Effect of hypoxemia on sodium and water excretion in chronic obstructive lung disease.

To determine the role of hypoxemia in the pathogenesis of impaired sodium and water excretion in advanced chronic obstructive lung disease, 11 clinically stable, hypercapneic patients requiring long-term supplemental oxygen were studied. The renal, hormonal, and cardiovascular responses to sodium and water loading were determined during five-and-a-half-hour studies on a control day (arterial oxygen tension = 80 +/- 6 mm Hg) and on an experimental day under hypoxic conditions (arterial oxygen tension = 39 +/- 2 mm Hg). Hypoxemia produced a significant decrease in urinary sodium excretion but did not affect urinary water excretion. Hypoxemia also resulted in concomitant declines in mean blood pressure, glomerular filtration rate, and filtered sodium load. Renal plasma flow and filtration fraction were unchanged whereas cardiac index rose. On the control day, plasma renin activity and norepinephrine levels were elevated whereas aldosterone and arginine vasopressin levels were normal; none of these four hormones was affected by hypoxemia. Renal tubular function did not appear to be altered by hypoxemia as there was no significant change in fractional reabsorption of sodium. The concurrent decreases in glomerular filtration rate, filtered sodium load, and mean blood pressure at constant renal plasma flow suggest that the reduction in urinary sodium excretion was due to an effect of hypoxemia on glomerular function, possibly related to impaired renovascular autoregulation.

The effect of oxygen on sodium excretion in hypoxemic patients with chronic obstructive lung disease.

In advanced chronic obstructive lung disease (COLD), sodium retention is common, associated with reduction in renal plasma flow (RPF) and stimulation of the renin-aldosterone (PRA-PA) system, two abnormalities due to or influenced by hypercapnia: the independent role of hypoxemia in perturbing sodium homeostasis is unknown. In five stable patients with COLD (FEV1 = 0.9 +/- 0.21, mean +/- SE) with mild edema, during two weeks of a low sodium diet (one week on room air: pH = 7.39 +/- 0.02; PaO2 = 55 +/- 4 mm Hg; PaCO2 = 49 +/- 4 mm Hg; and one week on O2: pH = 7.38 +/- 0.01; PaO2 = 72 +/- 6 mm Hg; PaCO2 = 52 +/- 4 mm Hg) we monitored sodium balance, systemic and renal hemodynamics, plasma sodium and potassium, PRA, PA, and atrial natriuretic hormone (ANH). During air breathing, patients uniformly showed a depression of RPF despite normal cardiac output; plasma hormone levels did not differ from controls but there was elevation (greater than 2 SD above the normal mean) of PRA in four patients, PA in two patients, and ANH in two of five patients. During O2 breathing, urinary sodium increased significantly from 67 +/- 7 to 102 +/- 10 mEq/24 h. Surprisingly, the patients experienced a small but significant weight gain (0.6 +/- 0.1 kg). None of the other variables was affected by O2 therapy. The following conclusions were reached: in advanced COLD, correction of hypoxemia results in sodium diuresis, indicating that hypoxemia (in the presence of hypercapnia) contributes to sodium retention. The mechanism for this beneficial effect of O2 will require further investigation.

Oxygen may lower the O2 cost of ventilation in chronic obstructive lung disease.

It is known that the O2 COV in COLD is high; O2 administration to these patients lowers airway resistance, a major determinant of the COV. Thus, O2 should lower the COV. We measured the COV in ten stable COLD patients and five normal control subjects breathing room air and 30 percent O2. Results indicate that the COV of our patients was elevated above that of control subjects, was related to disease severity, and was decreased with 30 percent O2. The COV of control subjects also was lowered by O2. At rest, O2 lowered VE, VEQ O2 and HR. During submaximal exercise O2 lowered VE, reduced VEQ O2 and extended total exercise time. An inverse correlation was noted between COV and maximal O2 uptake. Thus, in stable COLD, the COV is elevated in proportion to the degree of airway obstruction, inversely related to exercise capacity and lowered by O2 administration.

