Plasma catecholamine responses to change of posture in alcoholics during withdrawal and after continued abstinence from alcohol

Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2-7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2-7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.     

The Role of the Beta-Adrenergic Receptor in the Secretion of Gastrin: Studies in Normal Subjects and in Patients with Duodenal Ulcers

Intravenous infusion of isoproterenol, a beta-adrenergic receptor stimulatory agent, increased serum gastrin concentration significantly more in patients with a duodenal ulcer than in healthy subjects. The rise in pulse rate, blood glucose concentration and in serum insulin was the same in both groups of subjects. Gastrin secretion was also increased significantly more in the patients than in the control subjects after a beef-meal. Basal serum gastrin concentrations were higher in the patients than in the control subjects and correlated to the rise in serum gastrin during both tests in the patients with a duodenal ulcer. Isoproterenol and meal stimulated gastrin secretion, expressed as percent of the basal value, were twice as high in the patients as in the control subjects. The combined administration of isoproterenol and the meal had an additive effect on the rise in serum gastrin. Isoproterenol stimulated gastrin secretion was completely suppressed by propranolol, a beta-adrenergic receptor blocking agent, which had no effect on meal stimulated gastrin secretion. It is concluded that the mechanism of the hypersecretion of gastrin in patients with a duodenal ulcer did not involve a specific abnormality of the beta-adrenergic receptor or the receptor which recognized proteins and their digested products. There is no established role of beta-adrenergic receptor activity in the hypersecretion of gastrin in patients with duodenal ulcers. It is suggested that the beta-adrenergic receptor may have some yet unknown function unrelated to the acute secretory response of gastrin.     

Role of circulating somatostatin in regulation of gastric acid secretion, gastrin release, and islet cell function. Studies in healthy subjects and duodenal ulcer patients.

Studies were designed (a) to determine whether somatostatin is released into the circulation after meals in sufficient amounts to regulate gastric or pancreatic islet function in humans and (b) to investigate the possible role of somatostatin in the pathogenesis of duodenal ulcer disease. Mean plasma somatostatin-like immunoreactivity (SLI) increased from 6.2 +/- 1.5 pg/ml to a peak level of 13.8 +/- 1.3 pg/ml in eight healthy subjects after a 1,440-cal steak meal (P less than 0.005). When somatostatin-14 was infused intravenously, basal and food-stimulated gastric acid secretion and also basal and food-simulated plasma insulin and glucagon concentrations were reduced significantly at mean plasma SLI concentrations within the range seen after a meal. Thus, the amount of somatostatin reaching the systemic circulation after a steak meal was sufficient to inhibit gastric acid secretion and islet cell function. On the other hand, basal and food-stimulated plasma gastrin concentrations were reduced by intravenous somatostatin only at plasma SLI concentrations that were several-fold greater than post-prandial SLI concentrations. Although duodenal ulcer patients had significantly higher basal, food-stimulated, and peak pentagastrin-stimulated gastric acid secretion rates than healthy controls, duodenal ulcer patients and controls had nearly identical basal and food-stimulated SLI concentrations. Moreover, food-stimulated gastric acid secretion and gastrin release were inhibited by intravenous somatostatin to the same extent in ulcer patients and controls. These studies suggest that duodenal ulcer patients release normal amounts of somatostatin into the circulation and that target cells controlling acid secretion and gastrin release are normally sensitive to somatostatin in these patients.     

Inhibition of gastrin secretion by hypertonic solutions in patients with pernicious anaemia and duodenal ulcer

Abstract. Serum gastrin increased in patients with pernicious anaemia after a beef-meal, but decreased after an oral load of glucose, xylose or sodium chloride. 50 g of glucose and 25 or 75 g of xylose suppressed serum gastrin to appoximately 40% of basal values at 60 min and were slightly more effective than 10 g of sodium chloride.
There was no rise in beef-meal stimulated serum gastrin concentration in vagotomized patients and only a slight rise in two patients with duodenal ulcer when an oral dose of 10 g of sodium chloride was given together with the beef-meal. 25 g of xylose suppressed basal serum gastrin concentration significantly in six vagotomized patients.
Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in all subjects examined. Further studies indicated, however, that vasopressin was only effective when pharmacological plasma concentrations were attained.
The inhibitory effects of 10 g of glucose given orally and intraduodenally were compared in six patients with pernicious anaemia. Serum gastrin concentration decreased approximately to the same extent in both experiments.
It is concluded that the inhibitory effect of glucose on gastrin secretion most likely is mediated hormonally via osmo-receptors located in the small intestine.     

