Effect of iron deficiency on tissue oxygen delivery in cyanotic congenital heart disease

To test the hypothesis that tissue oxygen delivery would be affected by diminished oxygen stores in cyanotic congenital heart disease, serum ferritin, transferrin saturation, hemoglobin, red cell mean corpuscular volume (MCV), red cell 2,3-diphosphoglycerate (DPG), P50, blood gases, oxygen saturations and systemic oxygen transport were measured in 29 hypoxemic infants and children. For the group, aortic saturation was 81 +/- 9%, PaO2 was 50 +/- 12 mm Hg, hemoglobin 16.2 +/- 2.1 gm/dl and systemic oxygen transport 620 +/- 145 ml/min/m2. P50 was increased above normal values (28.8 +/- 2.3 vs 26.6 +/- 1.1 mm Hg, p less than 0.01), and DPG was 2.35 +/- 0.54 mumol/ml, at the upper limits of normal for this assay. Iron deficiency was present in 8. When patients with P50 greater than or equal to 30 mm Hg and P50 less than 30 mm Hg were compared, iron stores were diminished in the high P50 group: [serum ferritin (19 +/- 8 vs 53 +/- 48 ng/ml, p = 0.0006), transferrin saturation (11 +/- 6 vs 23 +/- 11%, p = 0.003) and MCV (79 +/- 8 vs 86 +/- 4 fl, p = 0.05)]. Hemoglobin, aortic oxygen saturation, PaO2 and systemic oxygen transport were similar in both groups. In children with iron sufficiency, 15 of 21 had MCV greater than 90th percentile for age and sex (p less than 0.001 versus expected distribution). Also, MCV greater than 90th percentile for age and sex had a positive predictive value of 0.88 for iron sufficiency. This study demonstrates that diminished iron stores in cyanotic congenital heart disease are associated with a more right-shifted oxyhemoglobin dissociation curve (increased P50).(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased oxyhemoglobin affinity in patients with sleep apnea syndrome

Oxyhemogloblin affinity (P50 at pH 7.4, PaCO2 = 40 mm Hg, temperature = 37 degrees C) and 2,3-DPG concentration were assessed in 15 nonsmokers (14 men and one woman 46 to 63 yr of age) with sleep apnea syndrome (SAS) and in 10 normal subjects (eight men and two women 22 to 48 yr of age). In patients with SAS, mean nocturnal apnea index was 46 +/- 20/h, and mean nocturnal SO2 was 86 +/- 6% versus 94.6 +/- 1.8% during the daytime. Daytime mean P50 of the patients was 28.5 +/- 1.2 mm Hg versus 27.1 +/- 0.3 mm Hg in the normal subjects (p less than 0.05). Daytime mean 2.3-DPG was 1.23 +/- 0.25 moles DPG/mole hemoglobin versus 0.80 +/- 0.15 (p less than 0.05). Significant correlations were found in patients between P50 and mean nocturnal SO2 (r = -0.62, p less than 0.01) and between P50 and 2,3-DPG (r = 0.68, p less than 0.01). The measurements were repeated in five patients after surgical or positive-pressure treatment. P50 and 2,3-DPG both decreased and returned to normal values. In conclusion, the oxyhemoglobin dissociation curve is shifted to the right in patients with SAS and there is an increase in 2,3-DPG. These could be protective mechanisms against the development of polycythemia, pulmonary hypertension, and cor pulmonale.     

Oxyhemoglobin dissociation curve and 2,3-diphosphoglycerate in chronic hypoxemia

The measurement of the oxyhemoglobin dissociation curve (ODC) and 2,3-diphosphoglycerate (2,3-DPG) in patients with chronic hypoxemia is important from the view point of tissue oxygenation. However, there have been no consistent results that explain the relation among chronic hypoxemia, 2,3-DPG and P50, which is oxygen pressure at an oxygen saturation of 50 percent. The aim of this study is to clarify what factors affect P50 and 2,3-DPG. 1) Patients with chronic hypoxemia, who showed PaO2 less than 60 Torr, had significantly higher P50 than normal subjects. 2) The concentration of Hb showed significant negative correlation with both P50 and 2,3-DPG. 3) Arterial blood pH showed significant positive correlation with both P50 and 2,3-DPG. 4) In a group with normal levels of Hb and pH, there was significant negative relationship between PaO2 and P50. 5) In a group with normal levels of Hb and pH, there was significant positive relationship between PaCO2 and P50. 6) In a group with normal levels of Hb, pH and PaCO2, there was significant negative relationship between PaO2 and 2,3-DPG. In conclusion, P50 and 2,3-DPG are affected largely by Hb concentration or blood pH, with or without hypoxemia. However there is a mechanism by which P50 and 2,3-DPG are increased by hypoxemia itself in a group with normal levels of Hb, pH and PaCO2.     

