Mechanism of transient nocturnal hypoxemia in hypoxic chronic bronchitis and emphysema

In five patients with hypoxic chronic bronchitis and emphysema we measured ear O2 saturation (SaO2), chest movement, oronasal airflow, arterial and mixed venous gas tensions, and cardiac output during nine hypoxemic episodes (HE; SaO2 falls greater than 10%) in rapid-eye-movement (REM) sleep and during preceding periods of stable oxygenation in non-REM sleep. All nine HE occurred with recurrent short episodes of reduced chest movement, none with sleep apnea. The arterial PO2 (PaO2) fell by 6.0 +/- 1.9 (SD) Torr during the HE (P less than 0.01), but mean arterial PCO2 (PaCO2) rose by only 1.4 +/- 2.4 Torr (P greater than 0.4). The arteriovenous O2 content difference fell by 0.64 +/- 0.43 ml/100 ml of blood during the HE (P less than 0.05), but there was no significant change in cardiac output. Changes observed in PaO2 and PaCO2 during HE were similar to those in four normal subjects during 90 s of voluntary hypoventilation, when PaO2 fell by 12.3 +/- 5.6 Torr (P less than 0.05), but mean PaCO2 rose by only 2.8 +/- 2.1 Torr (P greater than 0.4). We suggest that the transient hypoxemia which occurs during REM sleep in patients with chronic bronchitis and emphysema could be explained by hypoventilation during REM sleep but that the importance of changes in distribution of ventilation-perfusion ratios cannot be assessed by presently available techniques.     

Maximum oxygen uptake and arterial blood oxygenation during hypoxic exercise in rats.

The objectives of these experiments were 1) to describe the effect of maximum treadmill exercise on gas exchange, arterial blood gases, and arterial blood oxygenation in rats acclimated for 3 wk to simulated altitude (SA, barometric pressure 370-380 Torr) and 2) to determine the contribution of acid-base changes to the changes in arterial blood oxygenation of hypoxic exercise. Maximum O2 uptake (VO2max) was measured in four groups of rats: 1) normoxic controls run in normoxia (Nx), 2) normoxic controls run in acute hypoxia [AHx inspiratory PO2 (PIO2) approximately 70 Torr], 3) SA rats run in hypoxia (3WHx, PIO2 approximately 70 Torr), and 4) SA rats run in normoxia (ANx). VO2max (ml STPD.min-1.kg-1) was 70.8 +/- 0.9 in Nx, 46.4 +/- 1.9 in AHx, 52.6 +/- 1.1 in 3WHx, and 70.0 +/- 2.4 in ANx. Exercise resulted in acidosis, hypocapnia, and elevated blood lactate in all groups. Although blood lactate increased less in 3WHx and ANx, pH was the same or lower than in Nx and AHx, reflecting the low buffer capacity of SA. In AHx and 3WHx, arterial PO2 increased with exercise; however, O2 saturation of hemoglobin in arterial blood (SaO2) decreased. In vitro measurements of the Bohr shift suggest that SaO2 decreased as a result of a decrease in hemoglobin O2 affinity. The data indicate that several features of hypoxic exercise in this model are similar to those seen in humans, with the exception of the mechanism of decrease in SaO2, which, in humans, appears to be due to incomplete alveolar-capillary equilibration.     

Ventrolateral medullary surface blood flow determined by hydrogen clearance

The H2 clearance technique was used to determine the blood flow of the postulated respiratory chemosensitive areas near the ventrolateral surface of the medulla. In 12 pentobarbital sodium-anesthetized cats, flow (mean +/- SD) was measured from 25-micron Teflon-coated platinum wire electrodes implanted to a depth of 0.3-0.7 mm. Flow (in ml X min-1 X 100 g-1, n = 35) was 52.8 +/- 28.5 in hypocapnia [arterial CO2 partial pressure (PaCO2) = 21.8 +/- 1.6 Torr], 57.8 +/- 27.5 in normocapnia (PaCO2 = 31.9 +/- 2.2 Torr), and 75.0 +/- 31.7 in hypercapnia (PaCO2 = 44.5 +/- 3.0 Torr). Flow determined from 15 electrodes in adjacent pyramidal tracts (white matter) was less at all levels of CO2; 22.9 +/- 12.3 in hypocapnia, 29.1 +/- 15.9 in normocapnia, and 33.9 +/- 13.9 in hypercapnia. In hypoxia [arterial O2 partial pressure (PaO2) = 39.9 +/- 6.3 Torr] ventrolateral surface flow rose to 87.9 +/- 47.6, and adjacent white matter flow was 35.8 +/- 15.6. These results indicate that flow in the postulated central chemoreceptor areas exceeds that of white matter and is sensitive to variations in PaCO2 and PaO2.     

