Exercise-induced hypoxemia in athletes: Role of inadequate hyperventilation

Summary These experiments examined the exercise-induced changes in pulmonary gas exchange in elite endurance athletes and tested the hypothesis that an inadequate hyperventilatory response might explain the large intersubject variability in arterial partial pressure of oxygen (P _a0₂) during heavy exercise in this population. Twelve highly trained endurance cyclists [maximum oxygen consumption (VO_2max) range = 65-77 ml·kg^–1·min^–1] performed a normoxic graded exercise test on a cycle ergometer toVO_2max at sea level. During incremental exercise atVO_2max 5 of the 12 subjects had ideal alveolar to arterial P02 gradients (P _A-aO₂) of above 5 kPa (range 5-5.7) and a decline from restingP _aO₂ (P _aO₂) 2.4 kPa or above (range 2.4-2.7). In contrast, 4 subjects had a maximal exercise (P _A-aO₂) of 4.0-4.3 kPa with P _aO₂ of 0.4-1.3 kPa while the remaining 3 subjects hadP _A-aO₂ of 4.3-5 kPa with P _aO₂ between 1.7 and 2.0 kPa. The correlation between P_AO₂ andP _aO₂ atVO_2max was 0.17. Further, the correlation between the ratio of ventilation to oxygen consumption VSP _aO₂ and arterial partial pressure of carbon dioxide VSP _aO₂ atVO_2max was 0.17 and 0.34, respectively. These experiments demonstrate that heavy exercise results in significantly compromised pulmonary gas exchange in approximately 40% of the elite endurance athletes studied. These data do not support the hypothesis that the principal mechanism to explain this gas exchange failure is an inadequate hyperventilatory response.     

Cardiac sympathetic denervation does not change the load dependence of the left ventricular end-systolic pressure/volume relationship in dogs

It has been shown that in the intact canine heart the left-ventricular end-systolic pressure/volume relation (ESPVR) depends on loading conditions: an increase in arterial vascular resistance causes a leftwards shift and a steeper slope of the ESPVR, suggesting an increased inotropic state. Our purpose was to investigate the possible contribution of the sympathetic nervous system to this load sensitivity of the ESPVR, using intact, but denervated, hearts with normal coronary perfusion and afterload. We used two types of loading intervention: venous volume infusion and gradual occlusion of the descending aorta. ESPVRs were obtained in six anaesthetized open-chest dogs, both before and after bilateral ablation of the stellate ganglia. To exclude the influence of heart rate changes, bilateral vagotomy was performed and the heart was paced. The absence of (unpaced) heart rate changes in response to pressure alterations was used to confirm total denervation. Left ventricular pressure was measured with a micromanometer and volume with a conductance catheter. ESPVRs were essentially linear and characterized by their slope (E _es) and volume intercept at 12 kPa (V ₁₂). We found that E _es (P<0.0001) and V₁₂ (P<0.05) were both significantly different during pressure and volume interventions (0.67±0.29 and 0.41±0.18 kPa/ml for E _es and 16.2±8.2 and 18.2±8.4ml for V₁₂ respectively). Denervation did not significantly affect the parameters of the ESPVR obtained by either volume infusion or aortic occlusion. Two-way analysis of variance revealed no significant interactive effect between denervation and intervention, indicating that the sympathetic nervous system does not influence the load dependency of the ESPVR. The dP/dt _max: EDV relationship behaved similarly. These results suggest that load dependency is an intrinsic property of the myocardium.     

Differences in mouth occlusion pressure and breathing pattern between arm and leg incremental exercise

