Atrial Natriuretic Peptide during Exercise in Patients with Coronary Heart Disease before and after Single Dose Atenolol and Acebutolol

Plasma atrial natriuretic peptide (ANP) was measured during dynamic exercise in 10 patients with coronary heart disease before and after single dose atenolol 50 mg and acebutolol 200 mg, respectively. Systolic blood pressure, heart rate and the rate-pressure product increased during exercise before and after β-blockade, but levels were lower after β-blockade. Plasma ANP levels at rest were unchanged after atenolol, but rose after acebutolol (p<0.01). During exercise plasma ANP increased significantly both before and after β-blockade, but plasma ANP levels were higher after acebutolol at all workloads (p<0.05), whereas plasma ANP levels after atenolol were higher at 125 W exclusively (p<0.05). The augmented ANP levels during exercise after β-blockade probably reflect catecholamine-stimulated ANP release, whereas the elevated plasma ANP levels after acebutolol at rest might be a β-adrenoceptor-mediated ANP release due to the intrinsic sympathomimetic effect of acebutolol.     

Increased Plasma Free Dopamine after Treatment with Atenolol and Oxprenolol in Essential Hypertension

ABSTRACT. In 19 men aged 50 with essential hypertension, 18 weeks' treatment with atenolol (n=9) or oxprenolol (n=10) increased supine plasma free dopamine concentrations by 78% (p<0.05) and 121 % (p<0.001) respectively. Increments in plasma dopamine were observed in all patients except for one treated with atenolol. Supine peripheral venous adrenaline and noradrenaline concentrations were not influenced by β-blockade. The mechanism and significance of the present elevation of plasma free dopamine by β-blockade are unknown. However, increased plasma free dopamine may be involved in the hypotensive effect of chronic β-adrenergic blockade, both β-1 selective and non-selective, and may lend further support to decreased dopaminergic activity in essential hypertenison.     

The Effect of β-Blockade on Gastric Acid Secretion,Gastrin Release,and Plasma Catecholamine Concentrations during Modified Sham Feeding in Duodenal Ulcer Patients

The effects of β-blockade (propranolol, 100 mg orally) on gastric acid output and on circulating levels of gastrin, adrenaline, noradrenaline, and dopamine during modified sham feeding (MSF) were investigated by a randomized, double-blind method in six patients with asymptomatic duodenal ulcer disease. No differences occurred in peak acid output during MSF, whereas basal acid output was significantly suppressed by β-blockade and peak acid output was unaffected. Basal gastrin concentration was lower during β-blockade but rose in response to MSF. Without β-blockade serum gastrin levels were unaffected by MSF. Plasma catecholamine concentrations were not affected by the β-blockade. It is concluded that acid output and gastrin release in response to MSF, unlike that to insulin hypoglycaemia, is not influenced by β-adrenoceptor blockade.     

Potentiation by adrenaline of agonist-induced responses in normal human platelets in vitro

Adrenaline is not a true platelet agonist, but enhances aggregation, dense granule secretion, and phospholipase C induced by other agonists. In the present work we investigated the effect of adrenaline on other platelet responses. It strongly potentiated ADP-induced shape change in platelet-rich plasma, particularly when aggregation was prevented by EDTA. The degree of potentiation increased with increasing concentrations of ADP. Thrombin-induced α-granule secretion, measured by the release of fibrinogen in gel-filtered platelets, was also potentiated by adrenaline at thrombin concentrations above 0.05 U/ml. In contrast, adrenaline had little effect on thrombin-induced secretion of β-acetyl-hexosaminidase and potentiated very little liberation of arachidonate at high thrombin concentrations. When autocrine stimulation was inhibited by the removal of secreted ADP by creatine phosphate/creatine phosphate kinase and specific blocking of the thromboxane A(2) and fibrinogen receptors, the potentiation of thrombin-induced ADP?+?ATP secretion by adrenaline was reduced and this reduction was mostly due to the blocking of the thromboxane A(2) receptor. Protein tyrosine phosphorylation by both thrombin and collagen was reduced by adrenaline, and inhibitors of autocrine stimulation counteracted this reduction.     