Role of plasma adenosine in breathing responses to hypoxia in fetal sheep.

The importance of plasma adenosine in hypoxic inhibition of breathing movements was determined in chronically catheterized fetal sheep (greater than 0.8 term). Preductal arterial blood for adenosine measurements was withdrawn using a double lumen catheter to mix blood entering the catheter with a solution to stop adenosine metabolism. In 6 fetuses, isocapnic hypoxia (delta PaO2 congruent to -10 Torr) increased the average plasma adenosine concentration from 1.1 +/- 0.2 (SEM) to 2.0 to +/- 0.4 microM. During hypoxia, plasma levels of adenosine were inversely related to preductal arterial O2 content (CaO2) with values ranging between 1.6 and 4.0 microM when CaO2 was less than 3 ml/dl. Hypoxia also significantly reduced the incidence of fetal breathing and rapid eye movements. In other experiments, adenosine (0.36 +/- 0.03 mg/min/kg) was infused for one hour into the inferior vena cava of 5 fetuses. During this infusion, mean plasma concentration of adenosine was 2.8 +/- 0.3 microM, a value about 2.5 times the control average. Adenosine also significantly reduced the incidence of low voltage electrocortical activity, rapid eye movements and breathing activity. We conclude that hypoxic inhibition of fetal breathing most likely arises from an increase in central adenosine production, although during severe O2 deprivation (CaO2 less than 3 ml/dl) blood-borne adenosine could also contribute.     

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)     

Costal diaphragmatic O2 and lactate extraction in laryngeal hemiplegic ponies during exercise

Diaphragmatic O2 and lactate extraction were examined in seven healthy ponies during maximal exercise (ME) carried out without, as well as with, inspiratory resistive breathing. Arterial and diaphragmatic venous blood were sampled simultaneously at rest and at 30-s intervals during the 4 min of ME. Experiments were carried out before and after left laryngeal hemiplegia (LH) was produced. During ME, normal ponies exhibited hypocapnia, hemoconcentration, and a decrease in arterial PO2 (PaO2) with insignificant change in O2 saturation. In LH ponies, PaO2 and O2 saturation decreased well below that in normal ponies, but because of higher hemoglobin concentration, arterial O2 content exceeded that in normal ponies. Because of their high PaCO2 during ME, acidosis was more pronounced in LH animals despite similar lactate values. Diaphragmatic venous PO2 and O2 saturation decreased with ME to 15.5 +/- 0.9 Torr and 18 +/- 0.5%, respectively, at 120 s of exercise in normal ponies. In LH ponies, corresponding values were significantly less: 12.4 +/- 1.3 Torr and 15.5 +/- 0.7% at 120 s and 9.8 +/- 1.4 Torr and 14.3 +/- 0.6% at 240 s of ME. Mean phrenic O2 extraction plateaued at 81 and 83% in normal and LH animals, respectively. Significant differences in lactate concentration between arterial and phrenic-venous blood were not observed during ME. It is concluded that PO2 and O2 saturation in the phrenic-venous blood of normal ponies do not reach their lowest possible values even during ME. Also, the healthy equine diaphragm, even with the added stress of inspiratory resistive breathing, did not engage in net lactate production.     

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.     

Hypoxemia alone does not explain blood pressure elevations after obstructive apneas