The aim of the study was to compare breathing pattern, mouth occlusion pressure, mean inspiratory flow and the ratio of mouth occlusion pressure to mean inspiratory flow at the same power output and carbon dioxide output during arm and leg incremental exercise. Mouth occlusion pressure was used as an index of inspiratory neuromuscular activity and its ratio to mean inspiratory flow as an index of the ‘effective’ impedance of the respiratory system. Eight normal subjects performed two incremental exercise tests, one with arms, the other with legs, on different weeks and in randomized order, and on two identical cycle ergometers. The power output was increased by steps of 25 W for arms and 50 W for legs every 4 min until exhaustion. At the same power output, oxygen consumption, carbon dioxide output, ventilation, mean inspiratory flow, mouth occlusion pressure, ‘effective’ impedance (P<0.001) and respiratory frequency (P<0.01) were higher during arm exercise than during leg exercise, whereas inspiratory time (P<0.05) and expiratory time (P<0.01) were lower. At the same carbon dioxide output, mouth occlusion pressure, ventilation, ‘effective’ impedance (P<0.001) and respiratory frequency (P<0.01) were higher and expiratory time (P<0.05) was lower during arm exercise. In conclusion, the higher inspiratory neuromuscular activity and impedance of the respiratory system during arm exercise and the differences observed in ventilation and breathing pattern at equal carbon dioxide output seem related to the differences in exercising muscle afferents and the presence of an increased load due to contraction of rib cage muscles to stabilize posture.     

Comparison of arterial,end-tidal and transcutaneous PCO2 during moderate exercise and external C02 loading in humans

Summary Static relationships between arterial, transcutaneous[/p] and end-tidal PCO₂ (P _aCO₂, P _tc CO ₂, P _etCO₂) as well as the dynamic relationship between P _etCO₂ and P _tcCO₂ were studied during moderate bicycle ergometer exercise with and without external C0₂ loading. The exercise pattern consisted of 5-min intervals of constant power at 40 W and 100 W and 900 s of randomised changes between these two power levels. The external CO₂ loading was achieved by means of controlled variations of inspiratory gas compositions aimed at a constant P _etCO₂ of 6.5 kPa (49 mm Hg). The P_etO2 was regulated at 17.3 kPa (130 mm Hg). Under steady-state conditions all PCO₂ parameters showed close linear relationships. P _aCO₂/P _tcCO₂ was near to identity while the P _etCO₂ systematically overestimated changes in P _aCO₂. No relationship showed a significant influence of the exercise intensity. Transients of P _tcCO₂ are considerably slower than P _etCO₂ transients. The dynamic relationship between both parameters was found to be independent of whether internal or external C0₂ loadings were applied. It is concluded that the combination of P _etCO₂ and P _tcCO₂ measurements allows an improved non-invasive assessment of P _aCO₂. While P _etC0₂ better reflects the transients, P _tcCO₂ can be employed to determine slow changes of the absolute P _aCO₂.     

Increased load on the respiratory muscles in obstructive sleep apnea

We wished to quantify, in patients with obstructive sleep apnoea (OSA), the activity of the respiratory muscles in relation to upper airway occlusion and patency in sleep. We hypothesized that particular levels of neuromuscular activation are directly associated with upper airway patency. 21 patients with previously diagnosed OSA and 21 healthy control subjects underwent respiratory muscle testing and polysomnography. Neural respiratory drive, as measured by the electromyogram of the diaphragm (EMG_di) was elevated in the obese OSA patients, awake and supine (13.1(5.6)%max), compared to normal subjects (mean (SD) 8.1(2.3)%max, p < 0.01). During unobstructed breathing in sleep (stage N2) normal subjects had an EMG_di of 7.7(3.9) compared to 22.8(19.2)%max in the OSA group (p < 0.001). Prior to airway occlusion, EMG_{submandibular} and EMG_di dropped markedly, and then, following occlusion, increased progressively to their highest levels at airflow onset. Patients with OSA require specific and increased levels of neural respiratory drive to sustain ventilation in sleep.     

Ventilatory response to oscillating and non-oscillatingPa CO 2 in the anesthetized cat

Summary In 11 adult cats, lightly anesthetized with chloralose-urethane, blood from both common carotid arteries was led into a plastic chamber of 15–20 ml and returned to the carotids at a point 1.5 cm more cranial. By doing so arterial blood was assumed to pool within the chamber and lose itsP _{CO 2} oscillations which are normally known to exist as a result of the respiratory cycle. In control periods blood bypassed the chamber, thus maintaining respiratoryP _{CO 2} oscillations. Spontaneous ventilation was measured spirometrically. The animals were breathing pure O₂.Results. 1. When the sinus (carotid) nerves were intact or sectioned there was no significant difference in ventilation before or after switching from non-oscillating to oscillatingPa _{CO 2}. 2. When the vertebral arteries were ligated a drop in ventilation occurred after turning to oscillatingPa _{CO 2} which was followed by a slight rise above control values after 30–50 sec. This phenomenon was independent of sinus nerve integrity. Thus in hyperoxie condition the smallPa _{CO 2} oscillations known to occur in phase with respiration do not seem to provide a respiratory stimulus to resting ventilation above that generated by the mean level ofPa _{CO 2}. The ventilatory depression after vertebral artery ligation must at this time remain unexplained.     

