Analysis of alveolar PCO 2 control during the menstrual cycle

We attempted to analyze how is regulated during progesterone-induced hyperventilation in the luteal phase. A model for the CO₂ control loop was constructed, in which the function of the CO₂ exchange system was described as and that of the CO₂ sensing system as . Using this model, we estimated (1) the primary increase in produced by progesterone stimulation and (2) the effectiveness (E) of the loop to regulateP _{A CO 2}, defined as P _{A CO 2} (op)/P _{A CO 2} (cl) in which op signifies open-loop and cl, closed-loop. These respiratory variables were investigated throughout the menstrual cycle in 8 healthy women. During the luteal phase, on average, increased by 9.4% andP _{A CO 2},B andH decreased by 0.33 kPa (2.5 mm Hg), 0.47 kPa (3.5 mm Hg) and 13.6%, respectively, whileS and did not change significantly. (op) increased progressively on successive days of the luteal phase whileE remained unchanged at a value of 7.9, thus there was a progressive decrease inP _{A CO 2}. The decrease inH was considered to lessen P _{A CO 2} (op) and so reduce the final deviation ofP _{A CO 2} (P _{A CO 2} (cl)) during the luteal phase. The decrease inB was found to be dependent on (op).     

Effects of acute hypoxia and CO2 inhalation on systemic and peripheral oxygen uptake and circulatory responses during moderate exercise

Summary The effect of acute hypoxia and CO₂ inhalation on leg blood flow (LBF), on leg vascular resistance (LVR) and on oxygen supply to and oxygen consumption in the exercising leg was studied in nine healthy male subjects during moderate one-leg exercise. Each subject exercised for 20 min on a cycle ergometer in four different conditions: normoxia, normoxia +2% CO₂, hypoxia corresponding to an altitude of 4000 m above sea level, and hypoxia +1.2% CO₂. Gas exchange, heart rate (HR), arterial blood pressure, and LBF were measured, and arterial and venous blood samples were analysed for , , oxygen saturation, haematocrit and haemoglobin concentration. Systemic oxygen consumption was 1.83 l · min^–1 (1.48–2.59) and was not affected by hypoxia or CO₂ inhalation in hypoxia. HR was unaffected by CO₂, but increased from 136 beat · min^–1 (111–141) in normoxia to 155 (139–169) in hypoxia. LBF was 6.5 l · min^–1 (5.4–7.6) in normoxia and increased significantly in hypoxia to 8.4 (5.9–10.1). LVR decreased significantly from 2.23 kPa · l^–1 · min (1.89–2.99) in normoxia to 1.89 (1.53–2.52) in hypoxia. The increase in LBF from normoxia to hypoxia correlated significantly with the decrease in LVR. When CO₂ was added in hypoxia a significant correlation was also found between the decrease in LBF and the increase in LVR. In normoxia, the addition of CO₂ caused a significant increase in mean blood pressure. Oxygen consumption in the exercising leg (leg ) in normoxia was 0.97 l · min^–1 (0.72–1.10), and was unaffected by hypoxia and CO₂. It is concluded that the O₂ supply to the exercising leg and its are unaffected by hypoxia and CO₂. The increase in LBF in hypoxia is caused by a decrease in LVR. These changes can be counteracted by CO₂ inhalation. It is proposed that the regulatory mechanism behind these changes is that change in brain causes change in the central regulation of vascular tonus in the muscles.     

CO2 responsivity in the mouse measured by rebreathing

We have modified the rebreathing method to study CO₂ responsivity in very small mammals. Tidal volume (V _T) and frequency (f) of pentobarbital-anesthetized mice were measured during rebreathing from a closed circuit, primed with 95% O₂, 5% CO₂, through which the gas was constantly circulated at 0.5 l·min^–1. The circuit consisted of T-tube from a plethysmograph, Tygon tubing with compliant element, CO₂ analyzer and pump, in series. CircuitPCO₂ (PctCO₂), which was recorded continuously during spontaneous breathing, rapidly equilibrated with end-tidalPCO₂. CO₂ response curves were constructed from extrapolated minute ventilation ( ),V _T,f and parameters of breath-to-breath timing, respectively, onPctCO₂. Analyses of slopes of the response curves, change from onset of rebreathing to peak response, andPctCO₂ at which the response peaked revealed that CO₂ stimulates by increasingf andV _T and that this is effected by facilitation of central inspiratory-expiratory phase switching and inspiratory drive mechanisms. However, the stimulatory effect of CO₂ on phase switching was not sustained, with maximal effect occurring before peak . The advantages and facility of the modified rebreathing method make it suitable for studies of other small mammals, including neonates.     