Human red cell age, oxygen affinity and oxygen transport

The [2,3-DPG]/[Hb] ratio and the P50 were found to be lower in the 10% denser (old) than in the 10% lighter (young) red blood cell (RBC) fractions (0.57 +/- 0.13 vs 0.96 +/- 0.13 and 23.02 +/- 0.85 vs 27.47 +/- 1.05 Torr, respectively, mean +/- SD, P less than 0.0005 for both, n = 6). The RBC aging processes appear thus to affect the RBC oxygen affinity. However, the [2,3-DPG] changes do not fully explain the drop of not fully explain the drop of P50 as measured at constant [H+], [CO2] and [HbCO]. It is therefore postulated that an additional factor is involved in the regulation of the oxygen affinity in the ageing RBC. The RBC density in 59 normal individuals matched for age (infants, adult, and aged) and for sex was found to be younger in adult females than in all other groups (P less than 0.0005), including an age-matched group of pregnant women. Correspondingly, the [2,3-DPG]/[Hb] ratio and the P50 are higher in adult females than in adult males (0.92 +/- 0.10 vs 0.82 +/- 0.09, P less than 0.009, and 29.03 +/- 1.07 vs 27.72 +/- 0.82 Torr, P less than 0.002, respectively). These data are evaluated in terms of the efficiency of the oxygen transport calculating the circulatory load required to transport a given amount of oxygen to the tissues. The results indicate that the lower oxygen affinity (due to the younger RBC population) in adult females partially compensates for their lower [Hb].     

Theophylline clearance in patients with severe chronic obstructive pulmonary disease receiving supplemental oxygen and the effect of acute hypoxemia

The effect of hypoxemia on the disposition of theophylline was examined in 10 stable patients with chronic obstructive pulmonary disease (COPD) receiving chronic theophylline and supplemental home oxygen therapy. Pharmacokinetics after intravenous theophylline were estimated on the second day of supplemental oxygen (PaO2, 69 +/- 4 mmHg; mean +/- SEM) and on the second day of room air breathing (PaO2, 43 +/- 3) using a randomized cross-over design. On each occasion stable isotope-enriched theophylline (10 mg, m/z 183) was administered intravenously along with the regular oral dose of theophylline (m/z 180). Concentrations of both forms of theophylline in plasma samples obtained over 24 h were measured using mass spectrometry. Theophylline clearance during oxygen therapy (0.048 +/- 0.005 L/h/kg) was similar to that during room air breathing (0.050 +/- 0.004 L/h/kg). Values for elimination half-life (7.6 +/- 0.8 versus 6.8 +/- 0.6 h) and volume of distribution at steady state (0.450 +/- 0.021 versus 0.429 +/- 0.024 L/kg) were also unchanged. The volume of distribution of theophylline was inversely related to arterial pH during oxygen therapy (pH range, 7.32 to 7.44) and during room air breathing (pH range, 7.33 to 7.47). Although hypoxemia does not alter theophylline clearance in patients with COPD, theophylline loading doses may need adjustment according to arterial pH because of an effect on volume of distribution.     