Removal of Cardiac Beat Artifact in Esophageal Pressure Measurement via a Modified Adaptive Noise Cancellation Scheme

Information on volume–pressure relationships of human lungs is usually based on indirect determination of intrapleural pressure (P_ip) obtained from the esophagus. Unfortunately, cardiac beat artifact frequently corrupts measurement of esophageal pressure (P_es). In this study, we presented a modified adaptive noise cancellation (MANC) scheme for removing the cardiac beat artifact in the P_es signal. The proposed methodology used an airflow signal as the reference signal with least-mean-square method as the adaptive algorithm. The results of six experiments on two Brown–Norway rats showed a significant reduction of the apparent cardiac pulsation with minimal distortion of the P_es signal. The MANC filter also showed evidence of peak suppression at integer multiples of heart rate in the fast Fourier transform of the P_es signal while leaving the remaining spectrum largely unperturbed. A t-test method and the ratio of standard deviation to mean (std/mean) statistics of airway resistance (R_aw) values were used to evaluate the performance of the MANC filter. In all six experiments, a reduction of std/mean of R_aw by 12.5%–68% was obtained, indicating the effectiveness of the proposed scheme. © 2001 Biomedical Engineering Society. PAC01: 8780-y, 8719Hh, 8719Uv     

Hyperpnoea and CO2 sensitivity of the respiratory centres during exercise

Summary The aim of this study was to specify whether exercise hyperpnoea was related to the CO₂ sensitivity of the respiratory centres measured during steady-state exercise of mild intensity. Thus, ventilation , breathing pattern [tidal volume (V _T), respiratory frequency (f), inspiratory time (T _I), total time of the respiratory cycle (T _TOT),V _T/T _I,T _I/T _TOT] and CO₂ sensitivity of the respiratory centres determined by the rebreathing method were measured at rest (SCO_{2 re}) and during steady-state exercise (SCO_{2 ex}) of mild intensity [CO₂ output =20 ml·kg⁻¹·min⁻¹] in 11 sedentary male subjects (aged 20–34 years). The results showed that SCO_{2 re} and SCO_{2 ex} were not significantly different. During exercise, there was no correlation between and SCO_{2 ex} and, for the same , all subjects had very close values normalized for body mass (bm), regardless of their SCO_{2 ex} ( =1.44 l·min⁻¹·kg⁻¹ SD 0.10). A highly significant positive correlation between SCO_{2 ex} andV _T (normalised for bm) (r=0.80,P<0.01),T _I (r=0.77,P<0.01) andT _TOT (r=0.77,P<0.01) existed, as well as a highly significant negative correlation between SCO_{2 ex} and (normalised for bm^−0.25) (r=−0.73,P<0.01). We conclude that the hyperpnoea during steady-state exercise of mild intensity is not related to the SCO_{2 ex}. The relationship between breathing pattern and SCO_{2 ex} suggests that the breathing pattern could influence the determination of the SCO_{2 ex}. This finding needs further investigation.     

Mechanisms compensating for altered resistance to respiration during muscular exercise in man

Alterations in respiratory parameters following the substitution of a helium-oxygen (He−O₂) or sulfur hexafluoride-oxygen (SF₆−O₂) mixture for air were analyzed during the first 10 respiratory cycles in human volunteers exposed to either of these mixtures for 3 min at rest and during forced respiration. Both at rest and during moderate physical exercise neither the volume of pulrnonary ventilation nor the partial carbon dioxide pressure differed significantly in the subjects breathing air, He−O₂, or SF₆−O₂. When the He−O₂ mixture was substituted for air, the forces developed by the inspiratory muscles, the work of breathing, the activity of the parasternal intercostal muscles, and the central inspiratory activity were all reduced, whereas substitution of the SF₆−O₂ mixture for air led to significant increases in these four parameters. It is concluded that compensatory responses of the respiratory system to altered density of the gaseous medium develop on the basis of the afferent impulse traffic from mechanoreceptors of the lungs and respiratory muscles and also on account of segmental reflexes and intrinsic properties of the muscle fibers themselves. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 247–251, September, 1995 Presented by A. D. Ado, Member of the Russian Academy of Medical Sciences     

