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Biomedical subjects

D C Flenley

Publications and source records attributed to D C Flenley.

At least 37 records · Page 2Linked to original sources

The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale.

We made simultaneous measurements of pulmonary hemodynamics, cardiac output, and right ventricular ejection fraction (RVEF) to assess the right ventricular function in 14 patients with pulmonary arterial hypertension as a result of chronic obstructive pulmonary disease (COPD). From these measurements, the right ventricular end-systolic pressure/volume relationship could be calculated and used to assess right ventricular contractility. Eight of the patients were clinically stable, without edema, and 6 presented acutely with gross edema, indicating decompensated cor pulmonale. Measurements were made at rest, while breathing air and oxygen. Although mean pulmonary arterial pressure (Ppa) was similar in those with (Ppa = 33 +/- 6 mm Hg) and without edema (Ppa = 30 +/- 8 mm Hg, p greater than 0.05), RVEF was lower in edematous (RVEF = 0.23 +/- 0.11) compared with non-edematous patients (RVEF = 0.47 +/- 0.04, p less than 0.01). Cardiac output was normal in both groups. The mean right ventricular end-systolic pressure/volume ratio (P/V) was lower in those patients with edema (P/V = 0.41 +/- 0.27), as compared with those without edema (P/V = 1.69 +/- 0.35, p less than 0.05), as a result of an increase in right ventricular end-systolic volume index. Similarly, left ventricular end-systolic volumes were higher in edematous than in non-edematous patients. Breathing 1 to 3 L/min of oxygen for 30 min decreased total pulmonary vascular resistance (p less than 0.05) in those patients without edema, but not in patients with edema. Oxygen did not change RVEF, left ventricular ejection fraction (LVEF), or the ventricular end-systolic P/V relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Pulmonary hypertension and right ventricular function in patients with COPD.

In 100 patients with chronic obstructive pulmonary disease (COPD), we found no significant correlation between simultaneous measurements of right ventricular ejection fraction, using radionuclide ventriculography, and pulmonary arterial pressure. There was, however, a weak but significant correlation between right ventricular ejection fraction and the pulmonary vascular resistance (r = 0.40, p less than 0.005). In 52 of these patients, 37 with pulmonary hypertension, right ventricular end-systolic volume index was 53 +/- 21 ml.m-2 and end-diastolic volume index was 86 +/- 27 ml.m-2, compared with a calculated mean of 33 ml.m-2 and 79 ml.m-2, respectively, for normal subjects. In 24 of these patients where the measurements were made at rest and on exercise, the mean right ventricular end-systolic volume increased from 66 +/- 20 ml.m-2 to 87 +/- 32 ml.m-2, with an increase in right ventricular systolic pressure from 28 +/- 9 mm Hg to 55 +/- 15 mm Hg. Analysis of the slope of the right ventricular end-systolic pressure volume relationship at rest and on exercise suggested relatively normal right ventricular contractility in the majority of patients. Thus, in these patients with stable COPD, despite the presence of pulmonary hypertension, right ventricular contractility remained relatively normal.

Blood Pressure↗

Effect of sustained release terbutaline on symptoms and sleep quality in patients with nocturnal asthma.

The effect of an oral sustained release beta 2 agonist on symptoms, sleep quality, and peak flow rates has been studied in nine patients with nocturnal asthma. Patients received oral terbutaline 7.5 mg twice daily or placebo for seven days in a double blind crossover study and spent the last two nights of each limb in a sleep laboratory. Oral terbutaline improved morning peak flow (259 v 213 l min-1) and decreased nocturnal inhaler usage (1.3 v 1.9) with no alteration in sleep quality as assessed electroencephalographically. The study shows that oral sustained release terbutaline can be useful in the treatment of nocturnal asthma without impairment of sleep quality.

Administration, Oral↗

Sodium cromoglycate in nocturnal asthma.

To investigate whether mast cell degranulation was important in producing nocturnal asthma, the effect of a single high dose of nebulised sodium cromoglycate on overnight bronchoconstriction, oxygen saturation, and breathing patterns in eight patients with nocturnal wheeze was examined. The study took the form of a double blind placebo controlled crossover comparison. Treatment with cromoglycate did not reduce the overnight fall in FEV1 or FVC, although it was associated with improved nocturnal oxygenation. This study suggests that mast cell degranulation may not be important in the pathogenesis of nocturnal asthma.

Adolescent↗

Reversible airway obstruction: neurohumoral mechanisms and treatment. Lecture on asthma: clinical overview.

Asthma is an airway obstruction which is reversible, either spontaneously or in response to treatment. Repeated peak expiratory flow rate (PEFR) measurements, up to six times daily, allows this characteristic reversibility to be recognised, to guide diagnosis and therapy. Chronic asthmatics may eventually become relatively irreversible, and then appear similar to chronic bronchitics - unless an adequate history is taken. The commonest world-wide allergen is the fecal pellet of the house mite. Modern therapy of asthma starts with inhaled beta 2 agonists, but difficulty in using metered dose inhalers is helped by the 'spacer', or reservoirs (e.g. 'Nebuhaler'). Interaction between slow-release oral theophyllines and beta 2 agonists by inhalation maximises bronchodilatation but minimises tremor. High-dose ipratropium inhalation, as isotonic wet nebulisation with a beta 2 agonist, is useful in acute severe asthma. High doses of inhaled topical steroid are valuable in the difficult asthmatic, but pituitary adrenal suppression occurs if dosage exceeds 1,500 micrograms/day. Cromoglycate and a beta 2 agonist by inhalation can prevent exercise-induced asthma. Long-term oral steroids (never over 10 mg/day) are only used if inhaled therapy (+/- oral slow-release theophyllines) fails. Acute severe asthma needs parenteral steroid, parenteral beta 2 agonist, high-dose beta 2 agonist by inhalation, oxygen and hospital admission. Ventilation is increased in the acute severe asthmatic with hypoxia and low PCO2. In 90 asthmatic deaths surveyed in Britain, half had failed to realise the severity.

