trained and untrained older men. Subjects were 11 trained cyclistsand runners (mean age=6±61·6 years) and 11 untrained, age-matchedmen (mean age=66±1·2 years). Heart rate variability testing involvedsubjects lying supine for 25 min during which subjects’ breathing was paced andmonitored (7·5 breaths min^?1). Heart rate variability was assessedthrough time series analysis (HRV_ts) of the interbeat interval. Results indicated thattrained older men (3·55±0·21 l min^?1) hadsignificantly (P<0·05) greater VO _2maxthan that of control subjects (2·35±0·15 l min^?1).Also, trained older men (52±1·8 beats min^?1) hadsignificantly (P<0·05) lower supine resting heart rate than that of controlsubjects (65±4·2 beats min^?1). HRV_ts at highfrequencies was greater for trained men (5·98±0·22) than for untrainedmen (5·23±0·32). These data suggest that regular aerobic exercise inolder men is associated with greater levels of HRV_ts at rest.     

No change in the regional distribution of tidal volume during lateral posture in mechanically ventilated patients assessed by electrical impedance tomography

We assessed the distribution of regional lung ventilation during moderate and steep lateral posture using electrical impedance tomography (EIT) in mechanically ventilated patients. Seven patients were placed on a kinetic treatment table. An elastic belt containing 16 electrodes was placed around the chest and was connected to the EIT device. Patients were moved to left and right lateral positions in a stepwise (10°) mode up to 60°. EIT images [arbitrary units (AU)] were generated and scanned for assessment of relative ventilation distribution changes [tidal volume (V_T)]. A calibration procedure of arbitrary units (AUs) versus ventilator‐derived V_T performed in all patients during three predefined positions (supine, 60°‐left dependent and 60°‐right‐dependent) showed a significant correlation between V_T in supine, left and right lateral positions with the corresponding AUs (r² = 0·356, P<0·05). Changes in V_T were calculated and compared to supine position, and specific regions of interest (ROIs) were analysed. In our study, in contrast to recent findings, a change in lateral positions did not induce a significant change in regional tidal volume distribution. In right lateral positions, a broader variation of V_T with a trend towards an increase in the dependently positioned lung was observed in comparison with supine. Lateral positioning promotes the redistribution of ventilation to the ventral regions of the lung. The use of EIT technology might become a helpful tool for understanding and guiding posture therapy in mechanically ventilated patients.     

Metabolic cost of locomotion during treadmill walking with blood flow restriction

We explored whether interval walking with blood flow restriction (BFR) increases net metabolic cost of locomotion in healthy young men at their optimal walking speed. We also determined whether decreased walking economy resulting from BFR might be accompanied by an increase in ventilation relative to VO₂ and VCO₂. Finally, we examined possible relationships between the changes in ratings of perceived exertion (RPE) and those obtained in minute ventilation (V_E) during walking with BFR. Eighteen healthy men (age: 22·5 ± 3·4 years) performed graded treadmill exercise to assess VO_2max. In a randomized fashion, participants also performed five bouts of 3‐min treadmill exercise with and without BFR at their optimal walking speed. Walking with BFR elicited an overall increase in net VO₂ (10·4%) compared with that seen in the non‐BFR condition (P<0·05). The participants also demonstrated greater V_E and V_E/VO₂ values while walking with BFR (P<0·05). Conversely, V_E/VCO₂ was similar between conditions at each walking bout. We found no significant correlation between the changes in V_E and RPE induced by walking with BFR (r = 0·38, P>0·05). Our results indicate that (i) BFR decreases net walking economy in healthy young men, even at their optimal walking speed; (ii) heightened ventilatory drive may explain a small proportion of BFR effects on walking economy; and (iii) the ventilatory responses to BFR walking may be largely independent of changes in perceived exertion and are likely matched to the flux of CO₂ between muscles and respiratory centres.     

Endurance training,overtraining and baroreflex sensitivity in female athletes

We examined heavy training-induced changes in baroreflex sensitivity, plasma volume and resting heart rate and blood pressure variability in female endurance athletes. Nine athletes (experimental training group, ETG) increased intense training (70–90% VO _2max) volume by 130% and low-intensity training (<70% VO _2max) volume by 100% during 6–9 weeks, whereas the corresponding increases in six control athletes (CG) were 5% and 10% respectively. Maximal oxygen uptake (VO _2max) in the ETG and CG did not change, but in five ETG athletes VO _2max decreased from 53·0 ± 2·2 (mean ± SEM) (CI 46·8–59·2) ml kg^–1 min^–1 to 50·2 ± 2·3 (43·8–56·6) ml kg^–1 min^–1 (P<0·01), indicating overtraining. Baroreflex sensitivity (BRS) measured using the phenylephrine technique and blood pressure variability (BPV) did not change, but the low-frequency power of the R–R interval variability increased in the ETG (P<0·05). The relative change in plasma volume was 7% in the ETG and 3% in the CG. The changes in BRS did not correlate with the changes in plasma volume, heart rate variability and BPV. We conclude that heavy endurance training and overtraining did not change baroreflex sensitivity or BPV but significantly increased the low-frequency power of the R–R interval variability during supine rest in female athletes as a marker of increased cardiac sympathetic modulation.