Control of oxygen affinity of hemoglobin in K562 cells induced by hemin

The oxygen affinity of hemoglobin in K562 cells induced by hemin and the relationship between levels of 2,3-diphosphoglycerate (2,3-DPG) and hemoglobin have been investigated. Absorption spectra of induced cells indicate that the hemoglobin is oxygenated; oxygen dissociation curves are symmetric, with a P50 of 20 +/- 0.9 mm Hg, Hill coefficient of 2.5, and a normal temperature dependence. The intracellular pH measured by phosphorus 31 nuclear magnetic resonance (NMR) was 7.3. The amount of 2,3-DPG was determined by an enzymatic method and by 31P NMR. The level of 2,3-DPG in uninduced K562 cells, containing 0.5 pg of hemoglobin per cell, was low (5 +/- 0.5 mumole/10(8) cells), but increased to 64 +/- 5 mumole/10(8) cells upon induction of hemoglobin accumulation (to a final level of 20 pg hemoglobin/cell). For several experiments, there was a closely coordinated relationship between 2,3-DPG and hemoglobin levels, at about 1:1 stoichiometry of the two molecules. The time course of induction of hemoglobin, and of 2,3-DPG levels, are very similar; both processes are reversible. These data suggest that induction of hemoglobin synthesis in K562 cells by hemin results in hemoglobin-containing cells with normal oxygenation properties and that 2,3-DPG and hemoglobin levels are coordinately controlled in these cells. Elucidation of the mechanism of this effect should be of importance in understanding the erythroid-like differentiation of these cells.     

Comparing supplementary oxygen benefits from a portable oxygen concentrator and a liquid oxygen portable device during a walk test in COPD patients on long-term oxygen therapy

BACKGROUND: Differences in oxygen delivery between portable oxygen concentrators (POC) and liquid oxygen (LO) portable units, pose a question if POCs are equally effective as LOs in reducing exercise-induced hypoxaemia. DESIGN: Randomized, single-blind clinical trial. PATIENTS: Thirteen COPD patients (means: age 66+/-11 year, FEV(1) 35.2+/-13.7% predicted) and respiratory failure (means: PaO2 52+/-5mmHg, PaCO2 51.3+/-7.5mmHg). METHODS: All patients underwent a series of 6-min walk tests (6MWT) carried out in random order among one of the three devices: POC, LO cylinder and cylinder with compressed air (CA). Oxygen supplementation was 3lpm for LO and an equivalent to 3lpm in a pulse flow system for POC. RESULTS: The mean SpO2 was equally improved at rest: 92.9+/-2.8% with POC and 91.7+/-2.0% with LO compared to CA-87.8+/-2.7% (POC and LO vs. CA p<0.05). POC and LO significantly improved oxygenation during 6MWT (mean SpO(2) was 84.3+/-5% and 83.8+/-4.2%, respectively) compared to breathing CA-77.6+/-7.4%, p<0.05. Mean 6MWT distance increased with LO (350+/-83m) and POC (342+/-96m) when compared to CA (317+/-84m), however, these differences were not statistically significant. Dyspnoea score assessed at the end of the exercise (Borg scale) was significantly lower when breathing oxygen (4.2+/-1.2 with POC and 4.1+/-1.7 with LO vs. 5.4+/-1.9 with CA, p<0.05). CONCLUSIONS: Effectiveness of oxygen supplementation from a POC did not differ from the LO source during 6MWT in COPD patients with respiratory failure. Oxygen at 3lpm flow was not sufficient to prevent hypoxaemia during strenuous exercise.     

Importance of oxygen-haemoglobin binding to oxygen transport in congestive heart failure.

OBJECTIVE--To assess the importance of 2,3-diphosphoglycerate (2,3-DPG) and oxygen-haemoglobin binding to oxygen transport in patients with congestive heart failure. METHODS--In 30 patients with severe congestive heart failure, arterial, mixed venous, and coronary sinus venous blood concentrations of 2,3-DPG were measured and systemic output and coronary sinus blood flow were measured by a thermodilution technique. Oxygen-haemoglobin affinity was expressed as the oxygen tension in mm Hg at which blood is 50% saturated with oxygen (P50). RESULTS--Compared with normal values, 2,3-DPG was high in arterial blood (2.58 mumol/ml, p = 0.01; 20.8 mumol/g haemoglobin, p < 0.0001). Significant gradients between arterial, mixed venous, and coronary sinus blood 2,3-DPG concentrations were also found (mixed venous = 2.40 mumol/ml, p = 0.05 v arterial blood; coronary sinus venous blood = 2.23 mumol/ml, p < 0.04 v arterial blood). P50 was correspondingly high compared with the accepted normal value (mean 29.7 mm Hg, normal 26.6 mm Hg, p < 0.001). Systemic oxygen transport (351 ml O2/min/m2) varied directly with the forward cardiac index (r = 0.89, p < 0.0001). There was no relation between systemic oxygen transport and arterial oxygen content. Similarly, myocardial oxygen transport was found to vary directly with coronary sinus blood flow. Calculations of changes in cardiac index and coronary sinus blood flow at normal oxygen-haemoglobin binding indicate that a considerable increase in cardiac index and coronary blood flow would be required to maintain similar systemic and myocardial oxygen transport. CONCLUSIONS--In patients with severe heart failure increased 2,3-DPG and reduced oxygen-haemoglobin binding may be compensatory mechanisms that maintain adequate systemic and delivery of oxygen to myocardial tissue.     