Interpretation of gas-blood ratio inP O 2polarography

Summary The differences inP _{O 2}readings between gas and blood were studied with a Clark-type electrode in the range of 38.5 to 713 mm HgP _{O 2}.The tonometered blood samples were taken in two different ways. The results showed that the gas-blood ratior _b(equilibrating gasP _{O 2}reading/equilibrated bloodP _{O 2}reading) depended not only on the sampling method but also on theP _{O 2}range: it varied from 1.005 to 1.032 for aP _{O 2}of 96.5 mm Hg, and from 1.040 to 1.081 for aP _{O 2}of 713 mm Hg according to the sampling procedure.A theoretical analysis demonstrated that the variation ofr _bwith the bloodP _{O 2}can be attributed to the influence of the degree of oxygen saturation of the hemoglobin on theP _{O 2}gradient existing in the blood diffusion boundary layer adhering to the electrode membrane.This work was supported by grants from the High Authority of the European Coal and Steel Community and from the Fonds de la Recherche Scientifique Médicale, Belgium.     

Effect of AA-2414, a thromboxane A2 receptor antagonist, on airway inflammation in subjects with asthma

Background: Asthma is a chronic inflammatory disease of the airways. The chemokines are potent chemoattractants for eosinophils and other types of cells associated with allergic inflammation. AA-2414, a new thromboxane A₂ receptor antagonist, reduces bronchial hyperresponsiveness in asthmatic subjects, but its mechanism of action is unclear. Objective: We tested the hypothesis that the beneficial effects of AA-2414 in asthma result from reduction in the number of inflammatory cells infiltrating the airway associated with inhibition of chemokine release. Methods: We studied bronchial biopsy specimens from 31 asthmatic subjects before and after oral treatment with AA-2414 (80 mg/day) or matched placebo for 4 months in a double-blind manner. Biopsy specimens were examined by immunohistochemistry. Each subject recorded symptom score and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. Results: After treatment, significant improvements in symptom score (P < .05), PEF (P < .01), diurnal variation of PEF (P < .01), and bronchial responsiveness (P < .01) were observed in the AA-2414 group compared with the placebo group. These improvements were accompanied by a significant decrease in the number of submucosal EG2⁺ eosinophils (P < .05). There was also a reduction in the number of cells expressing RANTES (P < .05) and macrophage inflammatory protein (MIP)-1α (P < .05) in the epithelium and of cells expressing monocyte chemotactic protein-3 (P < .01), RANTES (P < .05), MIP-1α (P < .01), and eotaxin (P < .01) in the submucosa in the AA-2414 treatment group. A significant correlation was found between the number of EG2⁺ eosinophils and numbers of monocyte chemotactic protein-3⁺ (r_s = 0.52, P < .005), MIP-1α⁺ (r_s = 0.34, P < .05), and eotaxin⁺ cells (r_s = 0.47, P < .01) in the submucosa. There was a significant negative correlation between the increase in bronchial responsiveness and the change in number of submucosal EG2⁺ cells (r_s = –0.65, P < .001). Conclusions: These findings suggest that AA-2414 treatment of patients with asthma may inhibit activated eosinophil infiltration in part by modulating the expression of chemokines in bronchial tissues. (J Allergy Clin Immunol 1999;103:1054-61.)     

Does the threshold of transcutaneous partial pressure of carbon dioxide represent the respiratory compensation point or anaerobic threshold?