In patients with obstructive sleep apnea (OSA), substantial elevations of systemic blood pressure (BP) and depressions of oxyhemoglobin saturation (SaO2) accompany apnea termination. The causes of the BP elevations, which contribute significantly to nocturnal hypertension in OSA, have not been defined precisely. To assess the relative contribution of arterial hypoxemia, we observed mean arterial pressure (MAP) changes following obstructive apneas in 11 OSA patients during non-rapid-eye-movement (NREM) sleep and then under three experimental conditions: 1) apnea with O2 supplementation; 2) hypoxemia (SaO2 80%) without apnea; and 3) arousal from sleep with neither hypoxemia nor apnea. We found that apneas recorded during O2 supplementation (SaO2 nadir 93.6% +/- 2.4; mean +/- SD) in six subjects were associated with equivalent postapneic MAP elevations compared with unsupplemented apneas (SaO2 nadir 79-82%): 18.8 +/- 7.1 vs. 21.3 +/- 9.2 mmHg (mean change MAP +/- SD); in the absence of respiratory and sleep disruption in eight subjects, hypoxemia was not associated with the BP elevations observed following apneas: -5.4 +/- 19 vs. 19.1 +/- 7.8 mmHg (P less than 0.01); and in five subjects, auditory arousal alone was associated with MAP elevation similar to that observed following apneas: 24.0 +/- 8.1 vs. 22.0 +/- 6.9 mmHg. We conclude that in NREM sleep postapneic BP elevations are not primarily attributable to arterial hypoxemia. Other factors associated with apnea termination, including arousal from sleep, reinflation of the lungs, and changes of intrathoracic pressure, may be responsible for these elevations.     

Chronic sodium cyanate treatment induces "hypoxia-like" effects in rats

Three weeks of sodium cyanate (NaCNO) intraperitoneal treatment in rats (n = 15) induced high hemoglobin O2 affinity, i.e., low PO2 at 50% hemoglobin saturation (P50), 20.5 +/- 1.4 Torr, in comparison with the mean control values, 34.5 +/- 1.6 Torr (n = 15). NaCNO rats showed a reduction in mean body weight, 376 +/- 27 g, in comparison with controls, 423 +/- 23 g (P less than 0.001). Despite arterial O2 partial pressure (PaO2) within normal limits NaCNO-treated rats had a higher systolic right ventricular pressure (SRVP), 33.7 +/- 3.1 Torr, in comparison with control value, 29.0 +/- 2.5 Torr (P less than 0.001). Right ventricle weights were significantly increased (P less than 0.001). After 60 min of an hypoxic challenge (fractional concentration of inspired O2 = 0.10) NaCNO-treated rats increased SRVP of only 7 +/- 4% compared with 46 +/- 9% in the control animals. Inducing high hemoglobin affinity in rats (n = 10; 6 wk NaCNO treatment) resulted in increases in hematocrit ratio and hemoglobin concentration (P less than 0.001). The characteristics of the red blood cell (RBC) itself changed; values of mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration being significantly increased (P less than 0.001) when compared with mean control values. The count of nucleated RBC's appeared to be significantly higher from the 2nd wk of NaCNO treatment. Chronic NaCNO treatment was demonstrated to exert "hypoxia-like" effects since it induced prevention of normal growth, polycythemia, pulmonary hypertension, right ventricular hypertrophy, and blunted pulmonary pressor response to acute hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary gas exchange in panting dogs

Pulmonary gas exchange during panting was studied in seven conscious dogs (32 kg mean body wt) provided with a chronic tracheostomy and an exteriorized carotid artery loop. The animals were acutely exposed to moderately elevated ambient temperature (27.5 degrees C, 65% relative humidity) for 2 h. O2 and CO2 in the tracheostomy tube were continuously monitored by mass spectrometry using a special sample-hold phase-locked sampling technique. PO2 and PCO2 were determined in blood samples obtained from the carotid artery. During the exposure to heat, central body temperature remained unchanged (38.6 +/- 0.6 degrees C) while all animals rapidly switched to steady shallow panting at frequencies close to the resonant frequency of the respiratory system. During panting, the following values were measured (means +/- SD): breathing frequency, 313 +/- 19 breaths/min; tidal volume, 167 +/- 21 ml; total ventilation, 52 +/- 9 l/min; effective alveolar ventilation, 5.5 +/- 1.3 l/min; PaO2, 106.2 +/- 5.9 Torr; PaCO2, 27.2 +/- 3.9 Torr; end-tidal-arterial PO2 difference [(PE' - Pa)O2], 26.0 +/- 5.3 Torr; and arterial-end-tidal PCO2 difference, [(Pa - PE')CO2], 14.9 +/- 2.5 Torr. On the basis of the classical ideal alveolar air approach, parallel dead-space ventilation accounted for 54% of alveolar ventilation and 66% of the (PE' - Pa)O2 difference. But the steepness of the CO2 and O2 expirogram plotted against expired volume suggested a contribution of series in homogeneity due to incomplete gas mixing.     

