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Biomedical subjects

A J Suggett

Publications and source records attributed to A J Suggett.

At least 19 recordsLinked to original sources
PubMed1990

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. Nine patients were withdrawn from the study (5 almitrine, 4 placebo). Patients' tolerance of the drug was good. The estimated plasma half life of almitrine was 20.5 days, considerably longer than previously reported. Almitrine caused a significant improvement in arterial oxygen tension (PaO2) with a mean maximum increase of 0.7 kPa at a plasma concentration of 500 ng/ml. Higher plasma concentrations were not associated with any further increase in PaO2. There was no significant effect on arterial carbon dioxide tension (PaCO2). In a second, acute study at the end of each arm of the chronic trial nine patients were subjected to increasing oxygen delivery rates (2, 4, and 6 l/min) for 90 minutes or until blood gas concentrations plateaued. Almitrine increased PaO2 in a dose dependent fashion at all delivery rates, but the effect diminished as PaO2 approached normoxic levels. There was no significant effect on PaCO2. Almitrine treatment results in a significant improvement in PaO2 over that achieved by oxygen alone, an effect that diminishes at high flow rates. Whether this is of clinical benefit is not known. In view of the prolonged half life revised dosage schedules are required.

Almitrine↗
PubMed1988

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 9.5 (PGP 9.5), a general marker of nerves and endocrine cells, were quantified in sections of lungs from hypoxic (21 days, 10 per cent O2) and normoxic rats. An immunostaining method employing supra-optimal dilutions of primary antiserum was used. This detects variations in antigen concentration which may be masked if the routine, optimal dilution is used. The number of CGRP-immunoreactive endocrine cells was significantly (P less than 0.001) greater in the lungs of hypoxic rats (76.9 +/- 10.1 cells/cm2, mean +/- SEM) compared with controls (19.7 +/- 2.4). However, the numbers of PGP 9.5-immunoreactive cells were the same in both groups (81.3 +/- 12.2, hypoxic; 79.5 +/- 9.8 control), suggesting that the total number of endocrine cells did not change. It is concluded therefore that the apparent increase in CGRP-immunoreactive endocrine cells in hypoxic rat lungs is due to increased intracellular levels of the peptide. Since CGRP is a vasodilator, this could have important implications in the vasoconstrictor response to hypoxia.

APUD Cells↗
PubMed1988

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. Conventional therapies were continued unchanged. The effects of the drug on pulmonary haemodynamics were inconclusive when considered overall, but total pulmonary vascular resistance (TPVR) fell in all patients on active therapy in whom measurements were obtained both at rest and upon exercise. Only one patient in the placebo group achieved this. Over the trial period there was one death in the active but five in the placebo group. Survival was unrelated to abnormalities in pulmonary haemodynamics at the commencement of the trial in this study although the numbers of patients was small. Postural hypotension developed in patients receiving methyldopa and limited the dose that could be administered. The problems involved in long term trials of vasodilators in hypoxic cor pulmonale are discussed.

Aged↗
PubMed1988

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. Calibration of the system allows continuous monitoring of the level of ventilation on exercise up to a minute volume of 45 l min-1. The volumetric accuracy of the system is generally within +/- 10% of spirometric measurements. Studies of the effect of changes in posture on the calibration of the system show changes of between +9.5% and -3.8% in normal male subjects. The performance of the system compares favourably with existing techniques for the noninvasive monitoring of ventilation.

Humans↗
PubMed1988

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.

Electrodes↗
PubMed1988

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.

Animals↗
PubMed1988

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 this device on arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions was assessed over 60 min in twelve patients with severe hypoxaemia (6.2 +/- 0.9 kPa, mean +/- SD) and hypercapnia (7.5 +/- 1.2 kPa). Following baseline measurements, oxygen was administered using standard nasal cannulae, and further measurements were made at 15 min intervals for at least 45 min. Patients were then changed to the "Oxymizer" and measurements continued at 15 min intervals for a further 60 min. Mean PaO2 increased by 1.1 +/- 0.78 kPa (p less than 0.001), using the "Oxymizer", but PaO2 was significantly greater after 15 min on the device than after 60 min (p less than 0.05). There was no change in PaCO2 (p greater than 0.05). The "Oxymizer" increases PaO2 compared with standard cannulae, but the effect may not be sustained.