On reaching the respiratory compensation point (RCP) during rapidly increasing incremental exercise, the ratio of minute ventilation (V_E) to CO₂ output (VCO₂) rises, which coincides with changes of arterial partial pressure of carbon dioxide (P _aCO₂). Since P _aCO₂ changes can be monitored by transcutaneous partial pressure of carbon dioxide (PCO_2,tc) RCP may be estimated by PCO_2,tc measurement. Few available studies, however, have dealt with comparisons between PCO_2,tc threshold (T _AT) and lactic, ventilatory or gas exchange threshold (V _AT), and the results have been conflicting. This study was designed to examine whether this threshold represents RCP rather than V _AT. A group of 11 male athletes performed incremental excercise (25 W · min^–1) on a cycle ergometer. The PCO_2,tc at (44°C) was continuously measured. Gas exchange was computed breath-by-breath, and hyperaemized capillary blood for lactate concentration ([la^–]_b) and P _aCO₂ measurements was sampled each 2 min. The T _AT was determined at the deflection point of PCO_2,tc curve where PCO_2,tc began to decrease continuously. The V _AT and RCP were evaluated with VCO₂ compared with oxygen uptake (VO₂) and V_E compared with the VCO₂ method, respectively. The PCO_2,tc correlated with P _aCO₂ and end-tidal PCO₂. At T _AT, power output [P, 294 (SD 40) W], VO₂ [4.18 (SD 0.57)l · min^–1] and [la^–] [4.40 (SD 0.64) mmol · l^–1] were significantly higher than those at V _AT[P 242 (SD 26) W, VO₂ 3.56 (SD 0.53) l · min^–1 and [la^–]_b 3.52 (SD 0.75), mmol · l^–1 respectively], but close to those at RCP [P 289 (SD 37) W; VO₂ 3.97 (SD 0.43) l · min^– and [la^–]_b 4.19 (SD 0.62) mmol · l^–1, respectively]. Accordingly, linear correlation and regression analyses showed that P, VO₂ and [la^–]_b at T _AT were closer to those at RCP than at V _AT. In conclusion, the T _AT reflected the RCP rather than V _AT during rapidly increasing incremental exercise.     

Ventilatory responses to hypercapnia in divers and non-divers: effects of posture and immersion

The aim of this study was to determine the effects on respiratory drive of two factors, one mechanical (lung volume) and one chemical (sensitivity to hypercapnia), that are involved in determining the breath-hold duration (BHD). Functional residual capacity was measured by helium dilution with the subject seated in air, seated in water and in the prone position in water. Hyperoxic hypercapnia rebreathing (Read's method) was carried out under identical environmental conditions to assess the effects of CO₂ pressure on respiratory centre output by measuring ventilation, mean inspiratory flow and occlusion pressure. Sixteen healthy volunteers were tested, 8 trained divers and 8 non-divers. Functional residual capacity decreased for the postures seated in water (30.8%–34.8%) and for prone position in water (20.3%–20.9%) when compared to the posture seated in air (P<0.0001), all subjects pooled. No difference was found between groups. The slopes of the linear regression, which characterised the sensitivity to CO₂ and were determined with the rebreathing tests, revealed differences between the two populations (ventilation: P<0.0001; mean inspiratory flow: P<0.05). No difference was found for occlusion pressure or between the different postures. These results confirmed a lower sensitivity to CO₂ for trained divers. This adaptation was shown to decrease respiratory centre activity at the origin of the breath-hold breaking point. The immersion, did not influence respiratory drive, despite a decrease in lung volumes. The authors suggest that these findings may be explained by a specific apnoea training and a pronounced bradycardia in immersion. Electronic Publication     

Repeated normoxic hyperbaric exposures induce haemodynamic and myocardial changes in rats