Effect of bromocriptine treatment on prolactin, noradrenaline and blood pressure in hypertensive haemodialysis patients

Bromocriptine (2.5 mg/day orally) produced a significant fall in supine mean arterial pressure in nine hypertensive haemodialysis patients with high serum prolactin levels, without causing significant changes in heart rate. On bromocriptine, there was a significant decrease in the mean value of both serum prolactin and plasma noradrenaline, without significant changes in the mean value of plasma renin activity. A significant relationship was found between the changes in supine plasma noradrenaline and the changes in supine mean arterial pressure induced by bromocriptine. The increase in mean arterial pressure in response to the tilt test was greater on bromocriptine than on placebo although the changes in plasma noradrenaline were reduced by bromocriptine. Similar results were observed during the cold pressor test. These findings suggest that the arterial pressure-lowering effect of bromocriptine is related to the reduction in sympathetic out-flow. The parallel decrease in serum prolactin raises the question of the possible involvement of dopaminergic mechanisms in the development of hypertension in our patients. Moreover, bromocriptine seems to enhance the vascular response to endogenous noradrenaline.     

Measurement of blood cortisol and acid output in patients with duodenal ulceration and normal subjects during insulin hypoglycaemia

The blood cortisol and gastric acid responses to insulin hypoglycaemia were investigated in 18 healthy control subjects and 14 patients with endoscopically proven duodenal ulceration. In both controls and patients, insulin hypoglycaemia caused blood cortisol and acid output to rise and peak simultaneously, the rises being significantly greater in patients with duodenal ulcer than in control subjects. The peak acid output and the base to peak cortisol increments were also found to be significantly greater in patients with duodenal ulcer than in control subjects (P less than 0.001 and P less than 0.005 respectively). We conclude that insulin hypoglycaemia causes stimulation of the sympathetic and parasympathetic nervous systems and of the hypothalamo-pituitary-adrenal axis, resulting in the simultaneous elevation of gastric juice acidity and blood cortisol levels. We have shown that synchronous rises in gastric acid and blood cortisol occur during insulin hypoglycaemia and that these rises are greater in patients with duodenal ulcer.     

Comparison of acid secretory responsiveness to gastrin heptadecapeptide and of gastrin heptadecapeptide pharmacokinetics in duodenal ulcer patients and normal subjects.

Serum gastrin concentrations and gastric acid secretion were measured during intravenous infusion of gastrin heptadecapeptide (G-17) (0, 7, 22.1, 70, 221, and 700 pmol/kg X h) in 15 duodenal ulcer patients and 15 healthy controls. Ulcer patients developed higher serum gastrin concentrations during G-17 infusion due to nearly twofold slower clearance of gastrin (8.8 vs. 15.7 ml/kg X min; P less than 0.01). Despite slower clearance of G-17, ulcer patients had plasma elimination half-times for G-17 similar to controls (6.0 vs. 6.1 min, respectively). Thus, calculated volume of distribution for G-17 was lower in ulcer patients than controls (78.5 vs. 140.7 ml/kg; P less than 0.025). For any serum gastrin during gastrin-17 infusion, acid secretion (millimoles per hour) was higher in ulcer patients than in controls. However, when acid secretion was expressed as a percentage of peak acid output to G-17 (to correct for differences in parietal cell mass), curves relating acid secretion to serum gastrin were identical in ulcer patients and controls.     