Metabolic basis for inspiratory muscle fatigue in normal humans.

Inspiratory muscle fatigue, a common event in patients in the intensive care unit, is under multifactorial control. To test the hypothesis that systemic oxygenation is a factor in this event, we subjected five healthy males (age 42 +/- 3 yr) to continuous inspiratory pressure (75% of maximal inspiratory pressure, -95 +/- 5 cmH2O) with the use of a controlled breathing pattern while they breathed normoxic (21% O2), hyperoxic (30% O2), and hypoxic (13% O2) mixtures. Inspiratory muscle endurance (IME; time that pressure could be maintained) and other cardiorespiratory parameters were monitored. Room air IME (3.3 +/- 0.4 min) was shortened (P < 0.05) during 13% O2 breathing (1.6 +/- 0.4 min) but was unaffected during 30% O2 breathing (4.0 +/- 0.6 min). Inspiratory loading lowered the respiratory exchange ratio (RER) during the 21 and 30% O2 trials (1.02 +/- 0.01 to 0.80 +/- 0.03% and 1.05 +/- 0.05 to 0.69 +/- 0.01%, respectively) but not during the 13% O2 trials (1.03 +/- 0.03 to 1.06 +/- 0.07%). At the point of fatigue during the 13% O2 trials, RER was lower compared with the same time point during the 21 and 30% O2 trials. A significant relationship was observed between IME and RER (r = -0.73, P = 0.002) but not between IME and any of the other measured variables. We conclude that 1) hypoxemia impairs the ability of the inspiratory muscles to sustain a mechanical challenge and 2) substrate utilization of the respiratory muscles shifts toward a greater reliance on lipid metabolism when O2 is readily available; this shift was not observed when the O2 supply was reduced.

Pleural fluid and serum eosinophilia: association with fluoxetine hydrochloride.

We report the case of a patient who was treated with fluoxetine hydrochloride (Prozac) for depression. Approximately 8 weeks into the treatment, an eosinophilic pleural effusion and serum eosinophilia developed. An extensive workup for the etiology of eosinophilic pleural effusion was unrevealing. Pleural biopsy showed a nonspecific inflammatory reaction and mild fibrosis. The pleural effusion and eosinophilia resolved within a few weeks of cessation of the drug. Fluoxetine can be associated with pleural and serum eosinophilia, possibly through an allergic-mediated reaction.

Arterialized ear lobe blood samples for blood gas tensions.

The accuracy of arterialized blood samples both at rest and during exercise is described in comparison to simultaneous arterial blood samples. The technique was found to be reliable and sufficiently accurate for clinical exercise testing, with no significant differences for Po2 or Pco2 between the two methods.

An analysis of submaximal exercise responses in patients with sarcoidosis and fibrosing alveolitis.

An increase work rate exercise test was performed by 15 patients with sarcoidosis and by 20 patients with fibrosing alveolitis. The patients with sarcoidosis had a moderate reduction in total lung capacity (TLC) and transfer factor (DLCO), with chest radiographs showing widespread pulmonary infiltration but no evidence of fibrosis. The patients with fibrosing alveolitis had a significantly greater reduction in TLC and DLCO than those in the sarcoidosis group. Values for cardiac frequency (fH) and ventilation(V) were interpolated to the standard oxygen uptakes of 0.75, 1.0 and, where possible, 1.5 litres/min (33.5, 44.6 and 67 mmol/min respectively). The tidal volume at the ventilation of 20 and 30 litres/min was also determined. The exercise responses were compared to two groups of 20 normal men; each group being age matched to one group of patients. The fH at oxygen uptakes of 0.75, 1.0 and 1.5 litres/min were significantly higher in both patient groups than in the normal men. The submaximal indices for V were significantly greater in both patients groups than in the normal subjects at all three levels of oxygen uptake, and significantly greater in patients with fibrosing alveolitis than in those with sarcoidosis. The tidal volumes at 20 and 30 litres/min were smaller than normal in both patient groups but differences were removed by normalizing for differences in vital capacity. The maximum exercise ventilation measured in the patients with fibrosing alveolitis was significantly correlated with measurements of lung volume. Submaximal indices detect significant abnormalities during exercise in patients with pulmonary fibrosis and represent an alternative method for documenting abnormal exercise responses. Despite comparable radiological abnormalities the functional impairment in fibrosing alveolitis is much greater than in sarcoidosis. Thus the physiological abnormalities are not comparable quantitatively although they share a common qualitative difference.

