Fetal breathing, sleep state, and cardiovascular responses to graded anemia in sheep

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2-3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.     

Exercise responses in pregnant sheep: oxygen consumption, uterine blood flow, and blood volume

In an attempt to explore the acute maternal responses to exercise we measured oxygen consumption, uterine blood flow, and blood volume in 13 chronically catheterized pregnant sheep at rest and while exercising on a treadmill. With maximal exercise O2 consumption increased 5.6 times, from a resting value of 5.8 +/- 0.3 (SE) to 32.1 +/- 2.8 ml X min -1 X kg -1, cardiac output increased 2.7 times, from 149 +/- 8 to 404 +/- 32 ml X min -1 X kg -1, and arteriovenous oxygen content difference increased 2.1 times, from 3.9 +/- 0.2 to 8.0 +/- 0.4 ml X dl -1. Total uterine blood flow decreased from a mean resting value of 292 +/- 6 to 222 +/- 19 ml X min -1 X kg fetus -1 near exhaustion during prolonged (40 min) exercise at 70% maximal oxygen consumption. Maternal blood volume decreased 14% (P less than 0.01) from 67.5 +/- 3.7 to 57.8 +/- 3.6 ml X kg -1 during this exercise period, with a 20% decrease in plasma volume without a change in red cell volume. We conclude that uterine blood flow decreases during maternal exercise. However, hemoconcentration helps to maintain a relatively constant oxygen delivery to the uterus.     

Behavioral activity during prolonged hypoxemia in fetal sheep

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.     

Fetal breathing and sleep state responses to graded carboxyhemoglobinemia in sheep

To investigate CO effects on brain oxygenation, graded carboxyhemoglobinemia (HbCO) was produced in nine unanesthetized fetal sheep by infusing CO-laden erythrocytes in exchange for fetal blood. For the 1st h after this procedure, the mean fetal carboxyhemoglobin levels were 16.5 +/- 0.4% [control (C) = 1.4 +/- 0.4%] for mild HbCO, 22.7 +/- 0.6% (C = 1.8 +/- 0.4%) for moderate HbCO, and 27.8 +/- 0.5% (C = 2.1 +/- 0.7%) for severe HbCO. This induction of HbCO significantly reduced mean preductal arterial PO2 values to 4.3 Torr below control for mild HbCO, 4.6 Torr below control for moderate HbCO, and 5.5 Torr below control for severe HbCO. The respective arterial O2 contents were decreased by 17, 21, and 29%. Mean arterial pH was lowered only during severe HbCO, and arterial PCO2 values were unchanged. HbCO produced a fetal tachycardia. Mean arterial blood pressure was only increased during severe HbCO. The incidences of rapid eye movements and breathing activity were decreased by HbCO in a dose-dependent manner. When related to calculated brain tissue PO2, these decreases were similar to those measured during hypoxic hypoxia and anemia, suggesting that carboxyhemoglobin effects result solely from diminished oxygenation. It is concluded that 1) the peripheral arterial chemoreceptors in the fetus apparently have little effect on hypoxic inhibition of breathing and 2) the carboxyhemoglobin concentrations required to inhibit fetal breathing are greater than those likely to be encountered clinically.     

Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.     