Red cell 2,3-diphosphoglycerate and oxygen affinity of hemoglobin in patients with thyroid disorders

We measured red blood cell 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP), and the P50 value in vitro of the oxyhemoglobin dissociation curve, which is the oxygen tension at half saturation of hemoglobin, in order to quantitate red blood cell oxygen transport function in individuals who were diagnosed as hypothyroid, euthyroid, or hyperthyroid based on measurements of thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), and their clinical status. Hypothyroid (mean T4 2.8 microgram/dl, T3 49 ng/dl, TSH 37 microU/ml) and hyperthyroid (mean T4 14 microgram/dl, T3 271 ng/dl, TSH less than 0.7 microU/ml) patients had normal red cell 2,3-DPG and ATP levels and normal P50 values in vitro. The known changes in oxygen consumption produced by alterations in thyroid hormone levels in patients with hypothyroidism or hyperthyroidism did not affect red blood cell oxygen transport function.     

Noninvasive positive-pressure ventilation vs. conventional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy

OBJECTIVE: We have reported previously on the use of noninvasive positive-pressure ventilation (NPPV) to assist spontaneous breathing in high-risk hypoxemic patients (i.e., PaO(2)/fraction of inspired oxygen [FIO(2)] ratio, < or = 100) who are undergoing diagnostic fiberoptic bronchoscopy (FOB). The efficacy of this intervention in patients with less severe forms of hypoxemia (i.e., PaO(2)/FIO(2) ratio, < 200) is unknown. PATIENTS AND METHODS: Twenty-six patients with PaO(2)/FIO(2) ratios < or = 200 who required bronchoscopic BAL for suspected nosocomial pneumonia were entered into the study. Thirteen patients were randomized during FOB to receive NPPV, and 13 patients were randomized to receive conventional oxygen supplementation by Venturi mask. The primary end points were changes in the PaO(2)/FIO(2) ratio during FOB and within 60 min of terminating the procedure. RESULTS AND OUTCOME: At study entry, the two groups were similar in terms of age, simplified acute physiologic score II values, and cardiorespiratory parameters. During FOB, the mean (+/- SD) PaO(2)/FIO(2) ratio increased by 82% in the NPPV group (261 +/- 100 vs 139 +/- 38; p < 0.001) and decreased by 10% in the conventional oxygen supplementation group (155 +/- 24 to 139 +/- 38; p = 0.23). Sixty minutes after undergoing FOB, the NPPV group had a higher mean PaO(2)/FIO(2) ratio (176 +/- 62 vs 140 +/- 38; p = 0.09), a lower mean heart rate (91 +/- 18 vs. 108 +/- 15 beats/min; p = 0.02), and no reduction in mean arterial pressure in comparison to a 15% decrease from the baseline in the control group. One patient in the NPPV group and two patients in the control group required nonemergent intubation. Major bacterial isolates included Staphylococcus aureus (7 of 30 isolates; 23%) and Pseudomonas aeruginosa (12 of 30 isolates; 40%). CONCLUSION: In patients with severe hypoxemia, NPPV is superior to conventional oxygen supplementation in preventing gas-exchange deterioration during FOB with better hemodynamic tolerance.     

