Blood gases at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve

Theoretical deductions have shown that a shift of the blood O₂ dissociation curve (ODC) to the right might improve O₂ transport to tissues at normoxia and at mild hypoxia whereas at severe hypoxia the organism should be better off with an ODC shifted to the left (Turek et al., 1973b; Turek and Kreuzer, 1976). The present study was performed in order to ascertain this ambiguous effect of an ODC shift depending on the degree of hypoxia in intact animals. A major displacement of the ODC to the left was achieved in rats by chronic administration of sodium cyanate (NaOCN). Control animals received sodium chloride (NaCl) instead. Arterial and mixed-venous , , and pH were measured at normoxia and during breathing 14.9, 8.0, or 5.6% O₂ in N₂ in both groups. From , pH, ODC and arterial hematocrit, arterial and mixed-venous O₂ contents were estimated and as an index of blood O₂ extraction was obtained. At normoxia and during breathing 14.9% O₂ the NaOCN rats had a lower mixed-venous than the NaCl rats without any difference in pH. Arterio-venous O₂ difference did not differ at normoxia but was lower in NaOCN rats at 14.9% O₂. However, at 8.0 and 5.6% O₂ the NaOCN rats had a higher mixed-venous , an increased , and a higher pH (arterial and mixed-venous). At 5.6% O₂ the NaCl rats developed a severe acidosis concomitant with pronounced hypocapnia. These findings confirm that rats with a left-shifted ODC have an impaired O₂ transport to tissues at normoxia and mild hypoxia but a more efficient O₂ transport at severe hypoxia as compared with rats with an unshifted ODC, in agreement with our previous theoretical studies.Preliminary communications of part of this material at the FASEB Meeting in Anaheim, California, on April 11–16, 1976 (Fed. Proc.35, 526, 1976), and at the Dutch Federation Meeting in Amsterdam on April 21–23, 1976 (Volume of Abstracts, p. 381)     

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.     

Precision of ventilatory and gas exchange alterations as a predictor of the anaerobic threshold

Summary Anaerobic threshold has been defined as the oxygen uptake ( ) at which blood lactate (La) begins to rise systematically during graded exercise (Davis et al. 1982). It has become common practice in the literature to estimate the anaerobic threshold by using ventilatory and/or gas exchange alterations. However, confusion exists as to the validity of this practice. The purpose of this study was to examine the precision with which ventilatory and gas exchange techniques for determining anaerobic threshold predicted the anaerobic threshold resolved by La criteria. The anaerobic threshold was chosen using three criteria: (1) systematic increase in blood La (AT_La), (2) systematic increase in ventilatory equivalent for O₂ with no change in the ventilatory equivalent for CO₂ ( ), and (3) non-linear increase in expired ventilation graphed as a function of ( ). Thirteen trained male subjects performed an incremental cycle ergometer test to exhaustion in which the load was increased by 30 W every 3 minutes. Ventilation, gas exchange measures, and blood samples for La analysis were obtained every 3rd min throughout the test. In five of the thirteen subjects tested the anaerobic threshold determined by ventilatory and gas exchange alterations did not occur at the same as the AT_La. The highest correlation between a gas exchange anaerobic threshold and AT_La was found for and was r=0.63 (P<0.05). These data provide evidence that the AT_La and do not always occur simultaneously and suggest limitations in using ventilatory or gas exchange measures to estimate the AT_la.     

Age predicts cardiovascular,but not thermoregulatory,responses to humid heat stress