Ventral medullary extracellular fluid pH and PCO2 during hypoxemia

We designed experiments to study changes in ventral medullary extracellular fluid (ECF) PCO2 and pH during hypoxemia. Measurements were made in chloralose-urethan-anesthetized spontaneously breathing cats (n = 12) with peripherial chemodenervation. Steady-state measurements were made during normoxemia [arterial PO2 (PaO2) = 106 Torr], hypoxemia (PaO2 = 46 Torr), and recovery (PaO2 = 105 Torr), with relatively constant arterial PCO2 (approximately 44 Torr). Mean values of ventilation were 945, 683, and 1,037 ml/min during normoxemia, hypoxemia, and recovery from hypoxemia, respectively. Ventilatory depression occurred in each cat during hypoxemia. Mean values of medullary ECF PCO2 were 57.7 +/- 7.2 (SD), 59.4 +/- 9.7, and 57.4 +/- 7.2 Torr during normoxemia, hypoxemia, and recovery to normoxemia, respectively; respective values for ECF [H+] were 60.9 +/- 8.0, 64.4 +/- 11.6, and 62.9 +/- 9.2 neq/l. Mean values of calculated ECF [HCO3-] were 22.8 +/- 3.0, 21.7 +/- 3.3, and 21.4 +/- 3.1 meq/l during normoxemia, hypoxemia, and recovery, respectively. Changes in medullary ECF PCO2 and [H+] were not statistically significant. Therefore hypoxemia caused ventilatory depression independent of changes in ECF acid-base variables. Furthermore, on return to normoxemia, ventilation rose considerably, still independent of changes in ECF PCO2, [H+], and [HCO3-].     

Augmented hypoxic ventilatory response in men at altitude.

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of mean airway pressure on gas exchange during high-frequency oscillatory ventilation

We studied the effect of mean airway pressure (Paw) on gas exchange during high-frequency oscillatory ventilation in 14 adult rabbits before and after pulmonary saline lavage. Sinusoidal volume changes were delivered through a tracheostomy at 16 Hz, a tidal volume of 1 or 2 ml/kg, and inspired O2 fraction of 0.5. Arterial PO2 and PCO2 (PaO2, PaCO2), lung volume change, and venous admixture were measured at Paw from 5 to 25 cmH2O after either deflation from total lung capacity or inflation from relaxation volume (Vr). The rabbits were lavaged with saline until PaO2 was less than 70 Torr, and all measurements were repeated. Lung volume change was measured in a pressure plethysmograph. Raising Paw from 5 to 25 cmH2O increased lung volume by 48-50 ml above Vr in both healthy and lavaged rabbits. Before lavage, PaO2 was relatively insensitive to changes in Paw, but after lavage PaO2 increased with Paw from 42.8 +/- 7.8 to 137.3 +/- 18.3 (SE) Torr (P less than 0.001). PaCO2 was insensitive to Paw change before and after lavage. At each Paw after lavage, lung volume was larger, venous admixture smaller, and PaO2 higher after deflation from total lung capacity than after inflation from Vr. This study shows that the effect of increased Paw on PaO2 is mediated through an increase in lung volume. In saline-lavaged lungs, equal distending pressures do not necessarily imply equal lung volumes and thus do not imply equal PaO2.     

Role of hemoglobin P50 in O2 transport during normoxic and hypoxic exercise in the dog

High hemoglobin affinity for O2 [low PO2 at 50% saturation of hemoglobin (P50)] could degrade exercise performance in normoxia by lowering mean tissue PO2 but could enhance O2 transport in hypoxic exercise by increasing arterial O2 saturation. We measured O2 transport at rest and at graded levels of steady-state exercise in tracheostomized dogs with normal P50 (28.8 +/- 1.8 Torr) and again after P50 was lowered (19.5 +/- 0.7 Torr) by sodium cyanate infusions. Measurements were made during ventilation with room air (RA), 12% O2 in N2, or 10% O2 in N2. Cardiac output (QT) as a function of O2 consumption (VO2) was not altered by low P50 at any inspired O2 fraction (P greater than 0.05). With RA exercise, arterial content (CaO2) and O2 delivery (QT X CaO2) were unchanged at low P50, whereas mixed venous PO2 was reduced at each level of VO2. With exercise in hypoxia, CaO2 and O2 delivery were significantly improved at low P50 (P less than 0.05). Mixed venous PO2 was lower than control during 12% O2 (P less than 0.05) but not different from control during 10% O2 exercise at low P50. Despite a presumed decrease in tissue PO2 during RA and 12% O2 exercise, exercise performance and base excess decline were not significantly worse than control levels. We conclude that, in canine steady-state exercise, hemoglobin P50 is not an important determinant of tissue O2-extraction capacity during normoxia or moderate hypoxia. In extreme hypoxia, low P50 may help to maintain tissue PO2 by enhancing systemic O2 delivery at each level of QT.     