Serum gastrin response to acute and chronic hypercalcaemia in man: studies on the value of calcium stimulated serum gastrin levels in the diagnosis of Zollinger-Ellison syndrome

In this study the effect of calcium infusion over 3 h without gastric aspiration on serum gastrin was determined in fifteen normal subjects, ten patients with duodenal ulcer, nine with stomal ulcer, five with total gastrectomy, six with achlorhydria and sixteen with proved or presumed Zollinger-Ellison (ZE) syndrome. Serum gastrin only rose significantly in the patients with ZE-syndrome or achlorhydria. An increase of above or below 50% of basal value seems to be a valuable criterion by which to differentiate between patients with and without ZE-syndrome. Serum gastrin levels in forty-four patients with chronic hypercalcaemia (72+/-24 pg/ml, mean+/-SD) were not significantly different from the levels in 100 normal subjects (66+/-18 pg/ml; P greater than 0.10). However, in one patient with ZE-syndrome and in two patients with achlorhydria serum gastrin values were markedly higher during chronic hypercalcaemia than during normocalcaemia. It is concluded that acute or chronic hypercalcaemia without gastric aspiration does not lead to hypergastrinaemia in the absence of ZE-syndrome or achlorhydria.     

Interrelationship between gastric acidity and gastrin concentration in patients with duodenal or gastric ulcer and in healthy subjects

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.     

Plasma noradrenaline and adrenaline concentrations and dopamine-beta-hydroxylase activity in patients with shock due to septicaemia, trauma and haemorrhage

Plasma adrenaline and noradrenaline concentrations and dopamine-beta-hydroxylase activities were measured in patients with septicaemic, traumatic or haemorrhagic shock. Irrespective of the type of shock plasma adrenaline and noradrenaline concentrations were increased above the normal range. This is in keeping with the clinical features of increased sympathetic nervous system and adrenal medullary activity present in these patients. Plasma dopamine-beta-hydroxylase activities were within the normal limits in all forms of shock indicating the poor relationship of this measurement to sympathetic nervous system activity. In patients who died plasma noradrenaline concentrations remained persistently elevated above normal while in those who survived there was a rapid decline towards the normal range.     

Do increased catecholamines and plasma methionine enkephalin in cirrhosis promote bleeding oesophageal varices?

Increased sympathetic tone and adrenal medullary activity in hepatic cirrhosis may promote portal hypertension. We suggest that they may be imperfect homeostatic mechanisms attempting to maintain systemic arterial pressure in response to chronic vasodilatation and that small, endogenous opioid peptides may play a part in this vasodilatation. As initial investigation of this hypothesis, we measured noradrenaline (an indicator of sympathetic tone), adrenaline and methionine enkephalin in the plasma of patients with cirrhosis with oesophageal varices which had or had not bled previously, patients with cirrhosis without varices, patients with acute liver disease and controls. In patients with cirrhosis, noradrenaline, adrenaline and methionine enkephalin were all greatest in those with oesophageal varices which had previously bled. In this group, noradrenaline correlated strongly with the widely used prognostic guide, Pugh's modification of Child's classification. In patients with acute liver disease, methionine enkephalin and adrenaline were increased six- and four-fold respectively. However, noradrenaline was normal, suggesting that increased sympathetic tone in cirrhosis may develop gradually. The use of opioid antagonists may enable determination of whether elevated plasma opioid peptides in cirrhosis stimulate the increase in sympathetic tone and plasma adrenaline, and promote bleeding oesophageal varices.     