Cross-section comparisons of the effect of age on physiological responses to heat stress have yielded conflicting results, in part because of the inability to separate chronological age from factors which change in concert with the biological aging process. The present study was designed to examine the relative influence of age on cardiovascular and thermoregulatory responses to low intensity cycle exercise (60 W for 1 h) in a warm humid environment (35°C, 80% relative humidity). Specifically, the relative importance of age compared to other individual characteristics [maximal oxygen uptake ( _max), physical activity level, anthropometry, and adiposity] was determined by multiple regression analysis in a heterogeneous sample of 56 subjects in which age (20–73 years) and _max (1.864–44 l · min^–1) were not interrelated. Dependent variables (with ranges) included final values of thermoregulatory responses [rectal temperature (T _re, 37.8–39.2°C), calculated heat storage (S, 3.4–8.1 J · g^–1), sweat loss (238–847 g · m^–2)] and cardiovascular responses [heart rate (HR, 94–176 beats min^–1), forearm blood flow (FBF, 5.3–31.3 ml · 100 ml^–1 · min^–1), mean arterial blood pressure (MAP, 68–122 mmHg), and forearm vascular conductance (FVC = FBF · MAP^–1, 0.06–0.44 ml · 100 ml^–1 · min^–1 · mmHg^–1). Age had no significant influence onT _re,S, or sweat loss, all of which were closely related to _max. On the other hand, HR, MAP, FBF, and FVC were related to both age and _max. Anthropometric variables and adiposity had secondary, but statistically significant, effects on MAP, FBF, FVC, and sweat loss. With respect to exercise in a warm humid environment, it was concluded that the effect of age on body temperature and sweating was negligible compared to effects related to _max, but that chronological age had an independent effect on cardiovascular effector responses.     

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.     

Cardiorespiratory and metabolic adaptations to hyperoxic training

This study examined the effects of hyperoxic training on specific cardiorespiratory and metabolic responses. A group of 19 male subjects trained for 5 weeks on a cycle ergometer at 70% of hyperoxic or normoxic maximal heart rate, the hyperoxic group (HG) breathing 70% O₂, the normoxic group (NG) breathing 21% O₂. The subjects were tested pre- and post-training under both hyperoxia and normoxia. Measurements included cardiac output , stroke volume (SV), heart rate (HR), pulmonary ventilation , oxygen consumption , partial pressure of oxygen (PO₂), partial pressure of inspired carbon dioxide (PCO₂), blood lactate concentration [L], and fiber type composition. The was significantly lower at submaximal work rates (P < 0.05) and maximal increased after training in both groups for both test conditions; hyperoxic was lower than normoxic (P < 0.05). The maximal increased significantly (P < 0.05) in both groups for both tests and was 11%–12% higher during hyperoxia. Post-training maximal heart rate (HR_max) was significantly decreased (P < 0.05) at the same absolute work rate regardless of the training group or test type. The SV was increased at each work rate and was unchanged. The maximal increased significantly (P < 0.05) for both groups and types of test: for normoxia: NG 27.3–30.4 l · min^–1 and HG 30.3–32.31 · min^–1 and for hyperoxia: NG 24.7–25.6 and HG 27.9–31.2 l · min^–1. Although working at the same intensity relative to HR_max, HG showed significantly lower [L] following a single training session, yet maximal values were unchanged after training. Both groups showed a significant increase in the percentage of type IIA fibers post-training but HG retained a larger percentage of HB fibers. Mitochondrial enzymes; citrate kinase, 3-hydroxyacyl CoA dehydrogenase, and cytochrome c-oxidase were increased in the normoxic trained subjects (P < 0.05). In summary, training induced adaptive responses in maximal aerobic power, HR, SV, , [L], and muscle fiber type composition, independent of inspired PO₂. Intramuscular data suggested there may be some differences between hyperoxic and normoxic training and these were substantiated by mitochondrial enzyme and lactate findings. Our data would suggest that transport mechanisms may limit the ability to increase aerobic power.     