Ventilatory response of prepubertal boys and adults to carbon dioxide at rest and during exercise

Summary The aim of this study was to determine whether the greater ventilation in children at rest and during exercise is related to a greater CO₂ ventilatory response. The CO₂ ventilatory response was measured in nine prepubertal boys [10.3 years (SD 0.1)] and in 10 adults [24.9 years (SD 0.8)] at rest and during moderate exercise ( CO₂ = 20 ml·kg^–1·min^–1) using the CO₂-rebreathing method. Three criteria were measured in all subjects to assess the ventilatory response to CO₂: the CO₂ sensitivity threshold (Th), which was defined as the value of end titalPCO₂ (P _ETCO₂) where the ventilation increased above its steady-state level; the reactivity slope expressed per unit of body mass (SBM), which was the slope of the linear relation between minute ventilation ( _E) andP _ETCO₂ above Th; and the slope of the relationship between the quotient of tidal volume (V _T) and inspiration time (t _I) andP _ETCO₂ (V _T ·t _I ^–1 ·P _ETCO₂ ^–1) values above Th. The _E,V _T, breathing frequency (f _R), oxygen uptake ( O₂), and CO₂ production ( CO₂) were also measured before the CO₂-rebreathing test. The following results were obtained. First, children had greater ventilation per unit body weight than adults at rest (P<0.001) and during exercise (P<0.01). Second, at rest, onlyV _T ·t _I ^–1 ·P _ETCO₂ ^–1 was greater in children than in adults (P<0.001). Third, during exercise, children had a higher S_BM (P < 0.02) andV _T ·t _I ^–1 ·P _ETCO₂ ^–1 (P<0.001) while Th was lower (P<0.02). Finally, no correlation was found between _E/ CO₂ and Th while a significant correlation existed between _E/ CO₂ and S_BM (adults,r=0.79,P<0.01; children,r=0.73,P<0.05). We conclude that children have, mainly during exercise, a greater sensitivity of the respiratory centres than adult. This greater CO₂ sensitivity could partly explain their higher ventilation during exercise, though greater CO₂ production probably plays a role at rest.     

Bohr effect induced by CO2 and fixed acid at various levels of O2 saturation in duck blood

The Bohr factor, = log /pH, was determined at various levels of hemoglobin O₂ saturation ( ) in fresh whole blood of the duck. Plasma pH was varied by either changing of the blood at constant base excess (CO₂ Bohr factor, ) or by addition of NaHCO₃ and HCl at constant (fixed acid Bohr factor, _AH). No differences were found between and _AH at levels between 20 and 85%, and there was no saturation dependence of the Bohr factor, its average value being –0.44. It is concluded that in whole blood of this bird species CO₂ exerts no direct effect on the O₂ affinity of hemoglobin.     

CO2-ventilatory response of the anesthetized rat by rebreathing technique

The ventilatory response to CO₂ in rats under sodium pentobarbital anesthesia has been measured using the rebreathing technique. The animal rebreathed through a tracheal cannula for a period of 4 min from an apparatus of 200–400 ml capacity, containing 5–6% CO₂ in O₂. in the rebreathing apparatus (PappCO₂), instantaneousV _T,f, and were monitored before, during, and after rebreathing. During the rebreathing run,PappCO₂ andPa _CO2 rose linearly from 35–40 to 65–70 mm Hg; there was no significant difference betweenPappCO₂ andPa _CO2 at any time during rebeathing.V _T and increased almost linearly with the rise inPappCO₂, whilef increased to a maximum within 2 min of rebreathing. In the rat,V _T regulation seemed to operate exclusively as a proportional control system in response to linearly increasing CO₂ stimulus. The slopes ofPappCO₂,V _T or response curves varied considerably during the time course of the experiment, depending upon the level of anesthesia, even though there was no large change in in the control periods which were under hyperoxic conditions. However, a significant linear relationship was seen betweenf in the respective control period and the slope ofPappCO₂-V _T response at various levels of anesthesia. We concluded that the rebreathing technique can be applied in small experimental animals and that changes in the sensitivity of the respiratory control system to a CO₂ stimulus by anesthesia can be easily monitored by repeating the rebreathing test.     