Arterial blood gases and acid-base status of dogs during graded dynamic exercise

The objective of this study was to determine whether arterial PCO2 (PaCO2) decreases or remains unchanged from resting levels during mild to moderate steady-state exercise in the dog. To accomplish this, O2 consumption (VO2) arterial blood gases and acid-base status, arterial lactate concentration ([LA-]a), and rectal temperature (Tr) were measured in 27 chronically instrumented dogs at rest, during different levels of submaximal exercise, and during maximal exercise on a motor-driven treadmill. During mild exercise [35% of maximal O2 consumption (VO2 max)], PaCO2 decreased 5.3 +/- 0.4 Torr and resulted in a respiratory alkalosis (delta pHa = +0.029 +/- 0.005). Arterial PO2 (PaO2) increased 5.9 +/- 1.5 Torr and Tr increased 0.5 +/- 0.1 degree C. As the exercise levels progressed from mild to moderate exercise (64% of VO2 max) the magnitude of the hypocapnia and the resultant respiratory alkalosis remained unchanged as PaCO2 remained 5.9 +/- 0.7 Torr below and delta pHa remained 0.029 +/- 0.008 above resting values. When the exercise work rate was increased to elicit VO2 max (96 +/- 2 ml X kg-1 X min-1) the amount of hypocapnia again remained unchanged from submaximal exercise levels and PaCO2 remained 6.0 +/- 0.6 Torr below resting values; however, this response occurred despite continued increases in Tr (delta Tr = 1.7 +/- 0.1 degree C), significant increases in [LA-]a (delta [LA-]a = 2.5 +/- 0.4), and a resultant metabolic acidosis (delta pHa = -0.031 +/- 0.011). The dog, like other nonhuman vertebrates, responded to mild and moderate steady-state exercise with a significant hyperventilation and respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute anemic hypoxemia produces a transient depression in fetal respiratory activity

Isovolemic anemia was produced in 11 unanesthetized fetal sheep by withdrawal of blood and replacement with saline-dextran. Fetal hematocrit fell from 36 +/- 1 to 19 +/- 1% (SE). Fetal breathing movements, which were present during 34.4 +/- 5.5% of 3 h before the anemia, occurred 10.1 +/- 5.3, 14.8 +/- 4.4, and 27.1 +/- 6.7% in the 3 h following. The anemia caused a fall in arterial O2 concentration from 8.4 +/- 0.3 to 3.6 +/- 0.1 vol% and sagittal vein PO2 fell from 15.4 +/- 0.5 to 12.4 +/- 0.3 Torr. Cerebral metabolic rate during the period of anemia was 2.9 +/- 0.1 ml.100 g-1.min-1, which was unchanged from the control value of 3.0 +/- 0.2 ml.100 g-1.min-1. Sagittal vein PCO2 (54.2 +/- 1.4 Torr) remained constant after the fetus was made anemic. We conclude that respiratory activity in the sheep fetus is depressed by anemic hypoxemia but that the effect is transient.     

Breath holding during intense exercise: arterial blood gases, pH, and lactate

Seven healthy endurance-trained [maximal O2 uptake (VO2max) = 57.1 +/- 4.1 ml.kg-1.min-1)] female volunteers (mean age 24.4 +/- 3.6 yr) served as subjects in an experiment measuring arterial blood gases, acid-base status, and lactate changes while breath holding (BH) during intense intermittent exercise. By the use of a counterbalance design, each subject repeated five intervals of a 15-s on:30-s off treadmill run at 125% VO2max while BH and while breathing freely (NBH). Arterial blood for pH, PO2, PCO2, O2 saturation (SO2) HCO3, and lactate was sampled from a radial arterial catheter at the end of each work and rest interval and throughout recovery, and the results were analyzed using repeated-measures analysis of variance. Significant reductions in pHa (delta mean = 0.07, P less than 0.01), arterial PO2 (delta mean = 24.2 Torr, P less than 0.01), and O2 saturation (delta mean = 4.6%, P less than 0.01) and elevations in arterial PCO2 (delta mean = 8.2 Torr, P less than 0.01) and arterial HCO3 (delta mean = 1.3 meq/l, P = 0.05) were found at the end of each exercise interval in the BH condition. All of the observed changes in arterial blood gases and acid-base status induced by BH were reversed during the rest intervals. During recovery, significantly (P less than 0.025) greater levels of arterial lactate were found in the BH condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bicarbonate attenuates arterial desaturation during maximal exercise in humans.