The energy cost of level cross-country skiing and the effect of the friction of the ski

Summary Oxygen consumption [( ) in ml·kg^–1·min^–1], blood lactate concentration ([La] in mM) and dynamic friction of the skis on snow [(F) inN] were measured in six athletes skiing on a level track at different speeds [(v) in m·min^–1] and using different methods of propulsion. The increased withv andF, the latter depending mostly on snow temperature, as did [La]. The was very much affected by the skiing technique. Multiple regression equations gave the following results: with diagonal stride (DS), =–23.09+0.189v+0.62N; with double pole (DP), =–30.95+0.192v+0.51N; and with the new skating technique (S), =–32.63 +0.171+0.68N. In terms of DS is the most expensive technique, while S is the least expensive; however, asF increases, S, at the highest speed, tends to cost as much as DP. At speeds from 18 to 22 km·h^–1, the speeds measured in the competitions, theF for DS and DP can represent from 10% to 50% of the energy expenditure, withF ranging from 10 to 60N; with S this range increases to 20%–70%. This seems to depend on the interface between the skis and the snow and on the different ways the poles are used.     

Role of O2 in Regulation of Lactate Dynamics during Hypoxia: Mathematical Model and Analysis

The mechanistic basis of the relationship between O₂ and lactate concentration in muscle is not fully understood. Although hypoxia can cause lactate (LA) accumulation, it is possible for LA accumulation to occur without hypoxia. Nevertheless, during conditions of low O₂ availability, blood and tissue LA accumulation are used as indicators of hypoxia. To provide a framework for analyzing changes in energy metabolism and its regulation, we developed a mathematical model of human bioenergetics that links cellular metabolic processes to whole-body responses. Our model is based on dynamic mass balances and mechanistic kinetics in muscle, splanchnic and other body tissues for many substrates (glycogen, glucose, pyruvate, LA, O₂, CO₂, etc.) and control metabolites (e.g., ATP) through coupled reaction processes. Normal substrate concentrations in blood and tissues as well as model parameters are obtained directly or estimated indirectly from physiological observation in the literature. The model equations are solved numerically to simulate substrate concentration changes in tissues in response to disturbances. One key objective is to examine and quantify the mechanisms that control LA accumulation when O₂ availability to the muscle is lowered. Another objective is to quantify the contribution of different tissues to an observed increase in blood lactate concentration. Simulations of system responses to respiratory hypoxia were examined and compared to physiological observations. Model simulations show patterns of change for substrates and control metabolites that behave similarly to those found experimentally. From the simulations, it is evident that a large decrease can occur in muscle O₂ concentration, without affecting muscle respiration ( ) significantly. However, a small decrease in (1%–2%) can result in a large increase in LA production (50%–100%). The cellular rate of oxygen consumption, , which is coupled to ATP formation and NADH oxidation, can regulate other processes (e.g., glycolysis, pyruvate reduction) with high sensitivity through its effects on ADP/ATP and NADH/NAD. Thus, although LA metabolism does not depend directly on O₂ concentration, it is indirectly affected by , through changes in ADP/ATP, and NADH/NAD. Arterial LA concentration (C_a,LA) follows the pattern of change of muscle LA concentration (C_m,LA). Nevertheless, changes in C_a,LA, due to C_m,LA, are unlikely to be detected experimentally because changes in C_m,LA are small relative to the total LA concentrations in other tissues. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 8722Fy     

Effects of previous exercise on the ventilatory determination of the aerobic threshold

Summary To study the effects of previous submaximal exercise on the ventilatory determination of the Aerobic Threshold (AeT), 16 men were subjected to three maximal exercise tests (standard test = ST, retest = RT, and test with previous exercise = TPE) on a cycle ergometer. The protocol for the three tests consisted of 3 min pedalling against 25 W, followed by increments of 25 W every minute until volitional fatigue. TPE was preceded by 10 min cycling at a power output corresponding to the AeT as determined in ST, followed by a recovery period pedalling against 25 W until returned to values consistent with the initial response to 25 W. AeT was determined from the gas exchange curves (ventilatory equivalent for O₂, fraction of expired O₂, excess of , ventilation, and respiratory gas exchange ratio) printed every 30 s. The results showed good ST×RT reliability (r=0.89). TPE showed significantly higher AeT values (2.548±0.44 l·min^–1) when compared with ST (2.049±0.33 l·min^–1) and RT (2.083±0.30 l·min^–1). There were no significant differences for the sub-threshold respiratory gas exchange ratios among the trials. The sub-threshold response showed significantly higher values for TPE at power outputs above 50 W. It was concluded that the performance of previous exercise can increase the value for the ventilatory determination of the AeT due to a faster sub-threshold response.Supported by fellowship number 3660/80-3, CAPES, Brazil     