Heart rate variability and circulating catecholamine concentrations during steady state exercise in healthy volunteers.

OBJECTIVES--To assess whether exercise induced suppression of heart rate variability in the low frequency domain (0.06-0.15 Hz) is related to the increase in circulating catecholamine concentrations. DESIGN--Randomised crossover trial of three exercise tests characterised by different workloads. Pharmacological simulation of exercise-induced changes in vagal and sympathetic activity. PARTICIPANTS--Six healthy men with a mean age of 31.2 (SD 3.0) years. INTERVENTIONS--Three different workloads of steady state cycling ergometry: control state without cycling, cycling at a target heart rate of 100 beats/min, and cycling at a target heart rate of 150 beats/min. Intravenous infusion of atropine (target heart rate 100 beats/min) followed by the additional infusion of adrenaline and noradrenaline. MAIN OUTCOME MEASURES--Fast Fourier analysis of heart rate variability; blood pressure; and venous plasma concentrations of lactate, adrenaline, and noradrenaline. RESULTS--During the control exercise period there were no changes in the assessed variables compared with the preceding resting period. During exercise at a heart rate of 100 beats/min systolic blood pressure increased and heart rate variability decreased. During exercise at a heart rate of 150 beats/min systolic blood pressure and lactate, adrenaline, and noradrenaline concentrations increased. In addition, low frequency (LF) was lower than during exercise at 100 beats/min, high frequency (HF 0.15-0.80 Hz) resembled that during exercise at 100 beats/min, and diastolic blood pressure was reduced. Infusion of atropine caused no changes in blood pressure or plasma concentrations of lactate, adrenaline, and noradrenaline and decreased heart rate variability. The additional infusion of adrenaline and noradrenaline completely suppressed heart rate variability and increased blood pressure. CONCLUSIONS--The reduction in LF and HF during exercise at a heart rate of 100 beats/min, which is not characterised by increased plasma catecholamine concentrations, and during atropine infusion suggests that heart rate variability in the supine state is largely influenced by vagal activity. The additional reduction in LF during exercise at 150 beats/min and during catecholamine infusion may reflect a negative feedback of circulating catecholamines on the sympathetic control of heart rate.     

Neither physical exercise nor α1- and β-adrenergic blockade affect plasma endothelin concentrations

Endothelins (ET) are recently discovered vasoconstrictor agents released from endothelial cells and have been the object of intense investigation by researchers. Many of the factors that seem to influence the release of ET are modified by prolonged exercise. The purpose of this study was to investigate the effect of physical exercise on ET plasma concentrations and the effect of α- and β-blockade on ET concentrations at rest and during exercise. Fifteen young volunteers (age 20–35 years) performed an exercise test on a bicycle ergometer. The starting workload of 50 W was increased by 30 W every 3 min until maximal heart rate was achieved; after a 2 min recovery period at 50 W the test continued for 15 min at 60% maximal work load. Blood samples were taken for ET determination before and after the test. After 1 week, the test was repeated. In the 2 days before either the first or the second test, each volunteer randomly received carvedilol (C) (25 mg), an α₁-adrenoceptor and β-adrenoceptor blocker. There was no significant difference in ET concentrations after exercise with or without C administration (1.24 ± 0.66, 1.42 ± 0.83, 1.66 ± 1.15, 1.61 ± 0.87 pg/mL), showing that prolonged aerobic exercise does not affect plasma ET levels. Moreover, in our healthy young volunteers, blockade of α- and β-adrenoceptors had no effect on ET levels at rest and after exercise.     