Summary The effect of repeated exposure to ambient pressures of 5 bar (500 kPa), in atmospheres comprising normal partial pressures of oxygen [0.2 bar (20 kPa)] and nitrogen [0.8 bar (80 kPa)] and 4 bar (400 kPa) helium, on cardiac function and morphology was assessed in conscious rats. Ten test rats underwent chamber dives daily for 40 consecutive days, and ten control rats were exposed in the same chamber for an equal period of time, but in air at 1 bar (100 kPa). Cardiac output (Q_c) and myocardial blood flow (Q_myocardial) were determined by the microsphere method. After 40 days, the body mass was 7% greater in the control than in the test rats (P<0.05), although they were given exactly the same amount of standard food. The test rats had a significantly higher (7% absolute, 12% ventricular mass to body mass, P<0.05) heart mass (left ventricular myocardium, including the ventricular septum) than the control rats. The percentage tissue dry mass of the right and left ventricles was equal in the two groups. Microscopic examination revealed a number of small focal necroses in the left ventricle of the test rats but none in the control rats. The left ventricular pressure (LVP) and the maximum velocity of LVP increase (contractility) and decrease were significantly increased (25%–96%, P<0.001) in the pre-exposed compared to the control rats at 1 bar (100 kPa). The systolic arterial pressure, heart rate and respiratory frequency were similar in the two groups at 1 bar (100 kPa). The LVP and + dP/dt increased linearly and in parallel in both groups during compression, although at 5 bar (500 kPa) the test rats had reached a significantly higher LVP and + dP/dt level. However, the heart rate was unchanged in both groups. The pre-exposed rats had a higher left Q_myocardial [1 bar (100 kPa)=33%, P<0.05; and 5 bar (500 kPa)=maximum 40%, P<0.05] than the control rats. The systolic arterial blood pressure also increased during compression to its maximum after 20 min at 5 bar (500 kPa) in both groups. The mean arterial pressure, respiratory frequency, end-diastolic pressure and Q_c were unchanged throughout the experiments. A pressure drop of 42 mmHg (5.6 kPa) between the left ventricle and the arteries would suggest stenosis in the aortic valve region in the test rats. In conclusion, the cardiac function as well as myocardial mass and morphology were changed after 40 consecutive exposures to 5 bar (500 kPa) in conscious rats.     

Effect of ageing on the ventilatory response and lactate kinetics during incremental exercise in man

We investigated the effects of age on breathing pattern, mouth occlusion pressure, the ratio of mouth occlusion pressure to mean inspiratory flow, and venous blood lactate kinetics during incremental exercise. Mouth occlusion pressure was used as an index of inspiratory neuromuscular activity, and its ratio to mean inspiratory flow was used as an index of the “effective impedance” of the respiratory system. Nine elderly male subjects [mean (SD) age: 68.1 (4.8) years] and nine young male subjects [mean (SD) age: 23.4 (1.3) years] performed an incremental exercise test on a bicycle ergometer. After a warm-up at 30 W, the power was increased by 30 W every 1.5 min until exhaustion. Our results showed that at maximal exercise, power output, breathing pattern, and respiratory exchange values, with the exception of tidal volume and the “effective impedance” of the respiratory system, were significantly higher in the young subjects. The power output and oxygen consumption values at the anaerobic threshold were also significantly higher in the young men. At the same power output, the elderly subjects showed significantly higher values for minute ventilation, respiratory equivalents for oxygen uptake and carbon dioxide output (CO₂), mean inspiratory flow, occlusion pressure and lactate concentration than the young subjects. At the same CO₂ below the anaerobic threshold (0.5, 0.75, 1.00 and 1.25 l · min⁻¹), minute ventilation and lactate concentration were also significantly higher in the elderly subjects. We observed a significantly higher minute ventilation at CO₂ values of 0.5, 0.75, 1.00 (P < 0.001) and 1.25 l · min⁻¹ (P < 0.05) in the elderly men, and a significantly higher lactate concentration at CO₂ values of 1.00 (P < 0.05) and 1.25 l · min⁻¹ (P < 0.01). In conclusion, the ventilatory response in elderly subjects is elevated in comparison with that in young subjects, both below and above the anaerobic threshold. This study demonstrates for the first time that this ventilatory increase, both below and above the threshold, is partly due to an increased lactate concentration. Received: 30 March 1999 / Accepted: 24 June 1999     

Absence of long-term modulation of ventilation by dead-space loading during moderate exercise in humans