Physical work capacity in dynamic exercise with differing muscle masses in healthy young and older men

Ten young (aged 23–30 years) and nine older (aged 54–59 years) healthy men with similar estimated limb muscle volumes performed, in random order, three different types of ergometer exercise tests (one-arm cranking, two-arm cranking, and two-leg cycling) up to the maximal level. Values for work load (WL), peak oxygen consumption , peak heart rate (HR), peak ventilation , respiratory gas exchange ratio (R), recovery blood lactate concentration [La^–], and rating of perceived exertion (RPE) were compared between the age-groups in the given exercise modes. No significant age-related differences in WL, peak , peak HR, R, [La^–], or RPE were found in one-arm or two-arm cranking. During one-arm cranking the mean peak was 1.65 (SD 0.26)1 · min^–1 among the young men and 1.63 (SD 0.10)1 · min^–1 among the older men. Corresponding mean peak during two-arm cranking was 2.19 (SD 0.32)1 · min-1 and 2.09 (SD 0.18)1 · min^–1, respectively. During one-arm cranking peak was higher (P < 0.05) among the older men compared to the young men. During two-leg cycling the young men showed higher values in WL (P < 0.001), peak (P < 0.001), and peak HR (P < 0.001). The mean peak was 3.54 (SD 0.24)1 · min^–1 among the young men and 3.02 (SD 0.20)1 · min^–1 among the older men. Corresponding mean peak HR was 182 (SD 5) beats · min^–1 and 170 (SD 8) beats · min^–1, respectively. During two-leg cycling, peak , R, [La^–], and RPE did not differ between the two age-groups. In summary, the older men with similar sizes of estimated arm and leg muscle volumes as the young men had a reduced physical work capacity in two-leg cycling. In one-arm or two-arm cranking, no significant difference in work capacity was found between the age-groups. These results indicate, that in healthy men, age, at least up to the 6th decade of life, is not necessarily associated with a decline in physical work capacity in exercises using relatively small muscle groups, in which the limiting factors are more peripheral than central.     

Times to exhaustion at 100% of velocity at\dot V{\text{O}}_{\text{2}} max and modelling of the time-limit / velocity relationship in elite long-distance runners

The aim of this study was to measure running times to exhaustion (Tlim) on a treadmill at 100% of the minimum velocity which elicits _{max max} in 38 elite male long - distance runners _max = 71.4 ± 5.5 ml.kg^–1.min^–1 and _max = 21.8 ± 1.2 km.h^–1). The lactate threshold (LT) was defined as a starting point of accelerated lactate accumulation around 4 mM and was expressed in _max. Tlim value was negatively correlated with _max (r = -0.362, p< 0.05) and _max (r = –0.347, p< 0.05) but positively with LT (%v _max) (r = 0.378, p < 0.05). These data demonstrate that running time to exhaustion at _max in a homogeneous group of elite male long-distance runners was inversely related to _max and experimentally illustrates the model of Monod and Scherrer regarding the time limit-velocity relationship adapted from local exercise for running by Hughson et al. (1984) .     

