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Biomedical subjects

D L Maxwell

Publications and source records attributed to D L Maxwell.

At least 37 records · Page 2Linked to original sources
PubMed1988

The effect of almitrine bismesylate on the steady-state responses of arterial chemoreceptors to CO2 and O2 in the cat.

The interaction between almitrine bismesylate, a pharmacological stimulant of peripheral chemoreceptors, and varying levels of oxygen (PO2 50-600 Torr) and carbon dioxide (PCO2 10-65 Torr) on steady state carotid chemoreceptor discharge was investigated in pentobarbitone-anaesthetised cats. Almitrine was given as constant intravenous (50 micrograms/kg per min for 4 min) and intracarotid infusions (4-16 micrograms/kg per min) at different levels of alveolar PO2 and PCO2. Almitrine always excited discharge. The intracarotid infusions at the lower infusion rate (4-8 micrograms/kg per min) and the i.v. infusions increased the slope of the isoxic response to CO2. This effect could be reversed by raising PO2 to high levels. Higher infusion rates of almitrine (16 micrograms/kg per min) displaced the CO2 response curve upwards but did not increase its slope above that obtained in control conditions at end-tidal PO2 of 50 Torr. However, as these higher infusion rates caused levels of discharge greater than those achieved during control conditions, their effects on control CO2 sensitivity could not be ascertained. Our results suggest that almitrine excites carotid body chemoreceptors by a mechanism similar to that of hypoxia and not like that of carbon dioxide.

Almitrine↗
PubMed1987

Ventilatory effects of inhaled capsaicin in man.

Nebulised capsaicin (10(-7) M) was inhaled by 8 normal subjects to study its effects on the pattern of breathing. When compared to the diluent alone capsaicin increased mean inspiratory flow, a reflection of central inspiratory drive (mean increase: 25 +/- 6%, SEM, p less than 0.01), with a trend to increasing ventilation through more rapid but not more shallow breathing. If capsaicin selectively stimulates non-myelinated fibres in the lung in man as it does in dogs, these results suggest that such stimulation in man can alter the pattern of breathing.

Adult↗
PubMed1987

Autoregulation of retinal blood flow in diabetic retinopathy measured by the blue-light entoptic technique.

Autoregulation of retinal blood flow was measured in 23 diabetic patients, 9 with nonproliferative retinopathy, 9 with proliferative retinopathy, and 5 with photocoagulated retinopathy. Three of the proliferative patients were studied on two occasions, at the proliferative stage and after photocoagulation. The stimuli to autoregulation used were isocapnic hyperoxia and hypoxia. Flow velocity of leukocytes in the perifoveal circulation was measured using the blue-field entoptic technique, and retinal artery and vein diameters were measured using a computerized digitizing system. Results under conditions of isocapnic hypoxia showed a mean increase in flow velocity of 41.0 +/- 33.0% (P less than 0.05) in nonproliferative retinopathy, 3.5 +/- 17.0% (not significant) in proliferative retinopathy, and 30.0 +/- 17.0% (P less than 0.05) after photocoagulation. In hyperoxia, flow velocity fell by a mean of 21.0 +/- 21.6% (P less than 0.05) in nonproliferative retinopathy, 33.0 +/- 19.9% (P less than 0.005) in proliferative retinopathy, and 21.0 +/- 26.0% (not significant) in photocoagulated retinopathy. The results are compared with a group of nondiabetic subjects reported previously.

Adult↗
PubMed1987

Acute ventilatory changes during i.v. induction of anaesthesia with thiopentone or propofol in man. Studies using inductance plethysmography.

We have compared the acute ventilatory changes during induction of anaesthesia with equipotent doses of thiopentone and propofol in 12 premedicated female patients. Using ventilatory inductance plethysmography we have shown that both agents depress respiration to a similar and significant degree (P less than 0.001). However, although the functional residual capacity was reduced in patients receiving propofol, it increased slightly after induction with thiopentone (P less than 0.05).

Adult↗
PubMed1987

Circulatory and respiratory effects of infused adenosine in conscious man.