The contribution of pH to exercise-induced arterial O2 desaturation was evaluated by intravenous infusion of sodium bicarbonate (Bic, 1 M; 200-350 ml) or an equal volume of saline (Sal; 1 M) at a constant infusion rate during a "2,000-m" maximal ergometer row in five male oarsmen. Blood-gas variables were corrected to the increase in blood temperature from 36.5 +/- 0.3 to 38.9 +/- 0.1 degrees C (P < 0.05; means +/- SE), which was established in a pilot study. During Sal exercise, pH decreased from 7.42 +/- 0.01 at rest to 7.07 +/- 0.02 but only to 7.34 +/- 0.02 (P < 0.05) during the Bic trial. Arterial PO2 was reduced from 103.1 +/- 0.7 to 88.2 +/- 1.3 Torr during exercise with Sal, and this reduction was not significantly affected by Bic. Arterial O2 saturation was 97.5 +/- 0.2% at rest and decreased to 89.0 +/- 0.7% during Sal exercise but only to 94.1 +/- 1% with Bic (P < 0.05). Arterial PCO2 was not significantly changed from resting values in the last minute of Sal exercise, but in the Bic trial it increased from 40.5 +/- 0.5 to 45.9 +/- 2.0 Torr (P < 0.05). Pulmonary ventilation was lowered during exercise with Bic (155 +/- 14 vs. 142 +/- 13 l/min; P < 0.05), but the exercise-induced increase in the difference between the end-tidal O2 pressure and arterial PO2 was similar in the two trials. Also, pulmonary O2 uptake and changes in muscle oxygenation as determined by near-infrared spectrophotometry during exercise were similar. The enlarged blood-buffering capacity after infusion of Bic attenuated acidosis and in turn arterial desaturation during maximal exercise.     

Effects of acetazolamide on cerebral acid-base balance

Acetazolamide (AZ) inhibition of brain and blood carbonic anhydrase increases cerebral blood flow by acidifying cerebral extracellular fluid (ECF). This ECF acidosis was studied to determine whether it results from high PCO2, carbonic acidosis (accumulation of H2CO3), or lactic acidosis. Twenty rabbits were anesthetized with pentobarbital sodium, paralyzed, and mechanically ventilated with 100% O2. The cerebral cortex was exposed and fitted with thermostatted flat-surfaced pH and PCO2 electrodes. Control values (n = 14) for cortex ECF were pH 7.10 +/- 0.11 (SD), PCO2 42.2 +/- 4.1 Torr, PO2 107 +/- 17 Torr, HCO3- 13.8 +/- 3.0 mM. Control values (n = 14) for arterial blood were arterial pH (pHa) 7.46 +/- 0.03 (SD), arterial PCO2 (PaCO2) 32.0 +/- 4.1 Torr, arterial PO2 (PaO2) 425 +/- 6 Torr, HCO3- 21.0 +/- 2.0 mM. After intravenous infusion of AZ (25 mg/kg), end-tidal PCO2 and brain ECF pH immediately fell and cortex PCO2 rose. Ventilation was increased in nine rabbits to bring ECF PCO2 back to control. The changes in ECF PCO2 then were as follows: pHa + 0.04 +/- 0.09, PaCO2 -8.0 +/- 5.9 Torr, HCO3(-)-2.7 +/- 2.3 mM, PaO2 +49 +/- 62 Torr, and changes in cortex ECF were as follows: pH -0.08 +/- 0.04, PCO2 -0.2 +/- 1.6 Torr, HCO3(-)-1.7 +/- 1.3 mM, PO2 +9 +/- 4 Torr. Thus excess acidity remained in ECF after ECF PCO2 was returned to control values. The response of intracellular pH, high-energy phosphate compounds, and lactic acid to AZ administration was followed in vivo in five other rabbits with 31P and 1H nuclear magnetic resonance spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood-gas equilibration of CO2 and O2 in lungs of awake dogs during prolonged rebreathing