Effect of oxygen administration on the breathing pattern during haemodialysis in man

During haemodialysis (HD), allowing important CO2- unloading, an irregular breathing pattern (BP) is frequently observed. This has been attributed to a decrease in central chemoreceptor firing, with a greater contribution of the peripheral chemoreceptors in the chemical drive to breathe. To provide further evidence for these findings we studied five patients with end-stage renal failure in chronic HD. They underwent HD with a cuprophane membrane and acetate-containing dialysate. Ventilation was measured continuously using respiratory inductance plethysmography. Oxygen was administered for 30 min, using nasal cannulae, at a rate of 6 l.min-1, starting 130 min after the onset of the HD. Blood gases were taken from the arterial line. During the initial air breathing, arterial oxygen tension (PaO2) decreased from 12.3 +/- 1.2 kPa (92.8 +/- 8.9 mmHg) at 0 min to 10.5 +/- 1.8 kPa (79.0 +/- 13.3 mmHg) at 2 h (p less than 0.01) (mean +/- SD). All patients showed irregular breathing with 1.4 +/- 0.6 apnoeas exceeding 10 s per 10 min after 2 h. Minute ventilation decreased from 6.8 +/- 1.9 l.min-1 at 0 min to 5.4 +/- 1.3 l.min-1 at 2 h (p less than 0.05). During the O2 breathing, PaO2 increased to 26.3 +/- 4.0 kPa (197.8 +/- 30.3 mmHg) (p less than 0.001), while arterial carbon dioxide tension (PaCO2) remained unchanged. The irregular BP previously observed vanished completely. The mean number of apnoeas exceeding 10 s per 10 min decreased to 0.08 +/- 0.12 during O2 (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of dilazep on hemoglobin-oxygen affinity in patients with ischemic heart disease

The effects of orally administered dilazep, an antianginal drug, on the hemoglobin-oxygen affinity were studied in 31 cases with ischemic heart disease. Prior to medication, the mean P50 value was 29.2 +/- 1.65 mmHg. There were no significant differences in the P50 value according to the age of patient or the severity of the coronary arterial disease. Acute effects of dilazep were studied in 29 patients. The 30 min and 60 min post-administration P50 values increased significantly to 30.2 +/- 2.55 mmHg and 30.4 +/- 2.31 mmHg, respectively. Eight patients were administered 300 mg of oral dilazep daily for 4 weeks. Three of 4 in whom exercise tolerance improved showed increases in P50. No changes in various factors which might affect the P50 value, including 2,3-DPG, were found.     

Oxygen dissociation curves in children with anemia and malignant disease

Two automatic apparatuses utilizing a dual wavelength spectrophotometer were used to perform oxygen dissociation curves on microsamples of blood. The method provides a complete print-out of an oxygen dissociation curve in 15--20 min and the P50 vlues obtained in normal individuals agree closely with those obtained by classical methods. These apparatuses were used to measure oxygen affinity, ie P50, in anemic children with malignant disease prior to treatment and in children undergoing therapy. Red cell 2,3-DPG levels were also measured. In patients with anemia at the time of diagnosis and prior to therapy, the P50 values and 2,3-DPG levels were elevated as is usual in other types of anemia. However, when oxygen affinity and 2,3-DPG levels were measured in anemic patients receiving treatment, three types of response to anemia were noted: 1) increased P50 and 2,3-DPG; 2) normal or low P50 and 2,3-DPG, and; 3) normal or low P50 with increased 2,3-DPG. Patients who adapted poorly to anemia during treatment had usually received prior intensive chemotherapy and transfusion therapy, and their pattern of red cell glycolytic intermediates was consistent with a red cell population with an increased cell age. The failure of some patients to respond to anemia with a decrease in oxygen affinity has implications in regards to the hemoglobin level at which they should be transfused.     

Almitrine improves oxygenation when both awake and asleep in patients with hypoxia and carbon dioxide retention caused by chronic bronchitis and emphysema