Aged↗
PubMed1987

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. To assess the performance and possible clinical applications of APT, measurements have been made following increases in lung volume and pulmonary blood volume. During inspiration an increase in both the area and the magnitude of the impedance changes over the area of the lungs was observed. Numerical analysis of the impedance changes in normal subjects reveals a consistently high correlation between the volume of air inspired and the magnitude of the impedance changes. The resolution of the system is sufficient to monitor differences in ventilation in the right and left lung and to measure variations in these levels with posture. Preliminary clinical work suggests that APT may be used to detect ventilatory defects in certain types of lung disease. APT measurements show a decrease in resistivity over the area of the lungs when the pulmonary blood volume is increased by the intravenous infusion of 1.5 litres of isotonic saline. Similar changes in the volume of fluid in the lungs are known to occur in pulmonary oedema. APT measurements of lung impedance may detect the onset of pulmonary oedema in high risk patients.

Adult↗
PubMed1987

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.

Adrenal Glands↗
PubMed1986

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 (0.5 mg/kg + 10 micrograms/kg per min, i.v.) caused a rise in pulmonary artery pressure (PPA), increased flow through the hypoventilated lobe in six out of seven cats and both increased or decreased lobar vascular resistance (PVR); the lobar V/Q ratio therefore fell. Arterial and lobar venous oxygen tension (PO2) fell. In five dogs almitrine caused a rise in PPA and PVR but lobar flow changes were variable. Arterial and lobar venous PO2 fell. With fixed ventilation, almitrine failed to improve V/Q matching; there was no improvement in gas exchange in the hypoventilated lobe. In eight dogs the hypoventilated lobe was perfused at constant flow with right atrial blood (i.e. while V/Q was held constant). Almitrine caused a rise in perfusion pressure, vasoconstriction, followed, in five out of eight dogs, by vasodilatation. In six similar cat preparations, vasoconstriction but not vasodilatation was clearly shown. In two cats dilatation after almitrine was demonstrated during ventilation with Nitrogen. In all experiments there was no significant effect of the solvent. Thus the dual action of almitrine seen in other species was seen in a proportion of cats and dogs. Results do not support the view that improved arterial gas tensions in patients after almitrine are attributable to diversion of blood flow away from hypoxic lung. Alternative mechanisms are discussed.

Almitrine↗
PubMed1986

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 0.5 mm), measured from X-rays, was less in chronically hypoxic than normoxic rats when filled at the same perfusion pressure. Diameters increased in both groups with increasing perfusion pressure but at a given pressure those of chronically hypoxic rats were always smaller than those of normoxic rats. We found evidence that arterial length was increased in chronically hypoxic rats. Arterioles of 50 micron or less in diameter adjacent to gas exchange units were of similar external diameter in normoxic and chronically hypoxic rats, but most of the latter had developed a muscular coat and a second elastic lamina internal to the single elastic lamina of control arterioles. These changes reduced the lumen by an estimated 10-14% and would increase pulmonary arteriolar resistance in chronically hypoxic rats, resulting in a changed pressure profile. We found no evidence of arteriolar loss in chronically hypoxic rats although at a given pressure, the Ba-gelatine mixture penetrated less far for reasons which are discussed.