To reinvestigate the blood-gas CO2 equilibrium in lungs, rebreathing experiments were performed in five unanesthetized dogs prepared with a chronic tracheostomy and an exteriorized carotid loop. The rebreathing bag was initially filled with a gas mixture containing 6-8% CO2, 12, 21, or 39% O2, and 1% He in N2. During 4-6 min of rebreathing PO2 in the bag was kept constant by a controlled supply of O2 while PCO2 rose steadily from approximately 40 to 75 Torr. Spot samples of arterial blood were taken from the carotid loop; their PCO2 and PO2 were measured by electrodes and compared with the simultaneous values of end-tidal gas read from a mass spectrometer record. The mean end-tidal-to-arterial PO2 differences averaging 16, 4, and 0 Torr with bag PO2 about 260, 130, and 75 Torr, respectively, were in accordance with a venous admixture of about 1%. No substantial PCO2 differences between arterial blood and end-tidal gas (PaCO2 - PE'CO2) were found. The mean PaCO2 - PE'CO2 of 266 measurements in 70 rebreathing periods was -0.4 +/- 1.4 (SD) Torr. There was no correlation between PaCO2 - PE'CO2 and the level of arterial PCO2 or PO2. The mean PaCO2 - PE'CO2 became +0.1 Torr when the blood transit time from lungs to carotid artery (estimated at 6 s) and the rate of rise of bag PCO2 (4.5 Torr/min) were taken into account. These experimental results do not confirm the presence of significant PCO2 differences between arterial blood and alveolar gas in rebreathing equilibrium.     

Mechanical constraints on exercise hyperpnea in endurance athletes.

We determined how close highly trained athletes [n = 8; maximal oxygen consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits for generating expiratory airflow and inspiratory pleural pressure during maximal short-term exercise. Mechanical limits to expiratory flow were assessed at rest by measuring, over a range of lung volumes, the pleural pressures beyond which no further increases in flow rate are observed (Pmaxe). The capacity to generate inspiratory pressure (Pcapi) was also measured at rest over a range of lung volumes and flow rates. During progressive exercise, tidal pleural pressure-volume loops were measured and plotted relative to Pmaxe and Pcapi at the measured end-expiratory lung volume. During maximal exercise, expiratory flow limitation was reached over 27-76% of tidal volume, peak tidal inspiratory pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were generally reached coincident with the achievement of VO2max; the greater the ventilatory response, the greater was the degree of mechanical limitation. Mean arterial blood gases measured during maximal exercise showed a moderate hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of hypoxemia (arterial PO2 = 78 Torr, range 65-83 Torr). Increasing the stimulus to breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 = 65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory pressure, or expiratory pressure. We conclude that during maximal exercise, highly trained individuals often reach the mechanical limits of the lung and respiratory muscle for producing alveolar ventilation. This level of ventilation is achieved at a considerable metabolic cost but with a mechanically optimal pattern of breathing and respiratory muscle recruitment and without sacrifice of a significant alveolar hyperventilation.     

Evaluation of factors affecting relationship between transcutaneous PO2 and probe temperature

Several studies on transcutaneous O2 probes have shown that the transcutaneous PO2 increases to approximately 80% of the arterial PO2 when the probe is heated to 44 degrees C. It is not known whether this result reflects near-complete thermic arterialization or rather other factors such as the temperature-linked right shift of the hemoglobin O2-binding curve. In many clinical applications of transcutaneous probes the use of 44 degrees C is a major disadvantage because of the risk of skin burns. The development of new probes operating at lower temperatures is hampered by the lack of data on the temperature dependence of the factors influencing the relationship between the transcutaneous PO2 and the probe temperature. The present study attempts to estimate the temperature dependence of 1) the degree of arterialization of the blood in the skin capillaries, 2) the PO2 difference across the epidermis caused by the diffusion gradient and the epidermal O2 consumption, and 3) the arteriovenous saturation difference over the skin capillaries. The estimation is based on simultaneously measured transcutaneous PO2, PCO2, and argon partial pressure (PAr) values at seven different probe temperatures. The transcutaneous PCO2 is assumed equal to the mean capillary PCO2, which is used to calculate the mean capillary PO2 by the aid of a skin model. The O2 diffusion gradient is estimated from the transcutaneous PAr, and the PO2 difference caused by the epidermal O2 consumption is set equal to the difference between the mean capillary and transcutaneous PO2 less the partial pressure difference caused by the diffusion gradient. The degree of arterialization was found to be 53% at 38 degrees C and 65% at 44 degrees C. The partial pressure difference caused by the epidermal O2 consumption decreased from 33 Torr at 38 degrees C to 6 Torr at 44 degrees C. The PO2 difference across the epidermis caused by the diffusion gradient was 7 Torr at 38 degrees C and 5 Torr at 44 degrees C. The arteriovenous saturation difference fell from 31% at 38 degrees C to 12% at 44 degrees C.     

