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Biomedical subjects

A Lockhart

Publications and source records attributed to A Lockhart.

At least 127 records · Page 7Linked to original sources
PubMed1984

Inhibition of rat mast cell degranulation by verapamil.

Calcium antagonists, e.g. verapamil, prevent exercise-induced asthma. This protective effect may proceed from inhibition of contraction of bronchial smooth muscle, release of mediators by primary effector cells, e.g. mast cells, or both. Therefore, we studied the inhibitory effect of increasing concentrations of verapamil on both in vitro antigen-induced degranulation and ionophore A23187-induced release of labelled serotonin by rat peritoneal mast cells. There was a dose-dependent inhibition by verapamil of both ovalbumin-induced degranulation of mast cells passively sensitized by incubation with mice IgE-rich serum and ionophore-induced release of tritiated serotonin by mast cells previously incubated with (3H)-5HT; the 50% inhibiting concentration was 1.4 X 10(-4) mol I-1 and 5.2 X 10(-5) mol I-1, respectively. An attractive explanation of our results is that verapamil inhibits the antigen-induced release of mediators by mast cells through its calcium antagonist effect. Our results also suggest that the preventing effect of calcium antagonists on asthma may be multi-factorial since other authors have clearly shown that these drugs inhibit contraction of guinea-pig tracheal smooth muscle in vitro.

Animals↗
PubMed1984

Measurement of pulsatile flows and variable volumes by bolus injection of indicator in a model of the pulmonary circulation.

The reliability and accuracy of the bolus injection-dye dilution technique were assessed for a physiological range of frequencies (13-49 min-1) and stroke volumes (60-160 ml) on a glass model where flows and volumes varied as a preset function of time (n = 320). We found that the technique overestimates flow by about 8% with a 95% confidence interval of +/- 10% for one measurement. Mean transit times are accurate within a +/- 7% confidence interval for one measurement. In a time-dependent flow and volume system this technique measures the mean volume as related to time with fluctuations up to +/- 30% around the mean. Results are independent of time and site of injection. The double injection-single sampling technique gives results that are equivalent to those obtained by single injection and sampling of dye.

Humans↗
PubMed1983

Acute effects of intratracheal administration of platelet-activating factor in baboons.

The bronchomotor effect of intratracheal administration of PAF-acether (60 micrograms X kg -1) was investigated in 37 curarized baboons mechanically ventilated with constant volume and frequency. PAF-acether caused an immediate bronchoconstriction as assessed by a marked increase in peak inspiratory pressure with no change in static pulmonary compliance and chest X-rays. There was a concomitant fall in arterial PO2 and a significant increase in ventilated unperfused lung zones. A decrease of circulating platelets and leucocytes was also observed. Local anesthesia with lidocaine and atropine did not prevent PAF-acether-induced bronchoconstriction although both markedly reduced the bronchial response to histamine. Albuterol significantly reduced the bronchial response to PAF-acether. Pretreatment with aspirin (80 mg X kg -1 iv) did not prevent the bronchoconstriction caused by PAF-acether, and intravenous or intratracheal arachidonic acid caused no bronchial response. Thus the role of cyclooxygenase metabolites of arachidonic acid in PAF-acether-induced bronchoconstriction is unlikely. In conclusion, an acute bronchoconstriction probably not triggered by stimulation of irritant receptors of the airways and associated with aggregation of platelet takes place subsequent to intratracheal administration of PAF-acether. These data suggest that PAF-acether might play a role in the pathogenesis of human asthma.

Anesthesia, Local↗
PubMed1983

Pharmacological properties of almitrine bismesylate.

There is direct evidence in dogs and circumstantial evidence in man that almitrine bismesylate stimulates peripheral chemoreceptors. In anaesthetized dogs, almitrine bimesylate causes an increased activity in afferent fibres from the sinus nerve, in inspiratory neurons of the nucleus tractus solitarius, in expiratory neurons of the nucleus retroambigualis, and in the phrenic nerve. The mechanism whereby almitrine bismesylate stimulates chemoreceptors is poorly understood to date. As a result of chemoreceptor stimulation by almitrine bismesylate , ventilation is higher or unchanged even though PaCO2 has fallen and PaO2 has risen. However, in many patients with chronic obstructive lung disease given almitrine bismesylate , the improvement in arterial blood gases cannot be fully explained by the increased ventilation. This suggests an improved matching of ventilation and perfusion that could be due to diversion of blood flow from poorly towards better ventilated zones. However, all animal experiments have failed to demonstrate such a diversion. Redistribution of ventilation could also explain the improved V/Q matching but has not been unequivocally proven.

Afferent Pathways↗
PubMed1982

Circulatory transport of oxygen in patients with chronic airflow obstruction exercising maximally.

Twenty patients with chronic bronchitis were exercised maximally on a bicycle ergometer. At exhaustion, arterial partial pressure of O2 (Pao2) decreased and that of CO2 (Paco2) increased in 8 patients (Subgroup 1). Arterial PO2 increased and Paco2 did not change in the remaining 12 patients (Subgroup 2). Forced expiratory volume in one second was lower in Subgroup 1 than in Subgroup 2. The decrease in arterial pH and the response of cardiac output were the same in both subgroups. Mixed venous PO2 decreased to 23 mm Hg or less in all patients in Subgroup 1 and in 3 patients in Subgroup 2; it stayed above 25 mm Hg in the remaining 9 patients. Our data imply that the ventilatory response to exercise is insufficient not only in Subgroup 1 but also in Subgroup 2 where the patients failed to hyperventilate in response to exercise-induced acidosis and that an unused oxygen reserve is still present at exhaustion in some patients with chronic airflow obstruction.