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     

Renal hemodynamics and renal O2 uptake during hypoxia in the anesthetized rabbit

Summary The effects of hypoxic hypoxia on renal hemodynamics and metabolism have been studied in anaesthetized mechanically ventilated rabbits. Acute hypoxia (F₁O₂=0.10,PaO₂=35 torr) induces at constant mean arterial pressure a 45% decrease in RBF, GFR, and whereas free water clearance increases. These alterations were still apparent 50 min after resuming normal arterial oxygenation. In order to assess the role of the stimulation of catecholamine release in these observations, two other sets of experiments were performed: 1) the animals were ventilated with the same hypoxic gas mixture but after adrenergic blockade (phentolamine: 0.2 mg·kg·min^–1 i.v.), 2) hypoxia was induced by ventilating the animals with CO (F_ICO=0.002) at constantPaO₂. Increase in renal vascular resistance and reduction of renal O₂ uptake were still observed. This indicates that adrenergic stimulation cannot fully explain the renal vasoconstriction encountered in hypoxia. The role of a local vasoactive factor, especially that of the renin angiotensin system is discussed. The apparent O₂ cost of Na reabsorption was not greatly modified by any type of hypoxia and the Na:O₂ ratio remained close to the value observed in normoxic animals. This indicates that the kidney may adapt to hypoxia by reducing its O₂ demand keeping unaltered its tubular function and basal O₂ needs.     

Le métabolisme non lié à l'activité musculaire est fonction de {\text{FA}}_{{\text{CO}}_{\text{2}} } et de la température

Summary Metabolic variations as a function of and as a function of temperature are studied in curarized, artificially ventilated cats. Metabolic rate is measured in terms of O₂ uptake and CO₂ production. Measures are taken for variations of 4–7% and for temperatures between 42 and 21°C. The results are presented in the form of graphs. Metabolism decreases when increases and increases when temperature increases. The shape of the curve obtained when values for metabolic rate are plotted as a function of temperature, depends upon the ventilation which acts by determining the magnitude of .     

Physical fitness of blind and sighted children

Summary Twenty-seven children (age 7–17 years) with varying degrees of blindness but with no other known disorder were assessed for physical fitness. Twenty-seven randomly selected children with normal eyesight were also assessed. Maximum oxygen uptake ( ) was measured directly during a progressive exercise test on a treadmill. There was a significant and substantial reduction in in totally blind children (mean ± standard deviation 35.0±7.5 ml · min^–1 · kg^–1) compared with normal children (45.9±6.6 ml · min^–1 · kg^–1). Partially sighted children had a significant but smaller reduction in . Fitness assessed by a step-test was significantly reduced in the visually impaired children, and skin-fold thickness was also significantly greater in totally blind children.The level of habitual physical activity for each child, as assessed by a questionnaire, correlated with (r=0.53,p<0.0001). Blind children were significantly less active than normal children, and the difference between mean for blind and normal children became non-significant when their different activity levels were taken into account. It is concluded that totally blind children are less fit than other children at least partly because of their lower level of habitual activity.     

Improved estimation of total oxygen uptake in exercise by evaluation of aerobic fitness

Summary The purpose of the present study was to contrive a new practical method for estimating total O₂ uptake during exercise from total heart beats after individual evaluation of aerobic fitness levels. Twenty healthy male subjects participated in cycle ergometer tests, maximal O₂ uptake ( ) tests and various simple tests including simple endurance tests. From the cycle ergometer results, the following formula for estimating total O₂ uptake in exercise was determined: (ml·kg^–1)=SR₁₂₅×(45.8× mean HR+4268)×THB×10^–4 where , THB, and mean HR are total O₂ uptake, total heart beats, and mean heart rate (beats · min_–1) in exercise, respectively, and SR₁₂₅ is the slope of the regression line between accumulated heart beats and accumulated O₂ uptake during exercise at 125 beats · min^–1 of mean HR. SR₁₂₅ had a significant correlation not only with but also with each score (X) in any simple endurance tests such as, for example, a step test for 2 min. In this case, accordingly, SR₁₂₅ can be found as; SR₁₂₅=–0.00118X+0.3478. These formulae indicate that the total O₂ uptake of any exercising subject can be estimated from his total heart beats regardless of intensities of exercise when his aerobic fitness level is evaluated by the simple endurance test. The total O₂ uptake estimated by our method was compared to that measured by the Douglas bag method, and the discrepancy between the two results was less than the errors of values estimated by traditional methods.Supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (grant no. 57780095)     

Cardiorespiratory effects of respiratory protective devices during exercise in well-trained men