The stability of arterial PCO₂ (P_aCO₂) during moderate exercise in humans suggests a CO₂-linked control that matches ventilation (_E) to pulmonary CO₂ clearance (CO₂). An alternative view is that _E is subject to long-term modulation (LTM) induced by hyperpnoeic history. LTM has been reported with associative conditioning via dead-space (V_D) loading in exercising goats (Martin and Mitchell 1993). Whether this prevails in humans is less clear, which may reflect differences in study design (e.g. subject familiarisation; V_D load; whether or not _E is expressed relative to CO₂; choice of P_aCO₂ estimator). After familiarisation, nine healthy males performed moderate constant-load cycle-ergometry (20 W-80 W-20 W; <lactate threshold, _L): day 1, pre-conditioning, n=3; day 2, conditioning (V_D=1.59 l, doubling _E at 20 W and 80 W), n=8 with 10 min rest between tests; and, after 1 h rest, post-conditioning, n=3. Gas exchange was determined breath-by-breath. Post-conditioning, neither the transient [phase 1, phase 2 (1, 2)] nor steady-state _E exercise responses, nor their proportionality to CO₂, differed from pre-conditioning. For post-conditioning trial 1, steady-state _E was 28.1 (4.7) l min^–1 versus 29.1 (3.8) l min^–1 pre-conditioning, and mean-alveolar PCO₂ (a validated P_aCO₂ estimator) was 5.53 (0.48) kPa [41.5 (3.6) mmHg] versus 5.59 (0.49) kPa [41.9 (3.7) mmHg]; the 1 _E increment was 4.2 (2.9) l min^–1 versus 5.2 (1.9) l min^–1; the 2 _E time-constant () was 64.4 (24.1) s versus 64.1 (25.3) s; _E/CO₂ was 1.12 (0.04) versus 1.10 (0.04); and the _E-CO₂ slope was 21.7 (3.4) versus 21.2 (3.2). In conclusion, we could find no evidence to support ventilatory control during moderate exercise being influenced by hyperpnoeic history associated with dead-space loading in humans.     

The influence on the breathing pattern in man of moderate levels of continuous positive and negative airway pressure and of positive end-expiratory pressure during air and CO2 inhalation

The purpose of this study was to determine in man the effect on the breathing pattern of continuous positive (CPAP), continuous negative (CNAP) and positive end-expiratory (PEEP) airway pressure during air breathing and CO₂ inhalation. Six subjects were exposed to CPAP, CNAP and PEEP 0.5 kPa, while five subjects were exposed to CPAP and CNAP 0.8 kPa. End-expiratory lung volume increased during CPAP 0.8 kPa and decreased during CNAP 0.8 kPa. CPAP induced more extensive changes in the ventilatory pattern, and the changes in each parameter were larger than observed during CNAP and PEEP at the same pressure level. In contrast to previous reports we found the effect of CO₂ inhalation combined with the effect of pressure breathing to be not stronger than additive. Even moderate CPAP induced alveolar hyperventilation with marked reduction in arterial PCO₂ (PaCO₂) when breathing air. With increasing fraction of CO₂ in the inspiratory gas, the difference in PaCO₂ between CPAP and no CPAP disappeared. PEEP also affected the breathing pattern in that it induced an increase in mean inspiratory flow and mean expiratory flow and a reduction in inspiratory duration. Occurrence of ventilatory pauses depended on whether mouthpiece or facemask was used. CPAP and CNAP did not influence the occurrence of pauses, while PEEP prolonged post-expiratory pauses. We conclude that CPAP, CNAP and PEEP induce active ventilatory responses in man and that strong mechanisms are involved during CPAP since PaCO₂ is markedly reduced.     

Transmural gradient of tissue gas tensions in the canine left ventricular myocardium during coronary clamping and reactive hyperemia

Mass spectrometry was used for the continuous, simultaneous and quantitative measurement of oxygen (PO₂) and carbon dioxide (PCO₂) partial pressures in the subendocardial and subepicardial layers of the left ventricle in 11 anaesthetized ventilated dogs. Under control conditions,PO₂ was significantly lower in the subendocardium (13.5±4.5 mm Hg) than in the subepicardium (20.7±2.3 mm Hg), whereasPCO₂ did not differ significantly (43±8.8 and 51±9.2 mm Hg respectively). These variables were not correlated with blood pressure or coronary blood flow. Subendocardial and subepicardialPO₂ decreased less than 5 s after coronary occlusion. These changes were more rapid and severe in the subendocardium. After occlusion for 90 s: subendocardialPO₂ was 4.1±6.3 mm Hg while subepicardialPO₂ was 6.7±15.0 mm Hg (P<0.05).PCO₂ reached peak values of 56±25 mm Hg subendocardial and 82±22 mm Hg subepicardial at 2.67±0.71 min and 3.43±0.93 min after coronary clamping. A reactive hyperemia occurred after coronary unclamping with different time courses and amplitudes for systolic and diastolic stroke flows whilePO₂ recovered with different kinetics. SubendocardialPO₂ increased with a lower initial slope, probably in relation with the delay in the diastolic hyperemia. The observed delayed subendocardial hyperoxia, unrelated to the hyperemia, may indicate a delay in the recovery of normal work and metabolism in the inner layers of the myocardium.     