1. The nucleoside, adenosine, was infused into six conscious healthy male subjects at rates up to 100 micrograms kg-1 min-1. 2. Compared with a control 0.9% saline infusion, adenosine in all subjects caused dose dependent increases in heart rate, skin temperature and minute ventilation with corresponding falls in PaCO2, estimated transcutaneously. 3. There were no changes in systemic blood pressure, airways resistance (measured by forced partial expiratory manoeuvres), or plasma catecholamines. At the top infusion rates subjects experienced tolerable chest and abdominal discomfort. 4. These findings conflict with some previous studies in anaesthetised man and animals, in which higher doses of adenosine and its long acting analogues have caused hypotension and central respiratory depression. 5. Although some of these changes may have been due to symptoms, the cardiovascular changes may have been due to a vasodilator action and the respiratory stimulation may have been due to an action on peripheral chemoreceptors.

Adenosine↗
PubMed1987

Contrasting effects of two xanthines, theophylline and enprofylline, on the cardio-respiratory stimulation of infused adenosine in man.

Six normal male subjects, ages 28-40 years, were studied on separate days during increasing infusions with adenosine, 40-120 micrograms kg-1 min-1, before and during infusions of two xanthine derivatives, theophylline (mean plasma concentration 9 mg l-1) and enprofylline (mean plasma concentration 3 mg l-1). The study was double-blind, randomized, placebo controlled. Cardio-respiratory variables were measured non-invasively. Adenosine by itself increased heart rate (P less than 0.05), skin temperature (P less than 0.05), resting minute ventilation (P less than 0.01) and decreased estimated Pa, CO2 (P less than 0.01). Compared with placebo enprofylline increased heart rate (P less than 0.05) and shifted the heart rate and ventilation dose-response curves of adenosine upwards (P less than 0.05 and P less than 0.02, respectively). Theophylline did not by itself affect heart rate but significantly (P less than 0.05) reduced the heart rate response to adenosine. Compared with placebo theophylline caused a small increase in minute ventilation (P less than 0.05) and flattened the dose-response curves of the effects of adenosine on ventilation (P less than 0.01) and Pa, CO2 (P less than 0.01). Theophylline also reduced abdominal and chest discomfort caused by adenosine permitting significantly (P less than 0.05) higher infusion rates of adenosine. These findings suggest that, with equipotent bronchodilating plasma concentrations, theophylline can inhibit while enprofylline augments some cardio-respiratory stimulant effects of infused adenosine in man.

Adenosine↗
PubMed1987

Hypoxaemia in wheezy infants after bronchodilator treatment.

The response of the bronchi to nebulised salbutamol was measured in five recurrently wheezy infants. Changes in oxygenation (measured by pulse oximeter and transcutaneous PO2 electrodes) and carbon dioxide (measured by transcutaneous PCO2 electrode) were recorded at the same time. Neither nebulised saline nor salbutamol caused any changes in the measurements of airway function. A significant drop in mean oxygen saturation of 2% and of transcutaneous oxygen tension of 1.3 kPa occurred after nebulised salbutamol. No significant change occurred in measurements of transcutaneous carbon dioxide tension, nor was there any significant change in any of these measurements after 2.5 ml of nebulised saline had been given as a control. These results suggest that nebulised salbutamol may cause significant hypoxaemia, in wheezy infants probably by inducing ventilation/perfusion disturbance.

Albuterol↗
PubMed1987

Effect of substance P on cardiovascular and respiratory function in subjects.

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.

Adult↗
PubMed1987

A comparison of 99mTc-DTPA and 113mIn-DTPA aerosol clearances in humans. Effects of smoking, hyperinflation, and in vitro oxidation.

As an index of permeability of the alveolar epithelium, the clearance of an inhaled aerosol of 99mTc-DTPA is increased in several disease states. However, the usefulness of the test to assess the severity of disease is limited because healthy smokers also have abnormally rapid rates of clearance. Because the stability of the 99mTc-DTPA bond might be a contributory factor, we tested the affinity of 99mTc for DTPA in vitro, and in groups of healthy smokers (n = 13) and nonsmokers (n = 7) we measured the clearances of 99mTc-DTPA and 113mIn-DTPA, which have a similar molecular shape and charge. In vitro, sodium hypochlorite or hydrogen peroxide released as much as 98% of free 99mTc from the 99mTc-DTPA complex. When incubated with human neutrophils stimulated with phorbol myristate acetate, between 4 and 7% of free 99mTc-DTPA was released after 30 min, and 12% was released after 60 min. In vivo, the clearances of both 99mTc-DTPA and 113mIn-DTPA in the smokers (n = 13) were faster than in the nonsmokers (n = 7) (p less than 0.05). Within the smokers, the mean 99mTc-DTPA clearance (T1/2 25 +/- 4 min) was faster than the mean 113mIn-DTPA clearance (34 +/- 6 min), (p less than 0.05). For nonsmokers, the difference was smaller (T1/2 99mTc-DTPA, 56 +/- 6; T1/2 113mIn-DTPA, 62 +/- 6) and not significant. During hyperinflation, smokers (n = 8) and nonsmokers (n = 8) both demonstrated an increase in 113mIn-DTPA clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effects of somatostatin, naloxone and prochlorperazine on the control of ventilation in man.

