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Biomedical subjects

A D Struthers

Publications and source records attributed to A D Struthers.

At least 271 records · Page 15Linked to original sources
PubMed1985

Selective alpha 2 receptor blockade facilitates the insulin response to adrenaline but not to glucose in man.

The adrenergic nervous system plays an important role in the control of insulin release and animal work suggests that this is mediated by way of alpha 2 adrenoceptors. A specific alpha 2 adrenoceptor antagonist (idazoxan) is now available for use in man and we have studied its effects on insulin release in normal volunteers (a) during the infusion of adrenaline (0.05 micrograms/kg/min) and (b) after an intravenous dose of glucose (20 g). The infusion of adrenaline alone had no significant effect on insulin release while in the presence of idazoxan, insulin release was markedly stimulated by adrenaline. Despite this, adrenaline-induced hyperglycaemia was unaffected by pretreatment with idazoxan. In the second study, pretreatment with either idazoxan or a specific alpha 1 antagonist (prazosin) had no significant effect on either glucose tolerance, glucose-induced insulin release or glucose-induced suppression of glucagon. Intravenous glucose also had no significant effect on pancreatic polypeptide levels. Therefore the effect of adrenaline on insulin release is mediated by way of inhibitory alpha 2 adrenoceptors in the pancreas, while the release of insulin in response to glucose in a resting subject is independent of the alpha-adrenergic system.

Adult↗
PubMed1985

The effect of human atrial natriuretic peptide on urinary sodium and urinary dopamine excretion in man.

Atrial extracts have long been known to produce natriuresis but it is only recently that atrial natriuretic peptide (ANP) itself has been isolated, purified and sequenced. We have now developed a specific radio-immunoassay for ANP and assessed its biological activity by infusing ANP in normal volunteers. Low dose ANP infusion (1.5 pmol/kg per min) produced no haemodynamic or natriuretic effects. High dose ANP infusion (15 pmol/kg per min) produced an increase in plasma immunoreactive ANP levels of 203 +/- 78 pmol/l and caused the urinary sodium excretion to increase from 3.5 +/- 1.6 to 11.0 +/- 7.4 mmol/30 min period (P < 0.05). No haemodynamic effects were seen with this high dose infusion. No changes in urinary dopamine were seen with either ANP infusion. This study shows that ANP is capable of producing a natriuresis in man in the absence of any generalized haemodynamic effects and that ANP may be an important modulator of salt and water balance in man.

Adult↗
PubMed1984

Prediction of response to theophylline in chronic bronchitis.

In chronic bronchitis, intersubject variability in both theophylline pharmacokinetics and pharmacodynamics must be taken into account if the drug is to be used to its best advantage. Both kinds of variability can be integrated into a model which relates the steady state concentration of theophylline to simultaneously measured ventilatory response (most conveniently, the FVC). In a group of 56 patients with chronic bronchitis, the mean +/- s.d. linear response to increasing steady state concentrations of theophylline was 0.04 +/- 0.012 1 microgram-1 ml, starting from a mean +/- s.d. pretreatment FVC of 1.58 +/- 0.791. Using these population parameter values, with or without a pretreatment FVC and/or one steady state concentration -FVC observation, it was possible to predict the degree of response which would be achieved by a smaller group of 20 similar patients. These estimates were obtained using a mathematical procedure based on Bayesian Probability Theory and Maximum Likelihood Estimation. Estimates of the overall response in individual patients allowed prediction of the response at any steady state concentration. These estimates were unbiased and accurate enough for clinical use when they were based on a pretreatment FVC and/or one paired steady state concentration -FVC observation.

Aged↗
PubMed1984

Adrenaline causes hypokalaemia in man by beta 2 adrenoceptor stimulation.

Increased circulating adrenaline produces systemic hypokalaemia by the stimulation of a membrane bound Na/K ATPase. In man, this enzyme appears to be linked to an adrenoceptor of the beta-subtype. We have further studied the subtype of beta-adrenoceptor involved by infusing adrenaline intravenously in normal volunteers after pretreatment with either a selective beta 2 antagonist (ICI 118551) or placebo. During the adrenaline infusion the serum potassium fell from 4.08 +/- 0.21 to 3.32 +/- 0.25 mmol/l (P less than 0.002). This adrenaline induced hypokalaemia was completely blocked by ICI 118551 (3.82 +/- 0.13 to 4.03 +/- 0.22 mmol/l, NS). Adrenaline also caused electrocardiographic changes of T wave flattening (-1.8 +/- 1.5 mm, P less than 0.05) whereas the T wave height increased after ICI 118551 (+ 1.0 +/- 0.9 mm, P less than 0.05). This suggests that adrenaline acts via beta 2 adrenoceptors in man to cause potassium influx and systemic hypokalaemia.