Adrenaline-induced "oxygen-wastage" and enzyme release from working rat heart. Effects of calcium antagonism, beta-blockade, nicotinic acid and coronary artery ligation

Adrenaline in a high dose (10⁻⁶m) caused the following harmful effects on mechanical and biochemical parameters of the isolated working rat heart: (i) loss of efficiency of mechanical work from 4.48 ± 0.20 to 3.24 ± 0.13 joules per ml O₂ (P < 0.001), so that much more oxygen was required to do the same amount of work (“oxygen-wastage”); (ii) a decreased cardiac output despite increased power production (from 14.2 ± 0.7 to 18.9 ± 0.8 mW/g, (P < 0.001); (iii) a marked release of lactate dehydrogenase (value 10 min after adrenaline: 558 ± 113 mU/g/min; vs control: 16 ± 2); and (iv) a decreased myocardial content of ATP. Interventions to counter the deleterious effects of adrenaline were: calcium antagonism, β-blockade, an antilipolytic agent, and a combination of calcium antagonism and an antilipolytic agent. From this, two separate aspects emerged. First, mechanical function as measured by cardiac output and power production was markedly improved by calcium antagonism which completely reversed the impairment of function caused by the high dose of adrenaline. β-blockade had also a less marked protective effect on mechanical function. Secondly, enzyme release was most effectively inhibited by the combination of calcium antagonism and inhibition of lipolysis or by propranolol. The inefficiency of work (“oxygen-wastage”) was β-mediated and Ca²⁺-dependent, whereas enzyme release was predominantly Ca²⁺-dependent and partially dependent on lipolysis. Hence the effects of β-blockade in inhibition of the adrenaline-provoked enzyme release could be ascribed to a combination of calcium-antagonism and inhibition of lipolysis.     

Adrenaline infusion in man increases muscle sympathetic nerve activity and noradrenaline overflow to plasma

This study was conducted to determine if muscle sympathetic nerve activity (MSA) and/or the neuronal release of noradrenaline per impulse are modulated by adrenaline in the physiological plasma concentration range. We gave step-wise infusions of adrenaline (0.05-0.6 nmol/kg per min) to 10 healthy young men and measured: intra-arterial blood pressure; heart rate; central venous pressure (CVP); efferent MSA (microneurography in the peroneal nerve); arterial (brachial artery) and femoral venous plasma concentrations of noradrenaline, and the spillover of noradrenaline to arterial and venous plasma (radiotracer infusion). The infusion of adrenaline caused a fall in diastolic blood pressure and tachycardia, and was associated with increases in MSA and noradrenaline spillover. These observations suggest that part of the adrenaline-induced increase in transmitter release is due to enhanced nerve impulse activity, but such a conclusion rests on the absence of diffusion limitations from the site of noradrenaline infusion into the blood stream. After termination of adrenaline infusion the tachycardia and elevated plasma noradrenaline levels persisted, but these changes were probably due mainly to a profound increase in nerve activity. Concurrently, there was a reduction in CVP which may have triggered the increase in efferent sympathetic nerve activity. Infusions of adrenaline did not influence the clearance of noradrenaline from arterial plasma, but the fractional extraction over the leg was moderately reduced, indicating that more arterial noradrenaline is recovered in venous plasma during adrenaline infusion. The present data suggest that the reasons for the adrenaline-induced increase in noradrenaline release are complex, but they are consistent with the hypothesis that stress levels of adrenaline enhance sympathetic nerve activity, and that circulating adrenaline may modulate both haemodynamic and neural responses to stress.     

Adrenocortical and adrenomedullary responses of fowl to treadmill exercise

Adrenomedullary and adrenocortical responses of 40-day-old cockerels to treadmill exercise (0.4 km/hr, 0 degrees incline) were determined. Plasma concentrations of adrenaline were increased above both resting and control levels (P less than 0.001) after 30 min exercise and continued to increase (P less than 0.01) until the cessation of exercise. Plasma noradrenaline and dopamine levels were increased after 60 min of exercise (P less than 0.01 and 0.05, respectively). The adrenaline component of the plasma catecholamine response increased significantly above that of noradrenaline (P less than 0.001). Plasma corticosterone levels were also increased (P less than 0.001) during exercise and were closely correlated with plasma adrenaline concentrations. Exercise depleted (P less than 0.01) adrenal stores of adrenaline, which were inversely proportional to plasma adrenaline concentrations (P less than 0.001). Neither adrenal noradrenaline nor dopamine were significantly correlated with their plasma levels. These results suggest that adrenocortical (corticosterone) and adrenomedullary (adrenaline) responses during exercise may occur in response to similar stimuli or may be interrelated.     

