Almitrine bismesylate and oxygen therapy in hypoxic cor pulmonale.

The effect of oral treatment with the thiazine derivative almitrine bismesylate was studied in 28 patients with chronic obstructive pulmonary disease and arterial hypoxaemia receiving long term domiciliary oxygen therapy in a placebo controlled, double blind crossover trial. The initial treatment was given for three months and the second for two months. Because almitrine had an unexpectedly prolonged washout effect crossover analysis could not be performed; data from the placebo treatment administered in the second arm of the trial were used to calculate the half life of almitrine.

A conservation device for oxygen therapy in COPD.

Patients with hypoxaemia secondary to chronic obstructive pulmonary disease (COPD) are frequently prescribed oxygen therapy for short- and long-term domiciliary use. Oxygen administered via nasal cannulae incorporating a small collapsible reservoir ("Oxymizer", Chad Therapeutics Inc., CA, USA) improves transcutaneous oxygen tensions in the short-term when compared to standard nasal cannulae.

The effects of long term methyldopa in patients with hypoxic cor pulmonale.

Methyldopa (alpha-methyldopa) was given to patients with cor pulmonale secondary to chronic obstructive airways disease (COAD) to determine its effect on pulmonary haemodynamics. Twenty-five patients were randomly allocated to methyldopa (750 mg daily) or placebo. Pulmonary haemodynamics were measured twice, 12 months apart.

Experimental prevention of hypoxic pulmonary hypertension in animals by drugs.

The rat model of chronic hypoxic pulmonary hypertension has been extensively studied and shows many of the features seen in man with chronic pulmonary hypertension. The development and reversibility of these changes by various treatments and by drugs is discussed. The experimental model may provide valuable clues as to the mechanisms involved in the aetiology of pulmonary hypertension in man.

Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells of hypoxic rats.

The mammalian respiratory tract contains innervated groups of endocrine cells which are believed to respond to hypoxia. We have demonstrated the involvement of a specific regulatory peptide produced by the cells, calcitonin gene-related peptide (CGRP), in this response. Cells immunoreactive for CGRP or for protein gene product 9.

An assessment of dynamic images by applied potential tomography for monitoring pulmonary perfusion.

Applied potential tomography (APT) images can be collected at a rate of 24 per second and data collection can be synchronised with the ECG. Images thus obtained from a thoracic plane allow the spatial separation of impedance changes originating in the heart, aorta and lungs and have raised the possibility of detecting pulmonary perfusion abnormalities from the cardiac-related impedance changes in the lungs. We have recently started a study to compare isotope perfusion scans with APT images and present here a few initial examples which suggest that further investigation of this field may prove rewarding.

Applied potential tomography: a new technique for monitoring pulmonary function.

An electrical impedance tomographic imaging system has been developed which can monitor changes in the resistivity of the thorax at a rate of 5 frames per second. There is a high correlation (r greater than 0.95) between changes in resistivity of the lungs and the volume of air inspired.

Effect of almitrine bismesylate on breathing pattern during hypoxia/hypercapnia in rats and ferrets.

1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to breath appropriate gas mixtures or by increasing the tracheal resistance or dead-space.

Applications of applied potential tomography (APT) in respiratory medicine.

Impedance pneumography, electrical impedance measurements of the lung, is a technique which has been widely used to monitor respiration non-invasively and more recently, the onset of pulmonary oedema. Attempts have been made to try to localise the changes in impedance using electrode arrays and electrode guarding. These techniques allow localisation to a particular hemithorax, but the resolution of the majority of the systems remains poor.

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.

Action of almitrine bismesylate on ventilation-perfusion matching in cats and dogs with part of the lung hypoventilated.

Ventilation to one lobe of lung was reduced in anaesthetized open-chest cats and dogs to simulate the ventilation/perfusion (V/Q) mismatching of chronic lung disease. Blood flow to this lobe fell less than ventilation; thus lobar V/Q diminished. In seven cats almitrine (0.

Quantitative changes in the rat pulmonary vasculature in chronic hypoxia--relation to haemodynamic changes.

The anatomical basis of resistance and compliance changes of the pulmonary arterial bed was studied in rats exposed to chronic hypoxia (10% O2, 3 weeks) and the findings were compared with those of normoxic rats. The lungs were perfused with a Ba-gelatine mixture at different pressures and studied by radiology and histology. The diameter of the pulmonary arteries (greater than 0.

Role of hemoglobin P50 in O2 transport during normoxic and hypoxic exercise in the dog.

High hemoglobin affinity for O2 [low PO2 at 50% saturation of hemoglobin (P50)] could degrade exercise performance in normoxia by lowering mean tissue PO2 but could enhance O2 transport in hypoxic exercise by increasing arterial O2 saturation. We measured O2 transport at rest and at graded levels of steady-state exercise in tracheostomized dogs with normal P50 (28.8 +/- 1.