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 involvement of expiratory termination in the vagally mediated facilitation of ventilatory CO2 responsiveness during hyperoxia

In anaesthetized rabbits the influence of differential vagal cold blockade on the ventilatory response to inhaled CO₂ during hyperoxia was investigated.Following total inactivation, the relationship between ventilation ( ) and arterialPCO₂ (P _aCO₂) was shifted to the left and steepened slightly over a range of modest hypercapnia, but was progressively flattened as hypercapnia intensified. The latter effect, suggestive of a vagally mediated facilitation of ventilatory CO₂ responsiveness, was studied further.Differential vagal cold blockade to a temperature (5–11°C) which abolished the Breuer-Hering inflation reflex (end-inspiratory tracheal occlusion no longer eliciting a prolongation of expiratory duration,T _E) had no effect on either during normocapnia or at a substantial level of hypercapnia. Only with further vagal cooling to 0°C did the ventilatory depression during hypercapnia emerge, largely becauseT _E failed to shorten in response to the hypercapnic stimulus.It is concluded that the integrity of expiratory-terminating mechanisms is crucial for the manifestation of the vagally mediated facilitation of and its CO₂ responsiveness which is evident during hyperoxic hypercapnia. A possible role is suggested for lung epithelial irritant receptors or for the tonic late-expiratory activity from pulmonary stretch receptors.Supported by the Deutsche Forschungsgemeinschaft, SFB 114Preliminary reports of this work have been presented in Pflügers Arch 355: (Suppl) R47 (1975); 377: (Suppl) R54 (1978) and in Proc. XXVIII. Int. Congr. of Physiol. Sciences, Budapest, Vol VIV, 515 (1980)     

Bio-energetic profile in 144 boys aged from 6 to 15 years with special reference to sexual maturation

Summary The effects of growth and pubertal development on bio-energetic characteristics were studied in boys aged 6–15 years (n = 144; transverse study). Maximal oxygen consumption (VO_2max, direct method), mechanical power at (VO_2max ( ), maximal anaerobic power (P_max; force-velocity test), mean power in 30-s sprint (P _30s; Wingate test) were evaluated and the ratios between P_max,P _30s and were calculated. Sexual maturation was determined using salivary testosterone as an objective indicator. Normalized for body massVO_2max remained constant from 6 to 15 years (49 ml· min^–1 · kg^–1, SD 6), whilst P_max andP _30s increased from 6–8 to 14–15 years, from 6.2 W · kg^–1, SD 1.1 to 10.8 W · kg^–1, SD 1.4 and from 4.7 W · kg^–1, SD 1.0 to 7.6 W · kg^–1, SD 1.0, respectively, (P < 0.001). The ratio P_max: was 1.7 SD 3.0 at 6–8 years and reached 2.8 SD 0.5 at 14–15 years and the ratioP _30s: changed similarly from 1.3 SD 0.3 to 1.9 SD 0.3. In contrast, the ratio P_max:P _30s remained unchanged (1.4 SD 0.2). Significant relationships (P < 0.001) were observed between P_max (W · kg^–1),P _30s (W · kg^–1), blood lactate concentrations after the Wingate test, and age, height, mass and salivary testosterone concentration. This indicates that growth and maturation have together an important role in the development of anaerobic metabolism.     

A method for estimating bicarbonate buffering of lactic acid during constant work rate exercise

A method to estimate the CO₂ derived from buffering lactic acid by HCO₃ ^– during constant work rate exercise is described. It utilizes the simultaneous continuous measurement of O₂ uptake ( O₂) and CO₂ output ( CO₂), and the muscle respiratory quotient (RQ_m). The CO₂ generated from aerobic metabolism of the contracting skeletal muscles was estimated from the product of the exercise-induced increase in O₂ and RQ_m calculated from gas exchange. By starting exercise from unloaded cycling, the increase in CO₂ stores, not accompanied by a simultaneous decrease in O₂ stores, was minimized. The total CO₂ and aerobic CO₂ outputs and, by difference, the millimoles (mmol) of lactate buffered by HCO₃ ^– (corrected for hyperventilation) were estimated. To test this method, ten normal subjects performed cycling exercise at each of two work rates for 6 min, one below the lactic acidosis threshold (LAT) (50 W for all subjects), and the other above the LAT, midway between LAT and peak O₂ [mean (SD), 144 (48) W]. Hyperventilation had a small effect on the calculation of mmol lactate buffered by HCO₃ ^– [6.5 (2.3)% at 6 min in four subjects who hyperventilated]. The mmol of buffer CO₂ at 6 min of exercise was highly correlated (r = 0.925, P < 0.001) with the increase in venous blood lactate sampled 2 min into recovery (coefficient of variation = ±0.9 mmol·l^–1). The reproducibility between tests done on different days was good. We conclude that the rate of release of CO₂2 from HCO₃ ^– can be estimated from the continuous analysis of simultaneously measured CO₂, O₂, and an estimate of muscle substrate.     