Distribution of the myocardial tissuePO2 in the rat and the inhomogeneity of the coronary bed

The structural inhomogeneity of the myocardial capillary bed is simulated by microcirculatory units (MCU's) in a diffusion model. This simulation is based on MCU's in which the arrangement of the capillary ends (concurrent structure, partial and total countercurrent structure, helical structure) as well as the structure and supply parameters are varied. The variation of these parameters is based on own measurements of the intracapillary HbO₂ saturation as well as on the following parameters from the literature: frequency distribution of capillary distance and capillary radius, mean capillary length or capillary section length respectively, arterial and mean venousPO₂, mean coronary blood flow, mean O₂ consumption and diffusion conductivity. The analysis of O₂ supply of the normoxic rat heart shows that an O₂ diffusion shunt is obligatory except for MCU's with an extremely large capillary distance or with a concurrent capillary structure. Therefore the minimal tissuePO₂ lies at the level of the capillary venousPO₂ of a MCU. The maximum of the totalPO₂ frequency distribution in the normoxic rat myocardium lies at 25±5 mm Hg, i.e. above the mean venousPO₂ (20 mm Hg). TissuePO₂ values between 0 and 5 mm Hg amount to 0.5%, i.e. they are extremely rare. TissuePO₂ values of 0–1 mm Hg represent less than 0.2%.List of Symbols a arterial capillary end - a branching point of a capillary near the arterial capillary end (branching point of an anastomosis) - A maximal O₂-consumption - A(P) O₂-consumption dependent uponPO₂ - AVDO₂ arterio-venous difference - AVDO₂; AVDO_{2 c} ^(j) arterio-venous difference of a capillary - c _j weighting factor of the capillary distance - c _Hb hemoglobin concentration in the blood - d, d ^j capillary distance - mean capillary distance - i index for the different MCU's (i=1...8) - i.e. PO₂ intracapillaryPO₂ - j index for the parameters of an MCU with the capillary distanced ^(j) (j=1...7) - K diffusion conductivity - l capillary length - l _s capillary section length - MCU microcirculatory unit - P, P(x,y,z), PO₂ O₂ partial pressure - P _a arterialPO₂ - P _a; P_a ^(j) PO₂ at the branching pointa - P _i; P_v ^(j) venousPO₂ - mean venousPO₂ - P ₅₀ PO₂ at half maximal O₂ consumption - P _min,P _min ^(j) minimal tissuePO₂ - r _c, r_c ^(j) capillary radius - mean capillary radius - s(P) relative HbO₂ saturation (HbO₂ dissociation curve) - s ^–1 inverse function of the HbO₂ dissorciation curve - S _v, S_v ^(j) capillary venous HbO₂ saturation - mean venous HbO₂ saturation - v venous capillary end - V volume of the tissue fragment of a MCU - V _c, V_c ^(j) capillary supply volume - W _c, W_c ^(j) blood flow of the supply volume of a capillary (local blood flow) - mean blood flow - x,y,z cartesian coordinates of thePO₂ in a MCU - Bunsen's solubility coefficient - _c . _c ^(J) capilary blood flow - , ^(j) blood flow of an MCU - _i ^(j) (P) relative frequency distribution of thePO₂ in thei-th MCU - (P) relative frequency distribution of thePO₂ of all MCU's, total frequency distribution of the myocardial tissuePO₂ - Laplace operator Supported by the DFG     

APCO2 surface electrode working on the principle of electrical conductivity

APCO₂ electrode working on the principle of electrical conductivity is described. The calibration curve can be linearized according to the formula . This linearity has been tested in thePCO₂ range of 0.93–9.33 kPa (7–70 Torr). For the experiments electrodes are used which have conductivity values of about 50 nS and drifts of maximally 5%/h at aPCO₂ of 5.33 kPa (40 Torr). The response time (T ₉₀) is about 20 s. The temperature sensitivity is 2.4 nS/1 K between 298K–310K. The standard error of the measurements is =0.33 nS. With these electrodes tissuePCO₂ can be measured on the surface of various organs.