Aged↗
PubMed1981

Bronchoconstriction induced by intratracheal administration of platelet-activating factor (PAF-acether) in baboons.

Intratracheal administration of PAF-acether (60 microgram.kg-1) was performed in six premedicated, curarized and mechanically ventilated baboons. Whereas intratracheal administration of an equal amount of solvent (200 microliter of 80 degrees alcohol in 2 ml of saline) caused no measurable changes in lung mechanics, administration of PAF-acether caused an almost immediate bronchoconstriction that was spontaneously reversible within about 30 min. The concomitant fall in platelet count in peripheral blood and reduction of perfusion of ventilated lung territories estimated from the alveolar-arterial difference in CO2 tension provide circumstantial evidence that PAF-acether also caused aggregation of platelets in the lung microcirculation. In keeping with the release of PAF-acether by human alveolar macrophages, our findings suggest that this mediator may play a role in human asthma.

Airway Resistance↗
PubMed1981

Cardiac function in chronic bronchitis: effects of pacing and plasma expansion.

1. We have investigated left ventricular function in 25 selected patients with chronic bronchitis by use of atrial pacing and plasma volume expansion. Nine subjects had a past history of acute respiratory failure. None had either clinical or electrocardiographic signs of coronary heart disease. Paradoxical pulse was absent, since the difference between the highest and lowest systolic arterial pressure throughout the respiratory cycle was 5.4 +/- 1.5 mmHg. 2. During atrial pacing, at a mean rate of 145 +/- 15, about 80% of the predicted maximal rate, none of the patients showed anginal pain or ventricular repolarization abnormality. Cardiac output remained unchanged compared with control values. 3. Plasma volume expansion was achieved by intravenous injection of 1 litre of gelatin over 30 min. Cardiac output, pulmonary wedge pressure and right atrial pressure rose as reported in literature for normal subjects. In four patients cardiac output did not increase although wedge pressure and right atrial pressure did; two of these four patients also had an overshoot in pulmonary wedge pressure just after atrial pacing, suggesting left ventricular dysfunction. Three out of 25 patients had high control right atrial pressures, probably in relation to impaired right ventricular function. No paradoxical pulse occurred during plasma volume expansion. Therefore competition for space in the pericardium between ventricles was unlikely. 4. Our data suggest that left ventricular dysfunction is rare in patients with chronic obstructive pulmonary disease. There was no significant difference between subjects with and without a past history of acute respiratory failure.

Adult↗
PubMed1981

Inhibition of exercise-induced asthma by a calcium antagonist, nifedipine.

Contraction of bronchial smooth muscle and release of mediators by mast cells are involved in asthmatic attacks and are calcium dependent. Therefore, we investigated the effects of a calcium antagonist, nifedipine, in asthma. Ten patients with asthma and documented exercise-induced bronchoconstriction exercised on 2 separate days after single-blind sublingual administration of 20 mg of placebo or nifedipine. The exercise-induced decreases in forced vital capacity, peak expiratory flow, and maximal expiratory flow after exhalation of 50 and 75% of the forced vital capacity were not modified on placebo but were prevented by nifedipine. Ten other asymptomatic patients with asthma and documented exercise-induced bronchoconstriction were studied at rest before and 45 min after nifedipine. The forced vital capacity, peak expiratory flow, and maximal expiratory flows were initially reduced and did not increase after nifedipine. Thus, nifedipine does not modify the basal bronchial tone of patients with asthma but does prevent exercise-induced asthma.

Adolescent↗
PubMed1980

Comparison of hemodynamic effects of furosemide and piretanide in normovolemic patients.

The effects of furosemide and piretanide (Hoe 118) on the pulmonary hemodynamics in 20 patients recovering from uncomplicated myocardial infarctions were compared in a double-blind study. The diuretic effects and half-lives of the two drugs were not significantly different, so that their hemodynamic actions could be compared directly. Both drugs progressively reduced cardiac output and pressures in the pulmonary circulation, whereas systemic vascular resistance increased significantly. Both drugs slightly increased pulmonary blood volume but not significantly. Total blood volume decreased less rapidly than cardiac output, so that the ratio of cardiac output to total blood volume decreased with time. We conclude that both drugs increase venous compliance in normovolemic subjects and probably increase the compliance of pulmonary vessels.

Blood Pressure↗
PubMed1979

Effects of sitting up on pulmonary blood pressure, flow, and volume in man.

Pulmonary vascular pressure, blood flow, and blood volume were measured in the supine and sitting positions in eight subjects with localized lung carcinoma associated with moderate airway obstruction. Supine cardiac output, pulmonary wedge (Ppw) and artery (Ppa) pressure, and pulmonary vascular resistance (PVR) were normal. Circulatory changes in sitting position were also normal: heart rate increased 13 +/- 9% (mean +/- SD); stroke volume fell 21 +/- 15%; cardiac output fell 13 +/- 19%; and arteriovenous O2 difference increased 37 +/- 21%. Neither the difference between mean Ppa and mean Ppw nor the rise of PVR from 92 +/- 25 to 122 +/- 49 dyn.s.cm-5 in sitting position were significant. Pulmonary blood volume (PBV) as measured by a dye-bolus-injection technique fell from 517 +/- 122 ml supine to 360 +/- 43 ml sitting (P less than 0.01). This decrease is best explained by closure of alveolar vessels in the upper part of the lung and by the concomitant cessation of flow in corresponding extra-alveolar vessels, which would prevent distribution of dye in the region. Circumstantial evidence suggests the latter vessels remain open under the large expanding stresses that prevail in the upper lung.

Adult↗