Physiological responses to intermittent and continuous exercise at the same relative intensity in older men

We investigated the physiological responses in older men to continuous (CEx) and intermittent (IEx) exercise. Nine men [70.4 (1.2) years, O_2peak: 2.21 (0.20) l min^–1; mean (SE)] completed eight exercise tests (two CEx and six IEx) on an electronically braked cycle ergometer in random order. CEx and IEx were performed at 50% and 70% O_2peak. IEx was performed using 60sE:60sR, 30sE:30sR and 15sE:15sR exercise to rest ratios. The duration of exercise was adjusted so that the total amount of work completed was the same for each exercise test. Oxygen uptake (O₂), minute ventilation (_E) and heart rate (HR) were measured at the mid-point of each exercise test. Arterialised blood samples were obtained at rest and during exercise and analysed for pH and PCO₂. At the same relative intensity (50% or 70% O_2peak), IEx resulted in a significantly lower (P<0.01) O₂, _E and HR than CEx. There were no significant differences (P>0.05) in O₂, _E and HR measured at the mid point of the three exercise to rest ratios at 50% and 70% O_2peak. pH and PCO₂ during CEx and IEx at 50% O_2peak were not significantly different from rest. CEx performed at 70% O_2peak resulted in significant decreases (P<0.05) in pH and PCO₂. There was a significant decrease (P<0.05) in pH only during the 60sE:60sR IEx at 70% O_2peak. Changes in arterialised PCO₂ during the 60sE:60sR, 30sE:30sR and 15sE:15sR at both 50% and 70% O_2peak exercise tests were not significant. When exercising at the same percentage of O_2peak and with the total amount of work fixed, IEx results in significantly lower physiological responses than CEx in older men. All results are given as mean (SE).     

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     

Adaptive changes in hypercapnic ventilatory response during training and detraining

Summary To confirm the effects of physical training and detraining on CO2 chemosensitivity, we followed hypercapnic ventilatory response at rest in the same five subjects during pre-, post- and detraining for 6 years. They joined our university badminton teams as freshmen and participated regularly in their team's training for about 3 h a day, three times a week, for 4 years. After that they retired from their teams and stopped training in order to study in the graduate school for 2 years. Maximum pulmonary ventilation and maximal oxygen uptake for each subject were determined during maximal treadmill exercise. The slope (S) of ventilatory response to carbon dioxide at rest was measured by Read's rebreathing method. Mean values of increased statistically during training and decreased statistically during detraining. A similar tendency was observed in . The average value ofS before training was 1.91 l·min^–1·mmHg^–1, (+) SD 0.52 and it decreased gradually with increasing training periods; the difference between theS values before (1980) and after training (1982, 1983 and 1984) were all significant. Furthermore, the mean values ofS increased significantly during detraining as compared with those obtained at the end of training (April 1984). We concluded that in normal subjects, long-term physical training increases aerobic work capacity and decreases CO₂ventilatory responsiveness, and that the ventilatory adaptations with training observed here are reversible through detraining.     

Cardiac output during exercise in paraplegic subjects

Summary The purpose of this study was to measure the cardiac output using the CO₂ rebreathing method during submaximal and maximal arm cranking exercise in six male paraplegic subjects with a high level of spinal cord injury (HP). They were compared with eight able bodied subjects (AB) who were not trained in arm exercise. Maximal O₂ consumption ( O_2max) was lower in HP (1.1 1·min^–1, SD 0.1; 17.5 ml·min^–·kg, SD 4) than in AB (2.5 1·min^–1, SD 0.6; 36.7 ml·min^–1·kg, SD 10.7). Maximal cardiac output was similar in the groups (HP, 141·min^–1 SD 2.6; AB, 16.81·min^–1 SD 4). The same result was obtained for maximal heart rate (f _c,max (HP, 175 beats·min^–1, SD 18; AB, 187 beats·min^–, SD 16) and the maximal stroke volume (HP, 82 ml, SD 13; AB, 91 ml, SD 27). The slopes of the relationshipf _c/ O₂ were higher in HP than AB (P<0.025) but when expressed as a % O_2max there were no differences. The results suggests a major alteration of oxygen transport capacity to active muscle mass in paraplegics due to changes in vasomotor regulation below the level of the lesion.     