Plasma adrenaline and noradrenaline concentrations in diabetic patients with and without autonomic neuropathy at rest and during sympathetic stimulation

Summary Plasma concentrations of adrenaline and noradrenaline were measured radio-enzymatically in nine patients with diabetic autonomic neuropathy, seven diabetic patients without autonomic neuropathy and nine normal subjects, in the recumbent position and after standing. Furthermore, in six patients with autonomic neuropathy and in the normal subjects, plasma noradrenaline and adrenaline concentrations were determined during and after cyclo-ergometer exercise. No differences in plasma adrenaline concentrations were found at any time in the study. Basal plasma noradrenaline levels were significantly lower in diabetic patients with autonomic neuropathy than in the non-neuropathic diabetics or healthy control subjects. After standing, plasma noradrenaline rose to significantly higher levels in both control and diabetic subjects without neuropathy than in the patients with autonomic neuropathy. During exercise (up to 100 W load), plasma noradrenaline rose to similar levels in healthy controls and in patients with diabetic neuropathy. These data indicate that in diabetic autonomic neuropathy there is reduced peripheral neurosympathetic tone at rest but a normal response to moderate exercise. Blunted neurosympathetic responses to standing seem to be a consistent feature of diabetic autonomic neuropathy, particularly in those patients with severe postural hypotension.     

Aerobic exercise training increases circulating insulin-like growth factor binding protein-1 concentration, but does not attenuate the reduction in circulating insulin-like growth factor binding protein-1 after a high-fat meal

Insulin-like growth factor binding protein-1 (IGFBP-1) has metabolic effects throughout the body, and its expression is regulated in part by insulin. Circulating IGFBP-1 predicts development of cardiometabolic diseases in longitudinal studies, and low IGFBP-1 concentrations are associated with insulin resistance and consumption of a high-fat diet. Because of the favorable metabolic effects of regular aerobic exercise, we hypothesized that aerobic exercise training would increase plasma IGFBP-1 concentrations and attenuate the reduction in IGFBP-1 after a high-fat meal. Ten overweight (body mass index = 28.7 ± 0.9 kg/m(2)), older (61 ± 2 years) men and women underwent high-fat feeding and oral glucose tolerance tests at baseline and after 6 months of aerobic exercise training. In response to aerobic exercise training, subjects increased cardiorespiratory fitness by 13% (P < .05) and insulin sensitivity index by 28% (P < .05). Basal plasma concentrations of IGFBP-1 increased by 41% after aerobic exercise training (P < .05). The insulin response to an oral glucose tolerance test was a significant predictor of fasting plasma IGFBP-1 concentrations at baseline and after exercise training (P = .02). In response to the high-fat meal at baseline, plasma IGFBP-1 concentrations decreased by 58% (P < .001); a 61% decrease to similar postprandial concentrations was observed after exercise training (P < .001). Plasma insulin response to the high-fat meal was inversely associated with postprandial IGFBP-1 concentrations at baseline and after exercise training (P = .06 and P < .05, respectively). Although aerobic exercise training did not attenuate the response to a high-fat meal, the increase in IGFBP-1 concentrations after exercise training may be one mechanism by which exercise reduces risk for cardiometabolic diseases in older adults.     

Circulating catecholamine and potassium concentrations early in acute myocardial infarction: effect of intervention with timolol

In a prospective study, 20 patients with a first acute myocardial infarction and no current treatment with diuretics or cardioactive drugs were randomized to treatment with intravenous timolol (10 patients) or placebo (10 patients). Plasma adrenaline, noradrenaline, and serum potassium were estimated at baseline (mean +/- SD 3.6 +/- 0.8 hours after the onset of the infarction) and 4 hours after the start of treatment. The patient selection criteria embraced a low-risk study population. Before treatment, the serum potassium concentrations correlated inversely with plasma adrenaline but not with plasma noradrenaline concentrations. A rise of serum potassium (mean +/- SD mmol/L) from 4.1 +/- 0.3 to 4.4 +/- 0.4 (p less than 0.05) in the placebo group and from 4.0 +/- 0.4 to 4.5 +/- 0.5 (p less than 0.05) in the timolol group was in multivariate analysis associated with infarct size, estimated as cumulative creatine kinase release, in the placebo group, and with the mean individual plasma adrenaline concentrations in the timolol group. By reversing the effect of adrenaline from a decrease to an increase in the serum potassium concentrations, timolol changes the relationships between circulating adrenaline, potassium, and infarct size.     