Summary The effects of a filtering device, an air-line breathing apparatus and a self-contained breathing apparatus (SCBA) on pulmonary ventilation, oxygen consumption and heart rate were studied in 12 well-trained firemen aged 21–35 years. Their average maximal oxygen consumption ( max) was 64.9 ml·min^–1·kg^–1. Sequential tests without and with the respirator were performed on a treadmill. The continuous test contained five components, each of which lasted 5 min: sitting at rest, walking at 20%, 40%, and 60% of the individual max, and recovery sitting. During the higher submaximal work levels and recovery, ventilation, heart rate, and oxygen consumption in particular increased more with respirators than without them. At the highest work level the increments in oxygen consumption caused by the respirators were 13%, (8.7 ml·min^–1·kg^–1), 7% (4.4 ml·min^–1·kg^–1), and 20% (12.7 ml·min^–1·kg^–1) of max. All three respirators hampered respiration, resulting in hypoventilation. The additional effort of breathing and the weight of the apparatus (15 kg with the SCBA) increased the subjects' cardiorespiratory strain so clearly that the need for rest periods and the individual's work capacity when the respirators are worn must be carefully considered, particularly with the SCBA.     

O2–Hb Reaction Kinetics and the Fåhraeus Effect during Stagnant, Hypoxic, and Anemic Supply Deficit

We modified our previous computer model of O₂ and CO₂ transport in the cerebral microcirculation to include nonequilibrium O₂–Hb kinetics and the Fåhraeus effect (reduced tube hematocrit in small microvessels). The model is a steady-state multicompartmental simulation which includes three arteriolar compartments, three venular compartments, and one capillary compartment. Three different types of oxygen deficits (stagnant, hypoxic, and anemic conditions) were simulated by respectively reducing blood flow, arterial O₂ saturation, and systemic hematocrit to one half of normal. Microcirculatory distributions for O₂ saturation and deviations from equilibrium, and the O₂ and CO₂ fluxes for each compartment were predicted for the three O₂ supply deficits. Differences were found for O₂ extraction ratios and relative contributions of arteriolar, venular, and capillary gas fluxes for each type of deficit. The Fåhraeus effect and O₂–Hb kinetics reduced O₂ extraction in all cases and altered microcirculatory gas distributions depending on the specific type of O₂ supply deficits. The modified model continues to predict that capillaries are the major site where gas exchange takes place, and demonstrates that the Fåhraeus effect and nonequilibrium O₂–Hb kinetics are important mechanisms that should not be neglected in O₂ and CO₂ transport modeling. While this model provides useful insight regarding the influence of the Fåhraeus effect and O₂–Hb kinetics under steady state, the addition of a distributed and dynamic simulation should further elucidate the effects of the brain's heterogeneous properties and transient behavior. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 8745Ft, 8722-q     

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.     

Respiratory response to arterial H+ at different levels of arterialP_{{\text{CO}}_{\text{2}} } during hyperoxia or hypoxia

Summary Experiments were carried out in 12 dogs anesthetized with halothane of constant alveolar concentration (mean: 0.89%). The ventilatory response to arterial with hyperoxia was determined in metabolic acidosis (by infusion of 0.5 N HCl solution). The ventilatory response to arterial with constant hypoxia (about 50 mm Hg arterial ) was determined in both metabolic acidosis and alkalosis (by infusion of 1 M NaHCO₃ solution).The arterial H⁺-ventilation response curve was obtained at different constant levels of by simultaneous analysis of the -H⁺ diagram and the -ventilation response curve. Ventilation in hyperoxia was largely dependent on if acid-base balance was near normal, but became independent of and dependent on arterial H⁺ as this increased. It was postulated that this was partly due to the negative interaction between and H⁺. The H⁺-ventilation response curves showed the same pattern in hypoxia, but only on the alkalotic side. However, with hypoxia in the range of normal to acidotic condition, control of ventilation was mainly dependent on H⁺ and independent of ; this implies an interaction between hypoxia and H⁺ at the peripheral chemoreceptors.