Operation Everest II: oxygen transport during exercise at extreme simulated altitude

A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained previously. In this study we examined eight healthy males, aged 21-31 yr, at rest and during steady-state exercise at sea level and the following inspired O2 pressures (PIO2): 80, 63, 49, and 43 Torr, during a 40-day simulated ascent of Mt. Everest. The subjects exercised on a cycle ergometer, and heart rate was recorded by an electrocardiograph; ventilation, O2 uptake, and CO2 output were measured by open circuit. Arterial and mixed venous blood samples were collected from indwelling radial or brachial and pulmonary arterial catheters for analysis of blood gases, O2 saturation and content, and lactate. As PIO2 decreased, maximal O2 uptake decreased from 3.98 +/- 0.20 l/min at sea level to 1.17 +/- 0.08 l/min at PIO2 43 Torr. This was associated with profound hypoxemia and hypocapnia; at 60 W of exercise at PIO2 43 Torr, arterial PO2 = 28 +/- 1 Torr and PCO2 = 11 +/- 1 Torr, with a marked reduction in mixed venous PO2 [14.8 +/- 1 (SE) Torr]. Considering the major factors responsible for transfer of O2 from the atmosphere to the tissues, the most important adaptations occurred in ventilation where a fourfold increase in alveolar ventilation was observed. Diffusion from alveolus to end-capillary blood was unchanged with altitude. The mass circulatory transport of O2 to the tissue capillaries was also unaffected by altitude except at PIO2 43 Torr where cardiac output was increased for a given O2 uptake. Diffusion from the capillary to the tissue mitochondria, reflected by mixed venous PO2, was also increased with altitude. With increasing altitude, blood lactate was progressively reduced at maximal exercise, whereas at any absolute and relative submaximal work load, blood lactate was higher. These findings suggest that although glycogenolysis may be accentuated at low work loads, it may not be maximally activated at exhaustion.     

The response of the umbilical artery pulsatility index in fetal sheep to acute and prolonged hypoxaemia and acidaemia induced by embolization of the uterine microcirculation

In eight chronically-instrumented sheep, embolization of the uterine microcirculation was performed to evaluate the response of the umbilical artery pulsatility index to prolonged fetal hypoxaemia and acidaemia. From four days after surgery onwards, fetal arterial oxygen content [( O2]a) was progressively reduced by administration of microspheres into the uterine circulation. Measurements included fetal [O2]a, PO2, PCO2, pH, base excess, heart rate, blood pressure and umbilical artery pulsatility index. Fetal survival varied between less than 2 and less than 8 days, while mean fetal survival was less than 4 days. From baseline condition to the last evaluation preceding the diagnosis of fetal death, [O2]a decreased from 3.10 +/- 0.36 to 0.87 +/- 0.27 mM, pH decreased from 7.36 +/- 0.03 to 7.22 +/- 0.08, base excess decreased from -0.3 +/- 1.5 to -7.3 +/- 3.2 and blood pressure increased from 35.0 +/- 7.1 to 40.7 +/- 8.7 (means +/- SD). The umbilical artery pulsatility index (1.05 +/- 0.19 at baseline condition) did not significantly change (1.08 +/- 0.12 prior to fetal death). It is concluded that a condition of prolonged hypoxaemia and acidaemia in fetal sheep, induced by repeated embolizations of the uterine circulation, is not associated with consistent changes in the umbilical artery pulsatility index.     