Effect of beta-blockade and subsequent triiodothyronine administration on human leucocyte Na-K ATPase

We have investigated the effect of beta-blockade and beta-blockade + triiodothyronine (T3) administration on 86Rb (K) influx and [3H]-ouabain binding by human leucocytes and on plasma potassium concentrations. beta-blockade with nadolol (40 mg daily) for five days resulted in a significant decrease in 86Rb influx and [3H]-ouabain binding, as well as an increase in plasma potassium concentration. T3 administration thereafter caused a fall in plasma concentration and an increase in 86Rb influx. There was a tendency toward restoration of [3H]-ouabain binding to normal. The fact that beta-blockade inhibits 86Rb (K) influx and increases plasma potassium concentration implies that endogenous adrenaline exerts a tonic stimulatory effect upon 86Rb (K) influx and a suppressive effect on plasma potassium concentrations in vivo. T3 administration induces an increase in 86Rb (K) influx and a fall in plasma potassium concentrations. This suggests that either the effect of T3 is independent of beta-adrenoceptors or that the known increase in beta-adrenoceptor population secondary to T3 administration increases sensitivity to circulating adrenaline in spite of beta-blocker administration.     

Metabolic, hemodynamic, and electrocardiographic responses to increased circulating adrenaline: effects of pretreatment with class 1 antiarrhythmics.

In order to study the effects of treatment with class 1 antiarrhythmics on the metabolic, hemodynamic, and electrocardiographic responses to adrenaline, 12 healthy volunteers were infused on four occasions, after pretreatment with placebo, disopyramide, mexiletine, and flecainide, respectively, with adrenaline at a rate producing serum adrenaline concentrations comparable with those seen in acute myocardial infarction. After pretreatment with placebo adrenaline caused significant falls in serum potassium, serum magnesium, serum calcium, and serum phosphate and a significant increase in blood glucose. Adrenaline also caused a significant increase in heart rate and systolic blood pressure and a significant fall in diastolic blood pressure. On the electrocardiogram a significant prolongation of QTc duration and a flattening of the T-wave amplitude were seen. Pretreatment with disopyramide had no effect on the hemodynamic response to adrenaline but caused a significant prolongation of Qtc duration before the adrenaline infusion. Pretreatment with mexiletine was associated with a significantly greater fall in serum potassium during adrenaline infusion, and pretreatment with flecainide with a greater fall in serum magnesium, as compared with placebo pretreatment Flecainide also caused a significant prolongation of the QRS duration before adrenalin infusion, and after all the active pretreatments a prolongation of QRS duration was seen during adrenaline infusion. The metabolic and hemodynamic changes during adrenaline infusion may not only reduce the antiarrhythmic efficacy of antiarrhythmics but may also increase the risk of proarrhythmic effects in a clinical setting. These results may help to explain why treatment with antiarrhythmics seems to be without beneficial effect on mortality in post-myocardial infarction patients.     

Platelet factor 4 release during exercise in patients with coronary artery disease

Many recent studies provide evidence that increased platelet activation occurs in a significant number of patients with atherosclerotic coronary artery disease. The mechanisms responsible for this activation are unknown, although there have been studies suggesting a correlation with abnormal lipoproteinemia, acute myocardial infarction, unstable angina, and exercise-induced myocardial ischemia. We studied 84 patients undergoing standardized treadmill exercise using either a Bruce [N = 63] or symptom-limited Naughton protocol [N = 21]. In contrast to ten healthy volunteer subjects, the patient group demonstrated a significant increase in plasma concentrations of platelet factor 4 [PF4] between pre- and postexercise blood samples confirming earlier reports of exercise-induced platelet activation and secretion. As with previous studies, however, only a subset of patients demonstrated this response. When the entire group was analyzed for the presence or absence of electrocardiographic ischemic changes and the presence of documented versus suspected coronary artery occlusions, there were no differences noted between groups that explained the variable responses measured. However, there was a significant difference between patient groups when analyzed by whether or not they were being treated with β-blocking agents. Patients who were being treated with propranolol or one of the longer-acting β-blocking agents did not have a significant increase in plasma PF4 following exercise, in contrast to patients who were not β-blocked. Plasma concentrations of epinephrine, norepinephrine, and lactic acid were measured in 49 patients and all normal subjects. There was no correlation between the changes in plasma PF4 concentrations and any of these three variables, suggesting that platelet activation was not occurring through direct platelet activation by circulating catecholamines. This study provides further evidence that there is a subset of CAD patients with platelet hyperactivity. This is the first time that β-blockade has been demonstrated to modify this platelet response. The effectiveness of β-blocking agents in CAD may be in part related to their antiplatelet effect.     