Patients with chronic bronchitis and emphysema who are hypoxic when awake become more hypoxic during sleep, with a further rise in their preexisting pulmonary hypertension. Almitrine, a respiratory stimulant, improves arterial blood gas tensions in such patients when they are awake. We have used a double-blind, placebo-controlled, cross-over study to compare the effects of 50 mg almitrine given orally twice a day for 14 days on oxygen saturation (SaO2), respiratory movements, and sleep quality in 9 patients with hypoxic chronic bronchitis and emphysema (FEV1, 0.4 to 1.0 L; PaO2, 51 +/- (SEM) 2 mmHg; PaCO2, 49 +/- 1 mmHg). Almitrine improved arterial blood gas tensions when awake, mean PaO2 rising by 8 mmHg (p less than 0.001) and PaCO2 falling by 4 mmHg (p less than 0.01). Almitrine improved nocturnal oxygenation, mean SaO2 when awake rising from 83 +/- 4% to 89 +/- 3% (p less than 0.01), and the lowest SaO2 during sleep rising on average from 65 +/- 6% to 77 +/- 3% (p less than 0.02). The number of hypoxemic episodes (SaO2 falling by greater than or equal to 10% from the preceding stable baseline during sleep) and the time when SaO2 was below 80% (135 +/- 53 versus 46 +/- 35 min; p less than 0.01) also improved. Almitrine did not improve sleep quality. We conclude that almitrine improves arterial gas tensions when awake and reduces the frequency and severity of nocturnal hypoxemia without impairing sleep quality in patients with chronic bronchitis and emphysema who are both hypoxemic and hypercapnic when awake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence of nocturnal desaturation while breathing oxygen in COPD patients undergoing long-term oxygen therapy

STUDY OBJECTIVE: It is suggested that oxygen flow be increased by 1 L/min during sleep in COPD patients undergoing long-term oxygen therapy (LTOT) in order to avoid nocturnal desaturations. The purpose of this study was to investigate the occurrence of nocturnal desaturations while breathing oxygen in COPD patients receiving LTOT. SETTING: Inpatient/university hospital. PATIENTS: We studied 82 consecutive COPD patients. Their functional characteristics were as follows (mean +/- SD): FVC, 2.15 +/- 0.69 L; FEV(1), 0.87 +/- 0.33 L; PaO(2), 51.6 +/- 5 mm Hg; and PaCO(2), 47 +/- 8 mm Hg. MEASUREMENTS: Overnight pulse oximetry (PO) was performed twice: (1) while breathing air and (2) while breathing supplemental oxygen assuring satisfactory diurnal resting oxygenation (mean PaO(2) during oxygen breathing, 67 +/- 6 mm Hg; mean arterial oxygen saturation [SaO(2)] during oxygen breathing, 93%). RESULTS: PO performed while patients were breathing air showed a mean overnight SaO(2) of 82.7 +/- 6.7%. Patients spent 90% of the recording time with an SaO(2) of < 90%. While breathing oxygen, 43 patients (52.4%) remained well oxygenated. Their mean overnight SaO(2) while breathing oxygen was 94.4 +/- 2.1%, and time spent with saturation < 90% was 6.9 +/- 8.6%. Thirty-nine patients (47.6%) spent > 30% of the night with an SaO(2) of < 90% while breathing supplemental oxygen. Their mean overnight SaO(2) while breathing oxygen was 87.1 +/- 4.5%, and time spent with an SaO(2) of < 90% was 66.1 +/- 24.7% of the recording time. Comparison of ventilatory variables and daytime blood gases between both groups revealed statistically significantly higher PaCO(2) on air (p < 0.001) and on oxygen (p < 0. 05), and lower PaO(2) on oxygen (p < 0.05) in the group of patients demonstrating significant nocturnal desaturation. CONCLUSIONS: We conclude that about half of COPD patients undergoing LTOT need increased oxygen flow during sleep. Patients with both hypercapnia (PaCO(2) > or = 45 mm Hg) and PaO(2) < 65 mm Hg while breathing oxygen are most likely to desaturate during sleep.     

Pharmacologic elevation of blood inorganic phosphate in hypoxemic patients with COPD