In seven normal subjects the ventilatory responses to progressive isocapnic hypoxia and hyperoxic hypercapnia were measured during rebreathing. During an infusion of somatostatin (10 nmol/min) the mean hypoxic response decreased by 66% (control: -1.6 SD 1.2 litres min-1 %-1 SaO2; somatostatin: -0.6 SD 0.7) but the mean hypercapnic response was unchanged (control: 2.0 SD 0.8 litre min-1 mmHg-1; somatostatin: 2.3 SD 1.2). There was no change in resting VO2 or VCO2 during somatostatin infusion. The opiate antagonist, naloxone (0.1 mg/kg, intravenously), caused little change in either response (mean hypoxic response: -1.7 SD 1.0 litre min-1 %-1 SaO2; mean hypercapnic response: 2.4 SD 0.9 litre min-1 mmHg-1). In five of the subjects the dopamine antagonist, prochlorperazine (10 mg, intravenously), increased the mean hypoxic response by 134% (control: -1.9 SD 1.4 litres min-1 %-1 SaO2; after prochlorperazine: -3.8 SD 1.6; P less than 0.05). The mean hypercapnic response after this drug was also increased (control: 2.1 SD 1.0 litre min-1 mmHg-1; after prochlorperazine: 3.1 SD 1.0) but this change did not achieve significance. The selective effect of somatostatin on the hypoxic response, suggestive of an action on the carotid body, was not inhibited by prior injection of either naloxone or prochlorperazine, and its mode of action remains to be found.

Adult↗
PubMed1986

Somatostatin inhibits the ventilatory response to hypoxia in humans.

The effects of a 90-min infusion of somatostatin (1 mg/h) on ventilation and the ventilatory responses to hypoxia and hypercapnia were studied in six normal adult males. Minute ventilation (VE) was measured with inductance plethysmography, arterial 02 saturation (SaO2) was measured with ear oximetry, and arterial PCO2 (Paco2) was estimated with a transcutaneous CO2 electrode. The steady-state ventilatory response to hypoxia (delta VE/delta SaO2) was measured in subjects breathing 10.5% O2 in an open circuit while isocapnia was maintained by the addition of CO2. The hypercapnic response (delta VE/delta PaCO2) was measured in subjects breathing first 5% and then 7.5% CO2 (in 52-55% O2). Somatostatin greatly attenuated the hypoxic response (control mean -790 ml x min-1.%SaO2 -1, somatostatin mean -120 ml x min-1.%SaO2 -1; P less than 0.01), caused a small fall in resting ventilation (mean % fall - 11%), but did not affect the hypercapnic response. In three of the subjects progressive ventilatory responses (using rebreathing techniques, dry gas meter, and end-tidal Pco2 analysis) and overall metabolism were measured. Somatostatin caused similar changes (mean fall in hypoxic response -73%; no change in hypercapnic response) and did not alter overall O2 consumption nor CO2 production. These results show an hitherto-unsuspected inhibitory potential of this neuropeptide on the control of breathing; the sparing of the hypercapnic response is suggestive of an action on the carotid body but does not exclude a central effect.

Adult↗
PubMed1986

Effect of raised thoracic pressure and volume on 99mTc-DTPA clearance in humans.

Although positive airway pressure is often used to treat acute pulmonary edema, the effects on epithelial solute flux are not well known. We measured independently the effect of 1) positive pressure and 2) voluntary hyperinflation on the clearance of inhaled technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) in six nonsmokers and six smokers. Lung volumes were monitored by inductance plethysmography. Each subject was studied in four situations: 1) low end-expiratory volume (LO-), 2) low volume plus 9 cmH2O continuous positive airway pressure (LO+), 3) high end-expiratory volume (HI-), and 4) high volume plus continuous positive airway pressure (HI+). The clearance half time of 99mTc-DTPA for the nonsmokers decreased from 64.8 +/- 7.0 min (mean +/- SE) at LO- to 23.2 +/- 5.3 min at HI- (P less than 0.05). Positive pressure had no synergistic effect. The mean clearance half time for the smokers was faster than nonsmokers at base line but unaffected by similar changes in thoracic volume and pressure. We conclude that, in nonsmokers, positive airway pressure increases 99mTc-DTPA clearance primarily through an increase in lung volume and that smokers are immune to these effects.