Time course of muscular blood metabolites during forearm rhythmic exercise in hypoxia

O2 concentration, PO2, PCO2, pH, osmolarity, lactate (LA), and hemoglobin (Hb) concentrations in deep forearm venous blood were repeatedly measured during submaximal exercise of forearm muscles. Concentrations of arterial blood gases were determined at rest and during exercise. Experiments were conducted under normoxia and hypobaric hypoxia (PB = 465 Torr). In arterial blood, data obtained during exercise were the same as those obtained during rest under either normoxia or hypoxia. In venous muscular blood, PO2 and O2 concentration were lower at rest and during exercise in hypoxia. The muscular arteriovenous O2 difference during exercise in hypoxia was increased by no more than 10% compared with normoxia, which implied that muscular blood flow during exercise also increased by the same percentage, if we assume that exercise O2 consumption was not affected by hypoxia. Despite increased [LA], the magnitude of changes in PCO2 and pH in hypoxia were smaller than in normoxia during exercise and recovery; this finding is probably due to the increased blood buffer value induced by the greater amount of reduced Hb in hypoxia. Hence all the changes occurring in hypoxia showed that local metabolism was less affected than we expected from the decrease in arterial PO2. The rise in [Hb] that occurred during exercise was lower in hypoxia. Possible underlying mechanisms of the [Hb] rise during exercise are discussed.     

Pulmonary gas exchange and acid-base state at 5,260 m in high-altitude Bolivians and acclimatized lowlanders.

Pulmonary gas exchange and acid-base state were compared in nine Danish lowlanders (L) acclimatized to 5,260 m for 9 wk and seven native Bolivian residents (N) of La Paz (altitude 3,600-4,100 m) brought acutely to this altitude. We evaluated normalcy of arterial pH and assessed pulmonary gas exchange and acid-base balance at rest and during peak exercise when breathing room air and 55% O2. Despite 9 wk at 5,260 m and considerable renal bicarbonate excretion (arterial plasma HCO3- concentration = 15.1 meq/l), resting arterial pH in L was 7.48 +/- 0.007 (significantly greater than 7.40). On the other hand, arterial pH in N was only 7.43 +/- 0.004 (despite arterial O2 saturation of 77%) after ascent from 3,600-4,100 to 5,260 m in 2 h. Maximal power output was similar in the two groups breathing air, whereas on 55% O2 only L showed a significant increase. During exercise in air, arterial PCO2 was 8 Torr lower in L than in N (P < 0.001), yet PO2 was the same such that, at maximal O2 uptake, alveolar-arterial PO2 difference was lower in N (5.3 +/- 1.3 Torr) than in L (10.5 +/- 0.8 Torr), P = 0.004. Calculated O2 diffusing capacity was 40% higher in N than in L and, if referenced to maximal hyperoxic work, capacity was 73% greater in N. Buffering of lactic acid was greater in N, with 20% less increase in base deficit per millimole per liter rise in lactate. These data show in L persistent alkalosis even after 9 wk at 5,260 m. In N, the data show 1) insignificant reduction in exercise capacity when breathing air at 5,260 m compared with breathing 55% O2; 2) very little ventilatory response to acute hypoxemia (judged by arterial pH and arterial PCO2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial PO2 despite lower ventilation; and 4) better buffering of lactic acid. These results support and extend similar observations concerning adaptation in lung function in these and other high-altitude native groups previously performed at much lower altitudes.     

Cerebral metabolic and pressure-flow responses during sustained hypoxia in awake sheep.

Conscious sheep (n = 6), exposed to 3.5 h of normobaric hypoxia (arterial PO2 = 40 Torr) while allowed varying arterial PCO2, showed striking early increments of cerebral blood flow (CBF; +200-250%, by radiolabeled microspheres) and decrements of cerebral vascular resistance (CVR) in association with an early temporary elevation of cerebral O2 consumption (CMRO2; +25-60%). After 2 h, CMRO2 returned to normoxic levels, while CBF declined to a lower but still elevated level (+150%). CBF/CMRO2 increased twofold, while cerebral fractional extraction of O2 was unchanged. Mean arterial pressure was unchanged, but cerebral venous pressure rose (+11 mmHg) in a stable fashion such that cerebral perfusion pressure declined by 13%. Cerebral venous hematocrit and hemoglobin concentration were both elevated (+2.2-2.7% Hct units; +1.0-1.3 g/dl, respectively) above the corresponding arterial values between 150 and 210 min of hypoxia, suggesting venous hemoconcentration in possible association with a transcapillary fluid shift. CBF, and especially CVR, were well correlated with arterial O2 content.     