Evidence for abnormal regulation of circulating 1 alpha, 25-dihydroxyvitamin D in patients with pulmonary tuberculosis and normal calcium metabolism.

Available evidence indicates that hypercalcemia in pulmonary tuberculosis results from increases in circulating 1 alpha, 25-dihydroxyvitamin D [1 alpha, 25(OH)2D]. To further characterize vitamin D metabolism in this disorder, the effects of vitamin D, 100,000 units a day for 4 days, were compared in 25 normal subjects and 11 patients with active pulmonary tuberculosis who were normocalcemic and had not had hypercalcemia. Serum calcium, phosphorus, 25-hydroxyvitamin D (25-OHD) and 1 alpha, 25(OH)2D were measured. Whereas vitamin D increased mean serum 25-OHD from 20 +/- 2 (+/- SE) to 40 +/- 5 ng/ml (P less than 0.001) and did not change mean serum 1 alpha, 25(OH)2D in the normals (33 +/- 2 vs. 31 +/- 2 pg/ml), it increased mean serum 25-OHD from 21 +/- 4 to 55 +/- 13 ng/ml (P less than 0.05) and mean serum 1 alpha, 25(OH)2D from 28 +/- 2 to 35 +/- 3 pg/ml (P less than 0.05) in the patients. Serum calcium was normal and remained within the normal range in all subjects and patients. The findings indicate that there is a modest but significant abnormality in the regulation of circulating 1 alpha, 25(OH)2D in normocalcemic patients with pulmonary tuberculosis. The results are similar to those previously reported by us in normocalcemic patients with sarcoidosis.

The effect of acute exercise on natural killer-cell activity of trained and sedentary human subjects.

The effect of acute exercise on natural killer (NK) activity and on the distribution of phenotypic characteristics of peripheral blood lymphocytes was examined. Trained and sedentary individuals underwent a standard progressive exercise test on a cycle ergometer using an incremental work load of 15 W (90 kpm), increased every minute. Each subject was encouraged to exercise to exhaustion, and total ventilation and mixed expired O2 and CO2 were measured every 30 sec. All subjects reached the "anaerobic" threshold as judged by the deflection of ventilation at a work load near VO2max. NK activity against K562 reached maximum levels immediately after exercise, dropped to a low point 120 min later, then slowly came back to preexercise levels within 20 hr. No significant differences were observed between the trained and the sedentary groups. Furthermore, immediately after exercise the proportion of OKT-3+ and OKT-4+ cells was reduced by 29.8 +/- 3.6 and 33.6 +/- 5.4%, respectively; the percentage Leu-7+ and Leu-11a+ cells was increased by 53.9 +/- 1.7 and 57.3 +/- 2.9%, respectively. The percentage OKT-8+ cells was not significantly altered. When the percentage binding of effector to target cells was examined, it was highest at 0 min post-exercise (19 +/- 6.2%) and lowest at 120 min postexercise (7 +/- 3.9%), but the absolute number of NK cells remained unchanged. The source of serum used in the lytic assay had no effect on the NK activity, as fetal calf serum and autologous sera drawn at different time intervals during exercise gave similar results.(ABSTRACT TRUNCATED AT 250 WORDS)