Adrenergic beta-Antagonists↗
PubMed1983

Prior thiazide diuretic treatment increases adrenaline-induced hypokalaemia.

Hypokalaemia is a common finding in acutely ill patients and may be related in part to increased sympathoadrenal activity. In an investigation to determine whether pretreatment with thiazide diuretics causes the serum potassium to fall to an even lower level during increased sympathoadrenal activity, adrenaline was infused into healthy subjects after pretreatment for 7 days with either bendrofluazide (5 mg) or placebo. Thiazide diuretic pretreatment had no effect on the adrenaline-induced changes in blood pressure and heart rate. However, not only was the baseline serum potassium lower after bendrofluazide (3 . 40 mmol/l vs 3 . 83 mmol/l) but the serum potassium also fell to a significantly lower level during adrenaline infusion after bendrofluazide (2 . 73 mmol/l vs 3 . 08 mmol/l). Transient profound hypokalaemia may increase the risk of ventricular arrhythmias in patients on diuretics, and routine monitoring of the resting serum potassium may underestimate this risk.

Adult↗
PubMed1983

The effects of cardioselective and non-selective beta-adrenoceptor blockade on the hypokalaemic and cardiovascular responses to adrenomedullary hormones in man.

Adrenaline was infused intravenously in nine normal volunteers to plasma concentrations similar to those found after myocardial infarction. This study was undertaken on three occasions after 5 days' treatment with placebo or the beta-adrenoceptor antagonists, atenolol or timolol. Adrenaline increased the systolic pressure by 11 mmHg, decreased the diastolic pressure by 14 mmHg, and increased the heart rate by 7 beats/min. These changes were prevented by atenolol. However, after timolol the diastolic pressure rose (+19 mmHg) and heart rate fell (-8 beats/min). Adrenaline caused the corrected QT interval (QTc) to lengthen (0.36 +/- 0.02 s to 0.41 +/- 0.06 s). No significant changes were found in the QTc when subjects were pretreated with atenolol or timolol. The serum potassium fell from 4.06 to 3.22 mmol/l after adrenaline. Serum potassium fell to a lesser extent to 3.67 mmol/l after atenolol and actually increased to 4.25 mmol/l after timolol. Adrenaline-mediated hypokalaemia appears to result from the stimulation of a beta 2-adrenoceptor linked to membrane Na+/K+-ATPase causing potassium influx.

Adult↗
PubMed1983

Effect of intravenous adrenaline on electrocardiogram, blood pressure, and serum potassium.

Increased catecholamines after myocardial infarction may contribute to the development of arrhythmias. We have infused adrenaline intravenously in nine normal volunteers to levels similar to those seen after myocardial infarction. Adrenaline caused an increase in systolic blood pressure, a decrease in diastolic blood pressure, and an increase in heart rate. Adrenaline also produced a decrease in T wave amplitude and an increase in the QTc interval. The serum potassium fell dramatically during the adrenaline infusion from a control value of 4.06 mmol/l to 3.22 mmol/l. Hypokalaemia after myocardial infarction is associated with an increased incidence of ventricular arrhythmias. Thus, circulating adrenaline may increase the frequency of arrhythmias both directly via changes in ventricular repolarisation and indirectly via adrenaline induced hypokalaemia.

Adult↗
PubMed1983

Metabolic and haemodynamic effects of increased circulating adrenaline in man. Effect of labetalol, an alpha and beta blocker.

To simulate increased sympathoadrenal activity adrenaline was infused in normotensive subjects to achieve plasma adrenaline concentrations similar to those seen after myocardial infarction or hypoglycaemia. Adrenaline was infused after pretreatment for five days with labetalol 200 mg twice daily or placebo given in a random order. The rise in systolic blood pressure and the fall in diastolic blood pressure observed after the infusion of adrenaline (0.06 micrograms/kg/min) were prevented by labetalol and no increase in blood pressure was seen. Adrenaline infusion after pretreatment with placebo caused a profound fall in the serum potassium concentration (4.12-3.20 mmol(mEq)/l). Pretreatment with labetalol completely blocked adrenaline induced hypokalaemia (3.92-3.95 mmol(mEq)/l). Adrenaline induced T wave flattening and QTc prolongation were also prevented by labetalol. Thus labetalol can prevent the electrocardiographic, haemodynamic, and hypokalaemic effects of increased circulating adrenaline in man. The combination of alpha and beta blockade appears to be required to block the haemodynamic effects of adrenaline, and labetalol may, therefore, be useful in controlling both the metabolic and circulatory responses during increased sympathoadrenal activity.