Chronic administration of sodium cyanate decreases O2 extraction ratio in dogs

It has been proposed that an increase in the affinity of hemoglobin for O2 may be beneficial in severe hypoxemia. To test this hypothesis, we compared the response to progressive hypoxemia in dogs with normal hemoglobin affinity (P50 = 32.4 +/- 0.7 Torr) to dogs with a left shift of the oxyhemoglobin dissociation curve (P50 = 21.9 +/- 0.5 Torr) induced by chronic oral administration of sodium cyanate. Animals were anesthetized, paralyzed, and mechanically ventilated. The inspired O2 fraction was progressively lowered by increasing the inspired fraction of N2. The lowest level of O2 transport required to maintain base-line O2 consumption (VO2) was 9.3 +/- 0.8 ml.min-1.kg-1 for control and 16.5 +/- 1.1 ml.min-1.kg-1 for the sodium cyanate-treated dogs (P less than 0.01). Other measured parameters at this level of O2 transport were, for experimental vs. control: arterial PO2 19.3 +/- 2.4 (SE) Torr vs. 21.8 +/- 1.6 Torr (NS); arterial O2 content 10.0 +/- 1.2 ml/dl vs. 4.9 +/- 0.4 ml/dl (P less than 0.01); mixed venous PO2 14.0 +/- 1.5 Torr vs. 13.8 +/- 1.0 Torr (NS); mixed venous O2 content 6.8 +/- 1.0 ml/dl vs. 2.3 +/- 0.2 ml/dl (P less than 0.01); and O2 extraction ratio 32.7 +/- 2.8% vs. 51.2 +/- 3.8% (P less than 0.01). We conclude that chronic administration of sodium cyanate appears to be detrimental to O2 transport, since the experimental dogs were unable to increase their O2 extraction ratios to the same level as control, thus requiring a higher level of O2 transport to maintain their base-line VO2 values.     

Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans

The effects of mild hypoxia on brain oxyhemoglobin, cytochrome a,a3 redox status, and cerebral blood volume were studied using near-infrared spectroscopy in eight healthy volunteers. Incremental hypoxia reaching 70% arterial O2 saturation was produced in normocapnia [end-tidal PCO2 (PETCO2) 36.9 +/- 2.6 to 34.9 +/- 3.4 Torr] or hypocapnia (PETCO2 32.8 +/- 0.6 to 23.7 +/- 0.6 Torr) by an 8-min rebreathing technique and regulation of inspired CO2. Normocapnic hypoxia was characterized by progressive reductions in arterial PO2 (PaO2, 89.1 +/- 3.5 to 34.1 +/- 0.1 Torr) with stable PETCO2, arterial PCO2 (PaCO2), and arterial pH and resulted in increases in heart rate (35%) systolic blood pressure (14%), and minute ventilation (5-fold). Hypocapnic hypoxia resulted in progressively decreasing PaO2 (100.2 +/- 3.6 to 28.9 +/- 0.1 Torr), with progressive reduction in PaCO2 (39.0 +/- 1.6 to 27.3 +/- 1.9 Torr), and an increase in arterial pH (7.41 +/- 0.02 to 7.53 +/- 0.03), heart rate (61%), and ventilation (3-fold). In the brain, hypoxia resulted in a steady decline of cerebral oxyhemoglobin content and a decrease in oxidized cytochrome a,a3. Significantly greater loss of oxidized cytochrome a,a3 occurred for a given decrease in oxyhemoglobin during hypocapnic hypoxia relative to normocapnic hypoxia. Total blood volume response during hypoxia also was significantly attenuated by hypocapnia, because the increase in volume was only half that of normocapnic subjects. We conclude that cytochrome a,a3 oxidation level in vivo decreases at mild levels of hypoxia. PaCO is an important determinant of brain oxygenation, because it modulates ventilatory, cardiovascular, and cerebral O2 delivery responses to hypoxia.