The role of adrenaline and of the vagus in gastrin release and acid secretion in dogs

Serum gastrin, gastric acid secretion and plasma adrenaline in response to intravenous injection of 2-deoxy-D-glucose and to insulin were measured in six dogs with gastric fistulae before and after denervation of the antrum and the intestine (antral-intestinal vagotomy). Serum gastrin and gastric acid secretion were also measured in the same dogs during intravenous infusion of adrenaline in doses which produced an elevation of plasma adrenaline to levels occurring during hypoglycaemia and after the injection of 2-deoxy-D-glucose. Antral-intestinal vagotomy reduced basal gastrin concentration slightly and basal gastric acid secretion considerably. The rise in serum gastrin in response to 2-deoxy-D-glucose and hypoglycaemia was abolished while the increase in gastric acid secretion was reduced after antral-intestinal vagotomy. Beef meal-stimulated gastrin secretion was the same before and after vagotomy. Intravenous infusion of adrenaline had no effect on either serum gastrin or gastric acid secretion. It is concluded that in the dog, in contradistinction to man, gastrin release after insulin is dependent on an intact vagus. Release of gastrin by adrenaline in the dog does not appear to be physiological since it is not achieved by the amount of adrenaline released in response to hypoglycaemia.     

Cardiovascular Control in Recently Injured Tetraplegics in Spinal Shock

Cardiovascular control was studied in five tetraplegic patientswith physiologically complete cervical spinal cord transections.All had been injured less than two weeks previously and werein spinal shock. Blood pressure, heart rate, and plasma noradrenalineand adrenaline were measured at rest and during and after bladderstimulation and application of cold stimuli to skin below thelevel of the lesion. In three patients the cardiovascular responsesto intravenously infused 1-noradrenaline and to the Valsalvamanoeuvre were recorded. Measurements were also made in sixchronic tetraplegic patients (in whom reflex spinal cord activityhad returned) at rest, and during and after bladder stimulation,and in six normal subjects at rest. Average resting blood pressure in the recently injured tetraplegicswas 130/57 (mean 81) mmHg, in the chronic tetraplegics 107/55(mean 73) mmHg and in normal subjects 122/82 (mean 95) mmHg.Average resting heart rate was 64, 73 and 77 beats/min in thethree groups respectively. Resting plasma noradrenaline andadrenaline levels in both the recently injured and chronic tetraplegicswere lower than in normal subjects. In the recently injured tetraplegics bladder stimulation causedminimal changes in blood pressure, heart rate and plasma noradrenalineand adrenaline levels. In the chronic tetraplegics simliar stimulationcaused marked hypertension, bradycardia and elevation in plasmanoradrenaline but not adrenaline levels. Cold stimuli in therecently injured tetraplegics did not change blood pressureor heart rate. In the recently injured tetraplegics intravenous infusion of1-noradrenaline resulted in greater elevation in blood pressurethan normal. There was a decrease in heart rate. One patientwas able to perform the Valsalva manoeuvre. His blood pressureresponses were consistently abnormal (‘blocked’Valsalva). It is concluded that recently injured tetraplegics in spinalshock have normal systolic blood pressure but lower diastolicblood pressure than normal subjects. Resting plasma noradrenalineand adrenaline levels are also lower than in normal subjectsand this suggests diminished sympathetic nervous activity atrest. The small cardiovascular and catecholamine responses tocutaneous and visceral stimuli suggest feeble or absent spinalsympathetic cardiovascular reflexes in spinal shock. The abnormalblood pressure responses to infusion of noradrenaline and tothe Valsalva manoeuvre indicate impaired blood pressure homeostaticreflexes.     

Choice of control groups in the appraisal of sympathetic nervous activity in essential hypertension

1. Plasma noradrenaline concentrations were similar in normotensive and hypertensive outpatients, but were significantly lower in laboratory control subjects. 2. Standing plasma noradrenaline concentrations were similar in all three groups. 3. Urinary vanillyl mandelic acid, catecholamines and metanephrines were also similar in the normotensive and hypertensive groups. 4. Laboratory controls, possibly because of familiarity with the techniques of sphygmomanometry and blood sampling, may attain a 'basal' resting level of sympathetic nervous discharge more readily and rapidly than subjects who are unfamiliar with such procedures. 5. After orthostatic stimulation by standing for 2 min, the activity of the sympathetic nervous system, as determined by pulse rate and plasma noradrenaline concentrations, was similar in the three groups, despite the lower starting values in the laboratory staff. 6. The absence of differences in plasma noradrenaline or urinary catecholamine and metabolite concentrations does not support the hypothesis of excessive sympathetic nervous activity in essential hypertension.     