Reliability of the cardiac output measurement with the indirect Fick-principle for CO2 during exercise

Cardiac output measurements were performed during 50 exercise tests in 16 normal subjects employing the indirect Fick principle for CO₂. During sub-maximal steady state exercise the plateau CO₂ tension ( ) was estimated with a rebreathing procedure. The mixed venous CO₂ tension ( ) was calculated by subtracting the alveolocapillary CO₂ tension difference from the . Compared with data from the literature the most valid calculation of the cardiac output was obtained by using the . Cardiac output values, calculated via the turned out to be too low.The reproducibility was tested by repitition of 18 exercise tests at least after 5 days. The relative standard error of a single observation was 4.1% for the cardiac output, which was found to be as good as that of invasive measurements.     

Fast measurement of the CO2 partial pressure in gases and fluids

A CO₂-electrode system consisting of a membrane covered pH electrode, an electronic antilog modul and a special electronic analog circuit is described. Since the electrode output signal is a logarithmic function of the CO₂ partial pressure the output signal of the antilog module is proportional to the CO₂ partial pressure. The time course of the electrode signal has been analyzed after a step change of . This step response may be approximated by a sum of three exponential functions. Knowing the dynamic behaviour, the transfer function is formulated mathematically and a special analog circuit is constructed with a frequency response inverse to the frequency response of the electrode. Using this device the response time (T ₉₅) of the electrode system is diminished from 11,5 s to 750 ms after a step change of in gas (Luttmann, et al., 1974). If the time for the hydration of CO₂ is decreased by the addition of carbonic anhydrase the response time of the electrode is diminished to 6.5 s. Using the analog circuit yields a response time of 200 ms.Further studies were made to analyze the transient response in fluids at various flow velocities and various mountings. In order to analyze the influence of the fluid boundary layer on the surface of the electrode a photometric method has been developed (Luttmann and Mückenhoff, 1975), which allows to estimate the time course of the CO₂ partial pressure independently of and simultaneously with the electrode measurement.The experimental data are compared with a theory based on theoretical considerations of Schuler and Kreuzer (1967) and Crank (1956).List of Symbols A _i gain factor of thei-th compartment - A _i gain factor of the simulation network - C _i capacity - D diffusion coefficient - d electrode diameter - fraction of CO₂ - F _c (j) frequency response of the linearizing network - F _g (j) frequency response of the boundary layer - F _M (j) frequency response of the measuring system - F _M frequency response of the simulation network - I _i impedance transformer - j Gauss number (j ²=–1) - (j) frequency function of the CO₂ partial pressure - (t) time function of the CO₂ partial pressure - R _i electrical resistance - T _i time constant of the electrode - T _i time constant of the simulation network - T ₉₅ time for reaching 95% of the total difference - V voltage gain factor - v velocity of the streaming fluid - x coordinate - x(t) time function - X(j) corresponding frequency function - dilution factor - inverse time constant - thickness of boundary layer - ^* kinematic viscosity - thickness of diffusion layer - radian frequency Supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 114 (Bionach)     

Respiratory gas exchange indices used to detect the blood lactate accumulation threshold during an incremental exercise test in young athletes

Summary The time course of changes in blood lactate concentration and ventilatory gas exchange was studied during an incremental exercise test on a cycle ergometer to determine if the lactate accumulation threshold (LT₂) could be accurately estimated by the use of respiratory indices (VT₂) in young athletes. LT₂ was defined as the starting point of accelerated lactate accumulation. VT₂ was identified by the second exponential increase in _E and the ventilatory equivalent for O₂ uptake with a concomitant nonlinear increase in the ventilatory equivalent for CO₂ output. Twelve trained subjects, aged 18–22 years, participated in this study. The initial power setting was 30 W for 3 min with successive increases of 30 W every minute except at the end of the test when the increase was reduced. Ventilatory flow ( _E), oxygen uptake ( O₂), carbon dioxide output ( CO₂), and ventilatory equivalents of O₂ and CO₂ were determined during the last 30 s of every minute. Venous blood samples were drawn at the end of each stage of effort and analysed enzymatically for lactate concentration. After each test, LT₂ and VT₂ were determined visually by two investigators from the graphic results using a double-blind procedure. The results [mean (SEM)] indicate no significant difference between LT₂ and VT₂ expressed as O₂ [43.98 (1.70) vs 44.93 (2.39) ml - min^– - kg^–], lactataemia [4.01 (0.28) vs 4.44 (0.37) mM - 1^–], or heart rate [171 (3.36) vs 173 (3.11) min^–]. In addition, strong correlations were noted between the two methods for O₂ (r=0.90,P<0.001), lactataemia (r=0.75,P<0.01), and heart rate (r=0.96,P<0.001). It is concluded that VT₂ coincides with LT₂ determination and that the ventilatory gas exchange method can thus satisfactorily evaluate the lactate accumulation threshold in young athletes.     

