Comparison of oxygen uptake during a conventional treadmill test and the shuttle walking test in chronic airflow limitation.

The purpose of this study was to investigate the relationship between performance on the shuttle walking test and maximal oxygen uptake (VO2max) during a conventional treadmill test in patients with chronic airflow limitation. Two different techniques were used to measure oxygen consumption, i.e. conventional Douglas bag techniques (treadmill test) and a portable oxygen consumption meter (shuttle test). Initially, 19 patients performed a shuttle walking test (after one practice walk) and a maximal treadmill walking test, in a randomized, balanced design. Subsequently, 10 patients, (after one practice) completed an unencumbered shuttle walking test and one supporting the portable oxygen consumption meter, in random order. The results of the first experiment revealed a strong relationship between performance during the shuttle walking test and VO2max during the treadmill walking test (r = 0.88). The results of the second experiment consistently demonstrated an incremental increase in oxygen consumption and ventilation in response to the increasing intensity of the shuttle walking test. Again, a strong relationship between VO2max and performance on the shuttle test was demonstrated (r = 0.81). We concluded that the shuttle walking test is a valid field exercise test of functional capacity. Performance on the test relates strongly to VO2max, the traditional indicator of cardiorespiratory capacity.

Measurement of inspiratory muscle performance with incremental threshold loading: a comparison of two techniques.

BACKGROUND: Incremental threshold loading (ITL) is a test of inspiratory muscle performance which is usually performed by breathing through a weighted inspiratory plunger, the load on the inspiratory muscles being increased by externally adding weights to the intake valve. This is not a true threshold device and may be inaccurate. This method was compared with a true threshold device consisting of a solenoid valve which only opens to supply air at a predetermined negative mouth pressure. METHODS: Six naive, normal subjects (three men and three women) aged 22-24 years underwent three tests using each system. The inspiratory loads were increased every minute by equivalent amounts, -10 cm H2O with the solenoid valve and by 50 g with the weighted plunger, until the subjects could not inspire or sustain inspiration for a full minute. Six experienced subjects (four men and two women) aged 23-41 years were subsequently randomised to perform ITL with the solenoid valve, twice with the breathing pattern fixed and twice free. RESULTS: The solenoid valve generated a more accurate mouth pressure response and was less variable at higher loads than the weighted plunger. The work performed (expressed as the pressure-time product) was less with the solenoid valve but was more reproducible. ITL with the solenoid valve was not influenced by controlling the breathing pattern of the subjects. CONCLUSIONS: The solenoid valve has several features that make it superior to the weighted plunger as a device for ITL. It generates a more accurate mouth pressure response which is less variable at higher loads. Increases in load are smoother and quicker to introduce. ITL with the solenoid valve is not influenced by varying breathing patterns and does not require any external regulation.

Sequential treatment with low dose almitrine bismesylate in hypoxaemic chronic obstructive airways disease.

Daily dose schedules of 100-200 mg of almitrine bismesylate improve arterial blood gases in patients with hypoxaemic chronic obstructive airways disease (COPD) but dose related side effects are evident. In the present study, daily doses approximately half of those previously used were employed in a randomised double blind manner in 85 patients (age 35-79 years) with hypoxaemic COPD. After a one month period to check stability of arterial blood gases, patients were allocated to almitrine (A) or placebo (P) using an unequal code (60% A, 40% P). Tablets, 50-100 mg daily were stopped for one month after 3, 6 and 9 months to counteract drug accumulation. 50 patients in group A and 35 in group P were comparable on entry; mean age 65 (SD = 8) yrs., Pao2 7.8 (0.7) kPa (58.3 (5.0) mmHg), PaCO2 5.8 (0.8) kPa (43.2 (6.0) mmHg), forced expiratory volume in one second--FEV1 0.89 (0.25) l and 6 minute walking distance 296 (97) metres. The improvement in baseline PaO2 values was the same 0.8-1.3 kPa (6-9.8 mmHg) as with previous higher dose therapy. Approximately one third of patients did not respond, defined as PaO2 elevation > 0.67 kPa (5 mmHg). The sequential dosing scheme stabilised blood levels of almitrine within the therapeutic range of 280-300 ng.ml-1. After withdrawal of therapy arterial blood gases and spirometry reverted to pre-treatment levels, suggesting no permanent reversal of pathophysiology. Dose related side effects of breathlessness, indigestion and peripheral neuropathy were not observed. Nerve conduction studies revealed no difference in peripheral nerve dysfunction in hypoxaemic COPD between active and placebo therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in atrial natriuretic peptide concentrations during intravenous saline infusion in hypoxic cor pulmonale.