Circulating vasoactive substances and hemodynamic adjustments at birth in lambs

Circulating vasoactive substances and hemodynamics were examined in chronically instrumented unanesthetized lambs before, during, and after cesarean section (spontaneous respiration). One of three infusions were started 20 min before birth: saline control (n = 10), saralasin (n = 5), or captopril (n = 6). Control lambs exhibited peak (means +/- SE) increases above fetal base line at 5 min after birth in plasma renin activity (5.0 +/- 1.1 to 11.0 +/- 3.4 ng.ml-1.h-1), angiotensin II (ANG II, 37 +/- 6 to 141 +/- 45 pg/ml) and total catecholamines (318 +/- 35 to 3,821 +/- 580 pg/ml). Mean systemic arterial pressure (Psa) and arterial O2 partial pressure (PaO2) increased more rapidly and to a greater extent by 1 h after birth in control lambs (Psa, 65 +/- 1 Torr; PaO2, 45 +/- 3 Torr) compared with the captopril group (Psa, 53 +/- 2 Torr; PaO2, 31 +/- 4 Torr) and the saralasin group (Psa, 56 +/- 2 Torr; PaO2, 27 +/- 3 Torr). Intravenous infusions of ANG II in control lambs, 2 h after birth resulted in a preferential systemic vs. pulmonary pressor response. The results demonstrate that at birth ANG II formation fosters the postnatal rise in Psa and PaO2, and high levels of circulating catecholamines may support postnatal cardiac output and Psa.     

Relationship of venous PO2 to muscle PO2 during hypoxemia

Anesthetized mechanically ventilated rabbits were subjected to progressive hypoxemia (n = 7) to determine the relationship of venous PO2 (PvO2) to skeletal muscle PO2 (PtiO2). Measures of arterial PO2 (PaO2), right atrial PO2 [(PvO2)RA], and hindlimb PO2 [(PvO2)limb], were obtained from the carotid artery, right atrium, and inferior vena cava, just above the level of the iliac bifurcation. Biceps femoris muscle PtiO2 was measured with a surface O2 microelectrode having eight measuring points. PaO2 was decreased from 90.3 +/- 5.4 to 26.8 +/- 0.8 Torr in five consecutive steps, followed by reoxygenation to 105.6 +/- 10.5 (SE) Torr. Measurements were obtained after each decrement in PaO2. A total of 128 measures of PtiO2 were obtained per experimental stage. The mean and distribution of the muscle PtiO2 histogram were determined. Measurements were compared with analysis of variance and the Newman-Keuls post hoc method. (PvO2)limb had similar values as the average muscle PtiO2 (PtiO2) for PaO2 values greater than 52.1 +/- 4.3 Torr, where (PvO2)limb became greater than PtiO2 (P less than 0.05). The lowest measures of (PvO2)limb and PtiO2 were 15.9 +/- 0.7 and 4.0 +/- 0.1 Torr, respectively (P less than 0.01). The PtiO2 histograms showed no evidence of increased microvascular heterogeneity with hypoxemia. We conclude that in hypoxemia PvO2 is greater than muscle PtiO2. This difference may be related to the establishment of significant physicochemical O2 gradients from erythrocyte to tissue cell.     

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.     