Effect of an increase in{\text{Hb}}_{{\text{O}}_{\text{2}} } affinity on the calculated capillary recruitment of an isolated rat heart

The effect of an increase in hemoglobin O₂ affinity on myocardial O₂ delivery was studied in a blood perfused working rat heart preparation. In a first series of experiments P₅₀ ( for which saturation is 50%) was lowered by use of carbon monoxide. The heart was alternatively perfused with the blood sample of P₅₀=32 mm Hg and the blood sample of P₅₀=17 mm Hg. O₂ capacity of both samples was kept the same by appropriate hemodilution. In a second serie of experiments change of P₅₀ was obtained by the use of adult human erythrocytes containing hemoglobin creteil with a P₅₀ of 13.6 mm Hg. As P₅₀ decreased from 25 to 10 mm Hg, coronary sinus ( ) diminished from 26±2 to 18±2 mm Hg (–29±2%), coronary sinus O₂ content ( ) increased by 15±3%, myocardial oxygen consumption did not change significantly. The percentage of increase of coronary flow was 23±4%.Analysis of these results with a simple mathematical model of O₂ delivery suggest that increase in affinity is corrected by a simultaneous increase in coronary flow and capillary recruitment.This study was supported by contracts 74-7-0274 from D.G.R.S.T., 76-1-1755 from I.N.S.E.R.M. and a grant from the University of Paris VII     

Ventilatory effects of hypercapnic end-tidalPCO2 clamps during aerobic exercise of varying intensity

Summary Nine subjects performed a sequence of sustained and randomised changes between 40 W and 100 W on a cycle ergometer while the end-tidal was kept close to 17.3 kPa (130 mm Hg) by means of a dynamic forcing technique (reference experiment). In a second series inspiratory CO₂ was additionally manipulated so as to hold end-tidal (P _ETCO₂) near 6.5 kPa (49 mm Hg; CO₂-clamp experiment). By this forcingP _ETCO₂ oscillations were attenuated and more evenly distributed over the frequency range. Ventilation ( ) responded to this manoeuvre with an upward trend that could not be ascribed to a slow CO₂-response component, changes in metabolic rate or a dissociation of end-tidal and arterial . differences between reference and CO₂-clamp experiments were abolished within a 3-min period following the termination of the external CO₂ control. The present results suggest that the CO₂-H⁺ stimulus plays a major role in adjusting ventilation when exercise intensity is decreased. The underlying CO₂ effect appears to be neither additive nor bi-directionally symmetrical.     

Interstitial PCO2 and pH in rat hippocampal slices measured by means of a novel fast CO2/H+-sensitive microelectrode based on a PVC-gelled membrane

We describe here the construction and properties of a double-barrelled microelectrode (tip diameter 4–10 m) which permits simultaneous measurements of PCO₂ and pH, and which has a 90% response time of only one or a few seconds for a step change in PCO₂. The fast response of the CO₂-sensitive barrel is due to (i) the use of a PVC-gelled (tridodecylamine-containing) membrane solution which enables the construction of extremely short ( 4 m), yet mechanically stable, membrane columns, and (ii) the presence of carbonic anhydrase in the filling solution. Recordings made in the pyramidal layer of area CA1 in rat hippocampal slices showed that the deviation in the acid direction of the basal interstitial pH (pH₀) from that of the perfusion solution was attributable to a higher PCO₂ level within the tissue. Most of the late acid shift evoked by stimulation of the Schaffer collaterals (5- to 20-s trains at 10 Hz) could also be explained on the basis of an accumulation of interstitial CO₂ at a constant HCO ₃ ^– concentration. This conclusion was supported by the finding that inhibition of extracellular carbonic anhydrase activity by 10 M benzolamide completely abolished the activity-induced fall in pH₀, but not the increase in PCO₂. The initial stimulus-induced alkalosis was accompanied by a slight decrease in PCO₂ only, implying a parallel increase in the interstitial HCO ₃ ^– concentration. Benzolamide produced a dramatic enhancement of the early alkaline shift as well as of the simultaneous fall in PCO₂. The latter effect of the drug unmasks a cellular CO₂ sink that is induced by neuronal activity.