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.

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.

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)

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.

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.

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.