Increased exercise SaO2 independent of ventilatory acclimatization at 4,300 m

Arterial O2 saturation (Sao2) decreases in hypoxia in the transition from rest to moderate exercise, but it is unknown whether other several weeks at high altitude SaO2 in submaximal exercise follows the same time course and pattern as that of ventilatory acclimatization in resting subjects. Ventilatory acclimatization is essentially complete after approximately 1 wk at 4,300 m, such that improvement in submaximal exercise SaO2 would then require other mechanisms. On days 2, 8, and 22 on Pikes Peak (4,300 m), 6 male subjects performed prolonged steady-state cycle exercise at 79% maximal O2 uptake (VO2 max). Resting SaO2 rose from day 1 (78.4 +/- 1.6%) to day 8 (87.5 +/- 1.4%) and then did not increase further by day 20 (86.4 +/- 0.6%). During exercise, SaO2 values (mean of 5-, 15-, and 30-min measurements) were 72.7% (day 2), 78.6% (day 8), and 82.3% (day 22), meaning that all of the increase in resting SaO2 occurred from day 1 to day 8, but exercise SaO2 increased from day 2 to day 8 (5.9%) and then increased further from day 8 to day 22 (3.7%). On day 22, the exercise SaO2 was higher than on day 8 despite an unchanged ventilation and O2 consumption. The increased exercise SaO2 was accompanied by decreased CO2 production. The mechanisms responsible for the increased exercise SaO2 require further investigation.     

Changes in hypoxanthine and lactate during and after hypoxia in the fetal sheep with chronically-implanted vascular catheters

The effect of intra-uterine hypoxia on the hypoxanthine and lactate concentration in fetal sheep with catheters chronically implanted was investigated. Experiments were conducted on five fetuses. Sixty-four blood samples from nine hypoxic and recovery periods were analysed. A significant increase of hypoxanthine and lactate occurred in parallel with the fall of arterial oxygen saturation (SaO2) and arterial oxygen pressure (PaO2) during the first 20 min of hypoxia. The elevations in plasma hypoxanthine and lactate were significantly greater during more severe hypoxia than mild hypoxia, as judged from the amount of low oxygen gas mixture given to the ewe (7 or 9%). There were no difference in PaO2 and only minor difference in SaO2 between the two groups. The increase in lactate over 20 min was the same throughout the one-hour period of hypoxia, while the increase of hypoxanthine was less pronounced at the end of the period. This might be due to the fact that hypoxanthine was cleared from fetal plasma at a fairly rapid rate, half of the excess concentration being eliminated after 25 +/- 21 min compared to 85 +/- 47 min for lactate in six experiments post hypoxia. Linear regression analysis revealed a highly significant correlation between hypoxanthine and SaO2, pH and lactate (P less than 0.001). These three variables explained 77% of the variance of hypoxanthine, when calculated by multiple regression analysis.     

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

We aimed to test effects of altitude acclimatization on pulmonary gas exchange at maximal exercise. Six lowlanders were studied at sea level, in acute hypoxia (AH), and after 2 and 8 wk of acclimatization to 4,100 m (2W and 8W) and compared with Aymara high-altitude natives residing at this altitude. As expected, alveolar Po2 was reduced during AH but increased gradually during acclimatization (61 +/- 0.7, 69 +/- 0.9, and 72 +/- 1.4 mmHg in AH, 2W, and 8W, respectively), reaching values significantly higher than in Aymaras (67 +/- 0.6 mmHg). Arterial Po2 (PaO2) also decreased during exercise in AH but increased significantly with acclimatization (51 +/- 1.1, 58 +/- 1.7, and 62 +/- 1.6 mmHg in AH, 2W, and 8W, respectively). PaO2 in lowlanders reached levels that were not different from those in high-altitude natives (66 +/- 1.2 mmHg). Arterial O2 saturation (SaO2) decreased during maximum exercise compared with rest in AH and after 2W and 8W: 73.3 +/- 1.4, 76.9 +/- 1.7, and 79.3 +/- 1.6%, respectively. After 8W, SaO2 in lowlanders was not significantly different from that in Aymaras (82.7 +/- 1%). An improved pulmonary gas exchange with acclimatization was evidenced by a decreased ventilatory equivalent of O2 after 8W: 59 +/- 4, 58 +/- 4, and 52 +/- 4 l x min x l O2(-1), respectively. The ventilatory equivalent of O2 reached levels not different from that of Aymaras (51 +/- 3 l x min x l O2(-1)). However, increases in exercise alveolar Po2 and PaO2 with acclimatization had no net effect on alveolar-arterial Po2 difference in lowlanders (10 +/- 1.3, 11 +/- 1.5, and 10 +/- 2.1 mmHg in AH, 2W, and 8W, respectively), which remained significantly higher than in Aymaras (1 +/- 1.4 mmHg). In conclusion, lowlanders substantially improve pulmonary gas exchange with acclimatization, but even acclimatization for 8 wk is insufficient to achieve levels reached by high-altitude natives.