The contribution of the renin-angiotensin system to limb vasoregulation in patients with heart failure: observations during orthostasis and alpha-adrenergic blockade

1. In patients with congestive heart failure, both the sympathetic nervous system and renin-angiotensin system are often stimulated. In order to assess the contribution of the renin-angiotensin system to limb vascular resistance, the forearm haemodynamic response to captopril was studied in 13 patients with heart failure. 2. Seven subjects were studied while supine and during 60 degrees head-up tilt. To eliminate alpha-adrenergic effects, six additional patients with heart failure were pretreated with intra-arterial phentolamine and then given captopril. Venous occlusion plethysmography was used to determine forearm blood flow and forearm vascular resistance. 3. Tilt did not significantly increase pretreatment plasma renin activity or plasma noradrenaline concentration, nor did it decrease forearm blood flow. Furthermore, captopril did not alter forearm vascular resistance during supine or upright posture. During the phentolamine infusion, however, captopril reduced forearm vascular resistance by 19% (P < 0.05). 4. Despite increased plasma renin activity, captopril did not cause forearm vasodilatation during supine or upright posture in these patients with heart failure. When the contribution of the sympathetic nervous system was eliminated, captopril decreased forearm vascular resistance. Therefore, in patients with congestive heart failure, the sympathetic nervous system is important in limb vasoregulation, and the contribution of the renin-angiotensin system is apparent only after alpha-adrenergic blockade.     

EFFECTS OF KETANSERIN ON CARDIOVASCULAR, SYMPATHO-ADRENAL AND ENDOCRINE SYSTEMS DURING PHYSICAL EXERCISE IN MAN

Blood pressure, heart rate, oxygen consumption, plasma concentrations of catecholamines, renin, aldosterone and lactate were measured in 6 normotensive volunteers during a randomized cross-over study of oral ketanserin (20 mg X 7) and placebo; measurements were made at rest and during maximal dynamic exercise on a bicycle ergometer. At rest ketanserin reduced blood pressure without modifying heart rate or plasma noradrenaline and adrenaline. Duration of exercise and blood lactate levels did not differ between the ketanserin and the control group. During exercise only systolic blood pressure was significantly decreased on ketanserin at maximal work rate whereas heart rate did not change. Plasma noradrenaline was significantly increased and plasma aldosterone significantly decreased during exercise in ketanserin-treated subjects whereas plasma renin activity and plasma adrenaline remained unchanged. Finally, under ketanserin oxygen consumption during exercise was reduced. The results suggest that ketanserin might interfere with the sympathetic nervous system and aldosterone secretion in man.     

The relation between functioning parietal cell and gastrin cell masses in two groups of duodenal ulcer patients.

1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects. 2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess. 3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid "normosecretors" and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low. 4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hyper-secretors but the values for the latter were not different from normal subjects. 5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups. 6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients. 7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass.     

Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humans in vivo

Plasma NEFA (non-esterified fatty acid) concentrations are elevated in patients with obesity. In the present study we first aimed to provide an integral haemodynamic profile of elevated plasma NEFAs by the simultaneous assessment of blood pressure, pulse wave velocity, FBF (forearm blood flow) and sympathetic nervous system activity during acute elevation of NEFAs. Secondly, we hypothesized that NEFA-induced vasodilation is mediated by adenosine receptor stimulation. In a randomized cross-over trial in healthy subjects, Intralipid was infused for 2 h to elevate plasma NEFAs. Glycerol was administered as the Control infusion. We assessed blood pressure, pulse wave velocity, FBF (using venous occlusion plethysmography) and sympathetic nervous system activity by measurement of noradrenaline and adrenaline. During the last 15 min of Intralipid/Control infusion, the adenosine receptor antagonist caffeine (90 microg x min(-1) x dl(-1)) was administered into the brachial artery of the non-dominant arm. Compared with Control infusion, Intralipid increased pulse wave velocity, SBP (systolic blood pressure) and pulse pressure, as well as FBF (from 1.8+/-0.2 to 2.7+/-0.6 and from 2.3+/-0.2 to 2.7+/-0.6 ml x min(-1) x dl(-1) for Intralipid compared with Control infusion; P<0.05, n=9). Although in a positive control study caffeine attenuated adenosine-induced forearm vasodilation (P<0.01, n=6), caffeine had no effect on Intralipid-induced vasodilation (P=0.5). In conclusion, elevation of plasma NEFA levels increased pulse wave velocity, SBP and pulse pressure. FBF was also increased, either by baroreflex-mediated inhibition of the sympathetic nervous system or by a direct vasodilating effect of NEFAs. As the adenosine receptor antagonist caffeine could not antagonize the vasodilator response, this response is not mediated by adenosine receptor stimulation.     