We have shown that in patients with COPD, myocardial efficiency during exercise is enhanced following acute elevations of plasma phosphate (Pi). A decrease in Hb-O2 affinity (increase in P50) was not responsible for the improvement. We postulated that the physiologic benefit was due to the acute reversal of a subclinical myocardial Pi depletion. To further test this hypothesis in a chronic state, we studied nine stable hypoxemic (PaO2 = 64 +/- 2 mm Hg [+/- SEM]) patients with COPD over five weeks: two weeks at normal plasma Pi; and three weeks at elevated plasma Pi, induced by etidronate disodium (Didronel; 750 mg orally daily). Administration of etidronate disodium increased (p less than 0.05) plasma level of Pi (4.4 +/- 0.2 to 5.8 +/- 0.1 mg/dl), RBC level of Pi (3.1 +/- 0.2 to 4.1 +/- 0.2 mg/dl), RBC level of 2,3-DPG (16.2 +/- 1.1 to 21.3 g+/- 1.3 mumol/g of Hb) and P50 (23.7 +/- 0.5 to 26.0 +/- 0.8 mm Hg). At the end of the treatment, the widening of the C(a-v)O2 with exercise (7.1 +/- 0.8 to 8.9 +/- 0.6 ml/dl) was less pronounced than under control conditions (6.9 +/- 0.4 to 10.1 +/- 0.6 ml/dl; p less than 0.02); concomitantly, the crossover point (COP; the PaO2 below which a rightward-shifted Hb-O2 curve causes the C(a-v)O2 to become narrower rather than wider) increased (37 +/- 2 to 49 +/- 1 mm Hg). Indicators of myocardial work efficiency were not affected by etidronate disodium at rest or during exercise. We postulate that during exercise the potential beneficial effect of the rightward shift of the Hb-O2 curve upon cardiac function was negated by the fall of PaO2 to or below the COP level, a situation which would limit increases in tissue O2 extraction.     

Treatment of chronic respiratory failure in kyphoscoliosis: oxygen or ventilation?

Patients with kyposcoliosis and chronic respiratory insufficiency are treated either with home oxygen therapy or ventilation. Kyphoscoliotic patients demonstrate impaired ventilatory mechanics, consequently ventilation seems to be the treatment of choice. Yet, no randomised controlled trials (CRT) exist to prove it. Most investigators find it difficult to ethically justify a CRT. Therefore, the current authors performed the following retrospective study: survival and pulmonary function were analysed in all consecutive kyphoscoliotic patients who started long-term oxygen therapy (LTO group; n=15, aged 62+/-11 yrs (mean+/-SD)) or LTO plus nocturnal nasal intermittent positive pressure ventilation (nNIPPV group; n=18, aged 61+/-7 yrs) in the Dept of Pulmonology (University Hospital Gasthuisberg, Leuven) between 1990-2002. Prior to treatment partial pressure of oxygen (PO2) was lower, partial pressure of carbon dioxide (PCO2) tended to be higher and vital capacity (VC) tended to be lower in the nNIPPV group than in the LTO group (PO2 5.9+/-1 versus 6.7+/-0.9 kPa (44+/-8 versus 50+/-7 mmHg), PCO2 8+/-1 versus 7.3+/-0.9 kPa (60+/-8 versus 55+/-7 mmHg), VC 32+/-12 versus 40+/-16% predicted, or 645+/-244 versus 970+/-387 mL). In the nNIPPV group the 1-yr survival was higher (100% versus 66%). nNIPPV patients demonstrated an improvement in PO2 (breathing air) +54%, PCO2 (breathing air) -21%, VC +47% and maximal static inspiratory mouth pressure +33%; these improvements were absent in the LTO group. In conclusion, nocturnal nasal intermittent positive pressure ventilation, plus long-term oxygen therapy results in more favourable survival and changes in blood gases and respiratory function than long-term oxygen therapy alone.     

Systemic oxygen transport in patients with congenital heart disease

The physiology of oxygen delivery was studied in 118 stable patients from 3 months to 20 years old with congenital heart disease. During cardiac catheterization, oxygen consumption (VO2), arterial and venous blood gases and oxygen saturations (range 41% to 98%), hemoglobin concentration, diphosphoglycerate (2,3-DPG), and P50 levels were measured, and then cardiac output, systemic oxygen transport (SOT), arterial and venous oxygen contents, and the VO2/SOT ratio (fractional O2 extraction) were calculated. P50 averaged 31 mm Hg, compared with 27 mm Hg in 10 control children (p less than .01). The composite O2-hemoglobin dissociation curve in vivo was broad: Po2 varied from 37 to 65 mm Hg at 80% saturation. P50, 2,3-DPG, hemoglobin concentrations, and O2 saturation varied widely and inconsistently with Po2 and arterial and venous O2 content, but resulted in clustering of the arterial oxygen content near 165 +/- 23 (SD) ml/liter over a wide range of Po2 and hemoglobin concentrations. SOT varied in direct relation with flow (r = .82, p less than .001), but not with oxygen content, Po2, or P50. VO2 varied widely at normal or high levels of SOT, but decreased linearly at SOT levels below 400 ml/min/m2. Oxygen extraction varied inversely with venous O2 content, rising to about 50% and plateauing below venous contents of 100 ml/liter. O2 extraction did not correlate with Po2, arterial O2 content, or P50. These data suggest that: O2 saturation cannot be predicted or calculated accurately from measured Po2, but must be measured directly, 2,3-DPG, hemoglobin concentration, and P50 fluctuate to stabilize arterial oxygen content, SOT is determined primarily by cardiac output in subjects who are adapted chronically, O2 extraction rises, due to a fall in venous O2 content, to maintain VO2 as transport falls, below a critical level of SOT, O2 extraction ceases to rise and VO2 falls with further reduction in transport.     