Effects of transfusion-induced polycythemia on O2 transport during exercise in the dog.

An increased hematocrit could enhance peripheral O2 transport during exercise by improving arterial O2 content. Conversely, it could reduce maximal delivery of O2 by limiting cardiac output during exercise or by limiting the distribution of blood flow to peripheral capillaries with high O2 extractions. We studied O2 transport at rest and during graded treadmill exercise in splenectomized tracheostomized dogs at normal hematocrit (38 +/- 3%), and 48 h after transfusion of type-matched donor cells.

Does almitrine bismesylate improve V/Q matching? An animal study.

Pulmonary vascular actions of almitrine bismesylate were studied in ferrets, rats, cats and dogs in conditions which simulated those of patients with hypoxic lung disease. All or part of a lung was made hypoxic or hypoventilated so that affected vessels were constricted. Rats were made chronically hypoxic (10%, O2, normobaric chamber).

The effects of localized hypoventilation on ventilation/perfusion (V/Q) ratios and gas exchange in the dog lung.

1. Hypoventilation of one lobe of lung was studied in open-chest anaesthetized dogs. Lobar blood flow, pulmonary-artery pressure and gas exchange were measured, the latter from breath-by-breath analysis with a mass spectrometer.

Effect of alpha-methyldopa on lung microembolism in the rat.

The effect of chronic pretreatment with alpha-methyldopa on acute pulmonary hypertension induced by lung microembolization with Sephadex particles in the rat was studied. Alpha-methyldopa was administered twice a day for 10 days by oesophageal gavage (20 mg X kg-1 of body weight) prior to embolization. Rats were anaesthetized with urethane.

Effect of acetylsalicylic acid on platelet aggregation and thromboxane B2 production in flowing aortic blood in the rat studied with a filter loop technique.

A method of measuring in vivo platelet function using a filter loop technique has been used to study platelet aggregation in response to Adenosine Diphosphate (ADP) and Sodium Arachidonate infusion in flowing aortic blood in the rat. ADP infusion produced reversible platelet aggregation in vivo with no change in thromboxane B2 (TXB2) levels whereas sodium arachidonate infusion resulted in virtually irreversible aggregation with a rise in TXB2 levels. Oral Acetylsalicylic Acid (ASA) in doses of 1-100 mg/kg had no effect on ADP induced aggregation but prevented platelet aggregation in vivo induced by sodium arachidonate and the concomitant rise in TXB2 levels.

Studies of a variant very-low-density lipoprotein with an acquired deficiency of apolipoprotein C-II.

1. A variant very-low-density lipoprotein was associated with severe hypertriglyceridaemia. Urea-polyacrylamide gel electrophoresis of the tetramethylurea-soluble apolipoproteins of these very-low-density lipoproteins (VLDL) showed that the apolipoprotein C-II content was less than 10% of that in VLDL from hypertriglyceridaemic (3-120 mmol/l) controls.

Quantitative significance of hypoxic vasoconstriction in the ferret lung.

Stimulus-response curves for the pulmonary vascular bed to alveolar hypoxia have been measured in ferrets under conditions of perfusion either at constant pressure or a constant flow in vivo or in isolated lungs. In all circumstances the relationship between alveolar oxygen tension and the fall in blood flow or rise in pulmonary artery pressure was sigmoid although there were important differences between the in vivo and in vitro preparations. The significance of these observations in constant pressure and constant flow preparations in relation to pulmonary hypertension and ventilation/perfusion regulation is discussed.

Electron microscopy of network structures in thermally-induced globular protein gels.

Thin sections of heat-set proteins gels formed from bovine serum albumin, insulin, lysozyme, ribonuclease, and alpha-chymotrypsin, have been studied by transmission electron microscopy. Micrographs have been interpreted as showing protein networks with strands between one and two times as thick as the native protein diameters. Considerable differences in the persistence characteristics, and frequencies of cross-linking, of the strands are observed, and there are variations in network homogeneity over long distances which correlate well with changes in gel opacity caused by alterations in pH and ionic strength.

Infrared and laser-Raman spectroscopic studies of thermally-induced globular protein gels.

Infrared and laser-Raman spectroscopy have been used to follow secondary structure changes during the heat-set gelation of a number of aqueous (D2O) globular protein solutions. Measurements of the infrared Amide I' absorption band around 1650 cm-1, for BSA gels of varying clarity and texture, have shown that the very considerable variations in network structure underlying these materials are not reflected in obvious differences in secondary structure. In all cases aggregation is accompanied by development of beta-sheet of a kind common in fibrous protein systems, but for BSA at least this does not appear to vary significantly in amount from one gel type to another.