Administration, Topical↗

Reversible airway obstruction: neurohumoral mechanisms and treatment. Lecture on nocturnal asthma.

Nocturnal wheeze has been known for at least 300 years, but only recently widely recognised. Wakening between 3 and 4 a.m. with wheeze may be associated with a 'morning dip' in peak expiratory flow rate (PEFR), worse in REM sleep, and with a circadian rhythm. Earlier suggestions that plasma histamine rose with nocturnal bronchoconstriction cannot be confirmed, but circulating adrenaline may be reduced in asthmatics at night. Hypoxia at night is common in asthmatics, associated with hypoventilation in REM sleep. Increasing frequency of nocturnal wheeze may herald acute severe asthma. Beta 2 agonists inhaled on retiral do not last to prevent the 'morning dip' in PEFR, but slow-release theophyllines can prevent this, and also relieve symptoms. However, sleep is still disturbed (by EEG criteria), as is nocturnal hypoxaemia. Nocturnal wheeze and/or 'morning dip' in PEFR occur in both atopic and non-atopic asthmatics, and the mechanism of nocturnal wheeze remains to be determined. Recognition of this common symptom remains a major indication for oral slow-release theophyllines.

Airway Obstruction↗

A comparison of the effects of almitrine or oxygen breathing on pulmonary arterial pressure and right ventricular ejection fraction in hypoxic chronic bronchitis and emphysema.

Almitrine bismesylate is a new, orally administered, respiratory stimulant that improves arterial blood gas tensions in patients with chronic bronchitis and emphysema, and it may have an effect on the pulmonary circulation and on right ventricular performance. We have, therefore, compared the effects of Almitrine with those of oxygen (given as 3 L/min by nasal prongs) on arterial blood gas tensions, mean pulmonary arterial pressure (Ppa), and right ventricular ejection fraction (RVEF) measured both at rest and during exercise in patients with chronic hypoxemia caused by chronic bronchitis and emphysema. Arterial oxygen tension improved significantly both at rest and during exercise after either 100 mg Almitrine by mouth or when breathing oxygen, both at rest and during exercise. Almitrine increased the mean Ppa at rest from 22 +/- 4 to 35 +/- 5 mmHg (p less than 0.001), and mean Ppa rose further during exercise from 38 +/- 5 mmHg before Almitrine to 49 +/- 7 mmHg (p less than 0.001) after Almitrine. In contrast, oxygen breathing did not change Ppa when at rest but reduced the amount of rise in Ppa during exercise. The change in Ppa after Almitrine correlated with the plasma Almitrine concentration (r = 0.69, p less than 0.05) and was associated with a fall in RVEF at rest from 0.38 +/- 0.03 to 0.32 +/- 0.02 (p less than 0.001). In 5 of the patients who received 50 mg of Almitrine by mouth twice daily for 3 months, the Ppa both at rest and during exercise remained significantly higher than in the control study before receiving Almitrine, but RVEF was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Disodium cromoglycate fails to prevent the rise in pulmonary artery pressure in hypoxic chronic bronchitis and emphysema.

Animal studies have suggested that stabilising mast cells may reduce the rise in pulmonary artery pressure which is produced by hypoxia. In six patients with stable hypoxic chronic bronchitis and emphysema, we have compared the pulmonary artery pressure at rest and on exercise before and after inhaling disodium cromoglycate (DSCG). The increase in heart rate was the same after each period of exercise (17 beats/min increase on placebo; 16 beats/min on DSCG), as was fall in arterial oxygen saturation (6% on placebo; 6% on DSCG). The subsequent rise in pulmonary artery pressure (PAP) during exercise was also not significantly different between placebo and DSCG. We conclude that 80 mg of aerosolised DSCG does not modify the pulmonary artery pressure in patients with chronic bronchitis and emphysema either at rest or during exercise.

Aged↗

Sustained release choline theophyllinate in nocturnal asthma.

Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.

Adult↗

Problems before, during and after mechanical ventilation in chronic bronchitis and emphysema.

Recent work has shown considerable advance in the potential for treatment of patients with acute exacerbations of chronic respiratory failure, and the "blue and bloated" pattern of chronic bronchitis and emphysema. New guidelines for controlled oxygen therapy have been developed, which appear to enable the dangers of hypoxaemia and respiratory acidosis in an acute exacerbation to be reduced. New modalities of therapy, long-term oxygen treatment. Almitrine, and beta 2-agonists, hold promise of prolonging the survival of useful life in these severely afflicted patients.

Acidosis, Respiratory↗