Respiratory characteristics of blood from Basenji dogs with classical erythrocyte pyruvate kinase deficiency.

The oxygen affinities of blood from eight Basenji dogs homozygous for classical erythrocyte pyruvate kinase deficiency and four dogs heterozygous for the defect were compared with blood from 14 Labrador retrievers and two normal Basenji dogs. The homozygous dogs showed significant anemia compared to heterozygous and normal dogs (P is less than 0.01). The average blood P50 value (at 38C and plasma pH of 7.40) for both homozygous and heterozygous dogs was significantly higher (P is less than 0.01) than for normal dogs (33.6+/-0.4 and 31.8+/-0.7 vs 30.8+/-0.6 mm Hg). The concentrations of 2,3-DPG in the blood of both heterozygous and homozygous dogs were significantly higher than normal values. Four months after splenectomy P50 values declined to normal in four homozygous Basenji dogs without any change in the degree of anemia or blood 2,3-DPG concentrations. Iron kinetic studies showed a shorter plasma clearance time in a homozygous than in a normal dog with the heterozygote falling midway between. The red cell life span in the normal and heterozygous dogs was approximately 120 days. The 59Fe studies on the homozygous dog indicate markedly different survival characteristics which can be attributed to the existence of three populations of red cells differing in their life spans.     

Effect of oxygen on sleep and breathing in patients with interstitial lung disease at moderate altitude.

OBJECTIVE: To investigate the impact of oxygen on sleep and breathing in patients with interstitial lung disease (ILD) in Mexico City, at 2,240 m of altitude. PARTICIPANTS: Nineteen ILD patients with a mean FVC of 58 +/- 17% pred. (SD) and a mean PaO(2) of 51 +/- 6 mm Hg were recruited from a pulmonary clinic in a tertiary referral center. In addition, 14 normal control subjects, matched for age and gender, were studied. All patients underwent two consecutive full polysomnographies (PSG), one breathing room air and one breathing supplementary oxygen through nasal prongs, in random order. Controls were studied for one night breathing room air. RESULTS: The mean oxygen saturation (SaO(2)) in ILD patients was 82.3 +/- 9.1% during sleep on air and 94.8 +/- 2.9% on oxygen (p < 0.001). In controls it was 92.9 +/- 1.9% (p < 0.001). Sleep efficiency was similar in patients and controls (75 vs. 82%, p > 0.05) and did not change with oxygen (77%). Arousal index was 12.4 +/- 6.9.h(-1) in ILD patients breathing room air and 12.9 +/- 9.1.h(-1) breathing oxygen while in controls it was 11.4 +/- 5.4.h(-1). Breathing frequency (f) during sleep was 24.7 +/- 4.2 in ILD patients and decreased breathing oxygen to 22.5 +/- 3.6 (p < 0.001) but was still higher than in controls (15.6 +/- 2.7; p < 0.001). Similarly, the heart rate (HR) in ILD and controls was 79 +/- 12 and 68 +/- 8, respectively (p < 0.001), and decreased to 68 +/- 4 when patients breathed oxygen (p < 0.001). CONCLUSIONS: Oxygen substantially decreases HR and f, but does not normalize the f in ILD patients. The impact of hypoxia on sleep efficiency and arousal index was not demonstrable in our patients acclimatized to moderate altitude.