CARDIOVASCULAR RESPONSES IN HYPERTHYROIDISM BEFORE AND DURING 0-ADRENOCEPTOR BLOCKADE: EVIDENCE AGAINST ADRENERGIC HYPERSENSITIVITY

The relationship between the sympathetic nervous system and cardiovascular responses has been studied indirectly in ten hyperthyroid patients and age matched euthyroid controls. Nyctohemeral variations in heart rate, and heart rate and blood pressure responses to exercise were measured before and during β-blockade with slow-release propranolol. Both groups showed a parallel variation in heart rate over 24 h, with an increase in heart rate in the hyperthyroid group that was the same during the day (27·9 ± 0·95 beats/min) and during the night (26·7 ± 0·75 beats/min). Similarly, the increase in resting heart rate (32·7 ± 4·4 beats/min) in the hyperthyroid group was close to the increase in peak exercise-induced heart rate (25·0 ± 4·7 beats/min). Adequate β-blockade was achieved in all subjects as evidenced by a percentage reduction in peak exercise heart rate of 25–45%. Propranolol caused a greater reduction in daytime than night-time heart rate in both groups and blunted the response to exercise. Following β-3-blockade, the mean percentage reduction in heart rate and systolic blood pressure during exercise, and heart rate responses over 24 h were similar in hyperthyroid and euthyroid groups. The closest correlation between thyroid hormone levels and heart rate was that of serum total tri-iodothyronine (T3) and nocturnal heart rate during β-bockade (r = 0.92; P < 0·001). It is concluded that excess circulating thyroid hormones exert a direct effect on the cardiovascular system additive to the sympathetic nervous system and that there is no evidence of adrenergic hypersensitivity in hyperthyroidism.     

Effect of adrenaline on basal and ovine corticotrophin-releasing factor-stimulated ACTH secretion in man

Six normal male subjects were given, in single blind random order on six separate occasions, i.v. bolus doses of synthetic ovine corticotrophin-releasing factor-41 (oCRF-41; 25 and 50 micrograms) with and without adrenaline (3 micrograms/min) i.v. for 150 min, the adrenaline infusions alone and saline placebo. The adrenaline infusions resulted in plasma adrenaline concentrations of 4.33 +/- 0.82 (S.E.M.) nmol/l and were associated with an increase in blood glucose, heart rate and systolic blood pressure and a reduction of diastolic blood pressure. Despite these evident biological effects at several sites, there was no stimulation of plasma ACTH or cortisol by adrenaline in comparison with the effect of saline, and no enhancement of the stimulatory effect of either dose of oCRF-41 on ACTH or cortisol secretion. The ACTH response to 50 micrograms oCRF-41 was greater than that to 25 micrograms, indicating that the 25 micrograms dose of oCRF-41 was submaximal and capable of further enhancement. As the plasma adrenaline concentrations during the adrenaline infusions reached the upper limit of the physiological range of plasma adrenaline in man, yet failed to enhance the ACTH or cortisol responses to a submaximal dose of oCRF-41, we conclude that circulating adrenaline neither exerts a direct stimulatory effect on pituitary corticotrophs nor enhances the effect of CRF under physiological circumstances. The adrenaline infusions attenuated the ACTH and cortisol responses to oCRF-41 and were associated with a transient reduction of basal concentrations of both hormones.     