Adult↗
PubMed1983

Calcium antagonists and hormone release: effect of nifedipine on luteinizing hormone-releasing hormone and thyrotropin-releasing hormone-induced pituitary hormone release.

In vitro evidence suggests that calcium is involved in the release of anterior pituitary hormones. Therefore, we studied the effect of the slow calcium channel blocker or calcium antagonist nifedipine on the FSH and LH responses to LRH and the TSH and PRL responses to TRH in vivo. Nine normal male subjects were studied on two occasions, and nifedipine (20 mg, by mouth, or matching placebo) was administered in a randomized single blind manner. Blood pressure and heart rate were measured at 0 and 30 min. The patients then received TRH (200 micrograms) and LRH (100 micrograms) iv. Blood levels of FSH, LH, TSH, and PRL were measured by RIA at 0, 30, 50, 60, and 120 min. Nifedipine lowered diastolic blood pressure significantly (--12 +/- 8 mm Hg; P less than 0.005) and increased heart rate (+ 17 /*- 10 beats/min; P less than 0.005), but had no effect on either baseline hormone levels or the incremental response of any hormone to its secretagogue. In contrast to the results of previous studies with verapamil, nifedipine does not inhibit the release of pituitary hormones. More information is required on the precise intracellular actions of these drugs before they can be used to study the role of calcium in hormone release. Nifedipine, however, may be less likely to influence pituitary function than verapamil.

Adult↗
PubMed1983

The haemodynamic effects of labetalol under conditions of increased levels of circulating catecholamines.

Adrenaline was infused into normal volunteers to produce plasma adrenaline levels similar to those found in acute myocardial infarction. These infusions were performed after pretreatment with labetalol or placebo. Adrenaline produced an increase in systolic blood pressure, a decrease in diastolic blood pressure and an increase in heart rate. All of these haemodynamic effects were blocked by labetalol. In particular, no increase in diastolic blood pressure was seen as occurs during increased sympatho-adrenal activity in the presence of non-sensitive beta-blockade. Thus labetalol maintains a different haemodynamic profile from non-selective beta-blockade during increased sympatho-adrenal activity.

Blood Pressure↗
PubMed1983

Nifedipine--studies on its mechanism of action and interaction with other circulatory control mechanisms in man.

Calcium antagonists such as nifedipine have been shown to lower blood pressure alone or in combination with other drugs in mild, moderate and severe hypertension. It is likely that the antihypertensive action depends on modification of calcium dependent coupling of excitation and contraction in peripheral vascular smooth muscle. Acute effects of nifedipine are associated with reflex mediated increases in sympathetic tone and plasma renin activity while in the long term these effects are less prominent. Nifedipine does not interfere with depressor mechanisms mediated by prostaglandins or peripheral vascular beta 2 receptors. In contrast peripheral pressor mechanisms including those mediated by angiotensin II and noradrenaline are antagonised. The long term efficacy of nifedipine in hypertension probably depends on its direct vasodilator effect, the preservation of depressor mechanisms and attenuation of reflex responses and direct and indirect pressor mechanisms.

Adult↗
PubMed1982

The effect of glyceryl trinitrate ointment on heart rate--corrected systolic time intervals in angina pectoris.

1 Individual systolic time intervals (STI) v heart rate regression equations were determined using small doses of intravenous atropine in seven patients with angina pectoris. 2 Regression lines of the form LVET = A + B.HR and QS2 = C + D.HR were calculated. There was no significant correlation between PEP and HR. The values of parameters A C and D were significantly different from a group of previously studied normal volunteers. 3 STI changes were recorded for 5 h after the application of GTN or placebo ointment. The active drug caused shortening of LVET and QS2 with the peak effect occurring between 105 and 180 min. After 180 min neither LVET nor QS2 were significantly shortened. There was no significant effect on PEP or heart rate.

Aged↗