Angiography↗
PubMed1985

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. This procedure increased hematocrit (60 +/- 3%) but also increased blood volume (P less than 0.05). Following transfusion, resting cardiac output (QT) and heart rate were not different. During exercise, QT was significantly lower at each level of O2 consumption (VO2) at high hematocrit (P less than 0.01). A reduction in QT was also seen during polycythemic exercise with hypoxemia produced by breathing 12 or 10% O2 in N2. Despite the reduction in QT, mixed venous PO2 was not lower at high hematocrit, and the increase in base deficit with VO2 was not different from control measurements. O2 delivery (QT X arterial content) was similar at each level of VO2 at both levels of hematocrit, during both normoxic and hypoxic studies. Both systemic and pulmonary arterial pressures were increased at rest after transfusion (P less than 0.05). However, pulmonary and systemic pressures were not higher than control during exercise at high hematocrit. We conclude that a hematocrit of 60% with increased blood volume is not associated with a cardiac limitation of O2 delivery, nor does it interfere with peripheral O2 extraction during exercise in the dog.

Animals↗
PubMed1985

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 +/- 1.8 Torr) and again after P50 was lowered (19.5 +/- 0.7 Torr) by sodium cyanate infusions. Measurements were made during ventilation with room air (RA), 12% O2 in N2, or 10% O2 in N2. Cardiac output (QT) as a function of O2 consumption (VO2) was not altered by low P50 at any inspired O2 fraction (P greater than 0.05). With RA exercise, arterial content (CaO2) and O2 delivery (QT X CaO2) were unchanged at low P50, whereas mixed venous PO2 was reduced at each level of VO2. With exercise in hypoxia, CaO2 and O2 delivery were significantly improved at low P50 (P less than 0.05). Mixed venous PO2 was lower than control during 12% O2 (P less than 0.05) but not different from control during 10% O2 exercise at low P50. Despite a presumed decrease in tissue PO2 during RA and 12% O2 exercise, exercise performance and base excess decline were not significantly worse than control levels. We conclude that, in canine steady-state exercise, hemoglobin P50 is not an important determinant of tissue O2-extraction capacity during normoxia or moderate hypoxia. In extreme hypoxia, low P50 may help to maintain tissue PO2 by enhancing systemic O2 delivery at each level of QT.

Animals↗
PubMed1983

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). In vivo and isolated preparations were used. In all preparations and species almitrine bismesylate caused vasoconstriction in normoxia, constriction followed by dilation in hypoxia or hypoventilation. In hypoventilated lung there is ventilation/perfusion mismatching which was not improved by almitrine bismesylate . Ventilatory measurements in chronically hypoxic/hypercapnic rats showed that almitrine bismesylate increased tidal volume but not frequency. It is uncertain whether vascular (Q) or small ventilatory (V) changes are the cause of the improved gas tensions and V/Q matching in patients with chronic obstructive lung disease receiving almitrine bismesylate .

Almitrine↗
PubMed1982

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.

Adenosine Diphosphate↗
PubMed1982

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. 2. VLDL were incubated with bovine milk lipoprotein lipase (LPL) and a 9,10-3H-labelled triglyceride emulsion. The VLDL deficient in apolipoprotein C-II were a poor activator of LPL, compared with the effect of VLDL with normal content of apolipoprotein C-II obtained from either normal or hypertriglyceridaemic sera. 3. The efficacies of various VLDL as substrates fo activated LPL were examined. Apolipoprotein C-II-deficient VLDL were a poor substrate for the activated enzyme compared with normal or hypertriglyceridaemic VLDL, and compared wtih an artificial triglyceride emulsion. 4. The abnormal VLDL were obtained from a subject with an IgG3 lambda myeloma protein. Intravenous infusion of normal plasma containing apolipoprotein C-II was followed by rapid, complete, but short-lived (5-10 days) clearance of serum triglyceride. The effect was observed on three occasions until treatment of the myeloma was effective. 5. The monoclonal protein behaved as a cryoglobulin, and formed large particle complexes with triglyceride-rich lipoproteins, especially at temperatures below 37 degrees C. The apolipoprotein C-II deficiency, and consequent hypertriglyceridaemia, may be secondary to an autoantibody directed against apolipoprotein C-II. VLDL from relatives with hypertriglyceridaemia, but without myeloma, had normal apolipoprotein content, activated LPL, and were efficient substrates for the enzyme.

Adult↗