BACKGROUND: The pathogenesis of oedema in hypoxic cor pulmonale is poorly understood. One possibility is a failure of atrial natriuretic peptide release, leading to salt and water retention. This hypothesis was tested by observing the response to an intravenous saline challenge in patients with and without cor pulmonale. METHODS: Plasma atrial natriuretic peptide concentrations were measured before and for three hours after an intravenous saline load (0.1 ml 2.7% saline/kg/min for 60 minutes) in 20 patients with chronic obstructive airways disease. Ten patients with cor pulmonale, as judged clinically by the presence of peripheral oedema with a previously documented increase in the jugular venous pressure or pleural effusions during an acute exacerbation of airway obstruction (mean (SE) age 67 (3) years, FEV1 0.73 (0.08) 1, arterial oxygen tension (PaO2) 6.4 (0.4) kPa, and arterial carbon dioxide tension (PaCO2) 6.7 (0.3) kPa), were compared with 10 patients with hypoxic chronic obstructive airways disease who had never had oedema (mean age 63 (1) years, FEV1 1.07 (0.09) 1, PaO2 8.6 (0.4) kPa, and PaCO2 5.3 (0.2) kPa). All patients were studied fasting and after diuretics had been stopped for three days. No supplemental oxygen was given. RESULTS: The mean four hourly urine sodium excretion was less in the patients who had oedema (27 (4.6) mmol, 13% of the intravenous load) than in those without oedema (82 (15.5) mmol, 43% of the load). Initial mean plasma atrial natriuretic peptide values were significantly higher in the patients with cor pulmonale (19.1 (1.6) compared with 10.2 (0.7) pmol/l) and the mean peak rise in atrial natriuretic peptide after the intravenous saline load had been given was 13 (8.0) pmol/l in the patients with cor pulmonale and 5.5 (2.3) pmol/l in the controls. There were no significant differences in plasma and urinary osmolality, blood pressure, or creatinine clearance between the groups. CONCLUSION: Patients with chronic obstructive airways disease and cor pulmonale have an impaired ability to excrete a hypertonic intravenous saline load despite a normal physiological release of plasma atrial natriuretic peptide.

Oral almitrine in treatment of acute respiratory failure and cor pulmonale in patients with an exacerbation of chronic obstructive airways disease.

The effects of oral almitrine bismesylate, a respiratory stimulant that acts on peripheral arterial chemoreceptors, was studied in patients with chronic obstructive airways disease and hypoxaemic cor pulmonale. Twenty three patients admitted to hospital with an acute exacerbation of ventilatory failure were randomised to receive either almitrine 100 mg twice a day reducing to 50 mg twice a day over 48 hours or placebo in addition to conventional treatment. On admission the mean (SE) values for blood gas tensions were PaO2 4.8 (0.3) and PaCO2 7.7 (0.3) kPa in the 12 patients who received almitrine and PaO2 4.9 (0.1) and PaCO2 7.6 (0.3) kPa in the 11 who received placebo. After three hours of oxygen therapy at 1 1/min there was a similar rise in PaO2 in both groups, 6.4 (0.2) kPa in those receiving almitrine and 6.6 (0.4) kPa in those receiving placebo. After 24 hours of oxygen therapy values of PaO2 were again similar at 6.3 (0.8) kPa and 6.7 (2.2) kPa respectively. Arterial blood gas tensions improved during the study in those who survived but no significant differences were apparent between the two groups. There were six deaths, five in the almitrine group and one in the placebo group. There were no differences between the groups in respiratory rate, results of spirometry, oxygen requirement, or degree of dyspnoea (on visual analogue scale). The results did not show any benefit from oral almitrine in patients with acute respiratory failure secondary to chronic obstructive airways disease. Plasma almitrine concentrations, however, were often below the optimum therapeutic range, suggesting impaired drug absorption.