Effects of adrenergic and muscarinic receptor stimulation on serum potassium concentrations and myocardial electrical stability

The influence of adrenergic and muscarinic receptor activation on cardiac electrical stability and on serum potassium concentrations was studied in 23 anaesthetised dogs. The ventricular fibrillation threshold was assessed using the single stimulus technique. Adrenaline (1.0 microgram X kg-1 X min-1) caused a brief rise and a subsequent prolonged fall in serum potassium concentration, which was accompanied by a decline in ventricular fibrillation threshold when baroreceptor activation was prevented. After pretreatment with the beta1 adrenoceptor blocking agent metoprolol (0.5 mg X kg-1), adrenaline did not alter vulnerability to ventricular fibrillation but still elicited hypokalaemia. In contrast, selective beta2 adrenoceptor blockade (ICI 118551, 100 micrograms X kg-1) prevented the adrenaline induced lowering of serum potassium concentration but not of ventricular vulnerability. Muscarinic receptor activation by methacholine (3.0 micrograms X kg-1 X min-1) had no effect on serum potassium concentration but increased the ventricular fibrillation threshold by 30%. When methacholine was administered concomitantly with adrenaline the decline in serum potassium concentration persisted, but the increase in ventricular vulnerability was completely prevented. It is concluded that in the normal canine myocardium adrenaline produces an increase in vulnerability that is mediated through beta 1 adrenoceptors and that the beta 2 adrenoceptor mediated hypokalaemia is dissociated from electrophysiological effects of adrenaline. Parasympathetic nervous system activation does not influence serum potassium concentrations but opposes the effects of adrenaline on susceptibility to ventricular fibrillation.     

Exercise Test in Patients with Sarcoidosis

ABSTRACT The study population comprises 28 patients with sarcoidosis who all had repolarization disturbances in their exercise ECGs. None of the patients had hypertension or known cardiovascular disease, and all but two were non-smokers. The mean age was 45 years. Exercise test with β-adrenergic blockade was performed within one month of the first examination. Persisting abnormal ST-T changes in exercise ECGs after β-blockade were seen in 12 (43%) patients. No significant relationship was found between persisting ST-T changes and age, sex, chest X-ray stage, lung function or working capacity. In an earlier study, we found ST-T abnormalities in exercise ECG in 56 of 127 individuals (44%) in a consecutive 5-year study of patients with newly detected sarcoidosis. From this and the present report we postulate that, in our region, as much as 20% of the patients with newly detected sarcoidosis might have organic myocardial disease, possibly of sarcoid origin, as shown by repolarization disturbances in exercise ECG. If ECG abnormalities in the ST-T region are present in patients with sarcoidosis, exercise ECG with β-blockade is a simple way of establishing suspicion of organic myocardial lesions. If exercise ECG abnormalities in the ST-T region persist after β-blockade, careful clinical follow-up is recommended, and, in some patients early steroid therapy should be considered.     

Physical Exercise after Alcohol Intake: Effect on Plasma Catecholamines and Lymphocytic β-Adrenergic Receptors

The combined effects of alcohol intoxication and intense physical exercise on the adrenergic system were studied in eight healthy male volunteers. Ethanol (0.8 g/kg body weight) was administered perorally to bring about a mean serum concentration of 21 mmol/liter (0.1%); each subject also participated in an identical control session without alcohol. Acute alcohol intake alone did not change the concentrations of plasma adrenaline or noradrenaline or the density, affinity, and functioning (ability to mediate catecholamine-stimulated production of cAMP) of lymphocytic beta-adrenergic receptors. In contrast, acute ergometer exercise brought about an approximately 10-fold increase of plasma adrenaline and noradrenaline concentrations, a 2- to 3-fold increase of beta-adrenergic receptor density and an enhancement of isoproterenol-stimulated cAMP production. Alcohol intake immediately before the ergometer exercise did not modify these changes. In conclusion, acute physical exercise activates the human adrenergic system, with an increase of both plasma catecholamines and lymphocytic beta-adrenergic receptors. Moderate alcohol intoxication does not affect exercise-induced alterations of these parameters.