Adult↗
PubMed1986

Effects of adenosine on ventilatory responses to hypoxia and hypercapnia in humans.

Adenosine infusion (100 micrograms X kg-1 X min-1) in humans stimulates ventilation but also causes abdominal and chest discomfort. To exclude the effects of symptoms and to differentiate between a central and peripheral site of action, we measured the effect of adenosine infused at a level (70-80 micrograms X kg-1 X min-1) below the threshold for symptoms. Resting ventilation (VE) and progressive ventilatory responses to isocapnic hypoxia and hyperoxic hypercapnia were measured in six normal men. Compared with a control saline infusion given single blind on the same day, adenosine stimulated VE [mean increase: 1.3 +/- 0.8 (SD) l/min; P less than 0.02], lowered resting end-tidal PCO2 (PETCO2) (mean fall: -3.9 +/- 0.9 Torr), and increased heart rate (mean increase: 16.1 +/- 8.1 beats/min) without changing systemic blood pressure. Adenosine increased the hypoxic ventilatory response (control: -0.68 +/- 0.4 l X min-1 X %SaO2-1, where %SaO2 is percent of arterial O2 saturation; adenosine: -2.40 +/- 1.2 l X min-1 X %SaO2-1; P less than 0.01) measured at a mean PETCO2 of 38.3 +/- 0.6 Torr but did not alter the hypercapnic response. This differential effect suggests that adenosine may stimulate ventilation by a peripheral rather than a central action and therefore may be involved in the mechanism of peripheral chemoreception.

Adenosine↗
PubMed1985

Effect of respiratory apparatus on timing and depth of breathing in man.

The effects on breathing of (1) nose-clips, with and without mouthpieces, (2) tube breathing with incremental dead spaces up to 600 ml, and (3) a Venturi mask with a high air inflow reducing the effective dead space to zero were measured with respiratory inductance plethysmography. The effective dead spaces of the lengths of tubing were 25% smaller than their water-displacement volumes. The principal response to the increase in dead space was an increase in VT without any change in frequency or timing. The increase in VE was 16% greater than the ventilation of the effective dead space. The facemask with a high flow of air did not affect the pattern of breathing. External devices alone (nose-clips, mouthpieces) by themselves brought about a significant increase in VT (+10%, P less than 0.05) and a small drop in frequency, which in the case of a nose-clip alone was large enough to be significant (-15%, P less than 0.05). The increase in DS with the change from nasal to oral breathing may have contributed to the accompanying increase in VT; the fall in frequency with the nose-clip alone might have been caused by stimulation of receptors in the trigeminal area.

Adult↗
PubMed1985

Almitrine increases the steady-state hypoxic ventilatory response in hypoxic chronic air-flow obstruction.

Almitrine, a peripheral chemoreceptor agonist, exerts beneficial effects on blood gases in patients with hypoxic chronic air-flow obstruction, but as these patients exhibit poor ventilatory responses to hypoxia, the mechanism for this improvement is not clear. The effect of a 100-mg dose of almitrine given orally on ventilation and the steady-state hypoxic ventilatory response (HVR) were measured in a randomized, double-blind, placebo-controlled manner in 7 patients with severe hypoxic chronic air-flow obstruction. The isocapnic HVR (delta VE/delta SaO2) was calculated from the changes in ventilation and SaO2 from breathing 60% O2 to breathing air with the addition of CO2 to maintain isocapnia (as estimated from a transcutaneous CO2 electrode). Resting ventilation while breathing air and isocapnic HVR were measured before and 3 h after almitrine or placebo. Almitrine caused no significant change in resting ventilation. There was, however, a large increase in HVR after almitrine (almitrine: -1.5 L/min/%SaO2; range, -0.5 to -3.1; control: -0.4; range, -0.3 to -1.3), but no change after placebo. Almitrine is a powerful stimulant of chemosensitivity and of the hypoxic ventilatory response in chronic hypoxemia, with potential benefit to patients with chronic air-flow obstruction in respiratory failure.

Aged↗