Effects of oxygen withdrawal on catecholamine release in patients on home oxygen therapy

1. Long-term oxygen therapy in appropriate patients prolongs survival and corrects neuropsychological function. Some tests of mental function paradoxically improve during short periods of oxygen withdrawal in patients on long-term oxygen therapy, although the mechanism of this response is unknown. 2. To evaluate the effects of transient hypoxaemia on plasma adrenaline and noradrenaline levels, we studied eight oxygen-dependent patients who underwent either a 4 h period of oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on 2 separate days. 3. Plasma noradrenaline did not differ at baseline between study days. During normoxic conditions, plasma noradrenaline levels did not increase significantly with time. By contrast, under hypoxic conditions, plasma levels of noradrenaline rose significantly from 0 to 4 h (P less than 0.05). The magnitude of the noradrenaline response was correlated with baseline noradrenaline such that subjects with the highest resting levels had the largest increase during hypoxia (r = 0.95, P less than 0.001). 4. Plasma adrenaline did not differ at baseline between study days and there were no significant effects of hypoxia on plasma adrenaline levels. 5. We conclude that the sympathetic nervous system, but not the adrenal medulla, is stimulated in chronically oxygen-dependent subjects made acutely hypoxaemic. The magnitude of this stimulation appears to be related to the state of sympathetic nervous system activity at baseline. Improvement in some tests of mental function during transient periods of oxygen withdrawal may be due to non-specific arousal caused by a catecholamine surge.     

Cardiac and whole-body [3H]noradrenaline kinetics during adrenaline infusion in man.

1. To investigate the possible role of adrenaline as a modulator of noradrenaline release from the sympathetic nervous system, the responses of cardiac and whole-body noradrenaline kinetics to intravenous infusions of adrenaline (30 ng min-1 kg-1) and matching saline placebo were determined at rest and during supine bicycle exercise in 16 patients undergoing cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 72 h. 2. At rest and compared with placebo, infusion of adrenaline was associated with a small increase in arterial plasma noradrenaline from 211 +/- 29 pg/ml to 245 +/- 29 pg/ml (P less than 0.05). Increases in whole-body noradrenaline spillover to arterial plasma were larger (from 282 +/- 40 ng min-1 m-2 to 358 +/- 41 ng min-1 m-2, P less than 0.01) and there was a trend towards an increase in whole-body noradrenaline clearance. Cardiac noradrenaline clearance was modestly increased during adrenaline infusion, but cardiac noradrenaline spillover was not altered despite increases in heart rate and coronary sinus plasma flow. Adrenaline infusion was associated with symptomatic myocardial ischaemia in four of 14 patients with coronary heart disease. 3. Supine bicycle exercise was associated with significant increases in peripheral noradrenaline concentrations and in cardiac and whole-body noradrenaline spillover. The increases on exercise were not significantly different for these variables during saline and adrenaline infusions. 4. Infusion of adrenaline to produce 'physiological' increases in plasma adrenaline concentration was associated with an increase in total noradrenaline release, as assessed by whole-body noradrenaline spillover to plasma.(ABSTRACT TRUNCATED AT 250 WORDS)