Two years treatment with almitrine bismesylate in patients with hypoxic chronic obstructive airways disease.

Eighty nine patients with hypoxic chronic obstructive airways disease (COAD) were enrolled into the 1 year Vectarion International Multicentre Study-VIMS in 4 centres, Sheffield (UK), and Antwerp, Liege and Namur (Belgium). At the end of the year the remainder were invited to continue taking placebo or almitrine bismesylate (100-200 mg daily) in the same double blind manner for a further 12 months. In the almitrine treated patients mean arterial oxygen tension (Pao2) at the end of the treatment period improved from 7.5 (0.5) kPa to 8.2 (1.3) kPa (p less than 0.01) and arterial carbon dioxide tension (Paco2) fell from 6.1 (0.8) kPa to 5.8 (0.9) kPa (p less than 0.01). Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and measurements of breathlessness were unchanged. In the placebo treated group changes in the above variables were not significant. Twenty nine patients withdrew from the almitrine group with seven deaths and six cases of peripheral neuropathy, and 22 patients withdrew from the placebo group with six deaths and two cases of peripheral neuropathy. Death rates between the groups were not significantly different. In conclusion, 2 yrs of almitrine treatment (100-200 mg daily) leads to a persistent slight improvement in PaO2 and PaCO2 but no benefit in survival was demonstrated. Patients in this study had a high incidence of drug related side-effects. Lower dose schedules should be investigated.

Natriuresis secondary to carotid chemoreceptor stimulation with almitrine bismesylate in the rat: the effect on kidney function and the response to renal denervation and deficiency of antidiuretic hormone.

Almitrine bismesylate simulates the effects of arterial hypoxia in producing a specific and long-lasting excitation of the peripheral arterial chemoreceptors. Previous work has shown that almitrine produces a diuresis and natriuresis when given intravenously to anaesthetised rats in a stable mannitol induced diuresis. This response is abolished by glossopharyngeal nerve section implying that it is afferently mediated via the carotid body chemoreceptors. We have studied further the efferent limb of this response. The diuresis and natriuresis occurs without significant detectable changes in effective renal plasma flow and glomerular filtration rate suggesting that it is produced mainly by inhibition of renal tubular sodium and water reabsorption. Almitrine produces a diuresis and natriuresis in rats after bilateral nephrectomy and transplantation of a kidney from a donor rat. This effect is not therefore efferently mediated by the renal nerves and probably involves a humoral agent. Almitrine produces a diuresis and natriuresis in rats after bilateral adrenalectomy and in rats with congenital hypothalamic diabetes insipidus indicating that neither adrenal hormones nor changes in antidiuretic hormone levels are implicated.

Pleural effusions and pancreatico-pleural fistulae associated with asymptomatic pancreatic disease.

Four patients are described in whom recurrent large pleural effusions developed secondary to asymptomatic pancreatic disease. The diagnosis was made by measuring the amylase content of the pleural fluid. Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) were useful in demonstrating pancreatico-pleural fistulae. Two patients underwent laparotomy and distal pancreatectomy. One recovered spontaneously after ERCP appeared to relieve an obstruction of the pancreatic duct and the other recovered after a period of parenteral nutrition. We suggest that pleural fluid amylase content should be measured in any case of exudative pleural effusion of unknown aetiology.

The carotid body and natriuresis: effect of almitrine bismesylate.

Almitrine bismesylate is a peripheral chemoreceptor agonist. When given intravenously to anaesthetized rats it results in a reversible diuresis and natriuresis. The effect is abolished by denervation of the carotid bodies and is still present following vagotomy, when the animal is paralysed and artificially ventilated or following bilateral adrenalectomy. Denervation of the carotid bodies results in a lower resting sodium excretion. In chronically hypoxic rats which have enlarged carotid bodies the natriuretic response to almitrine is grossly diminished.