Intravenous Infusion Of Isoprenaline Research Articles

P454 ARRHYTHMIC RISK AND REPOLARIZATION ALTERATIONS ON THE ECG UNCOVERED BY AN ISOPRENALINE TEST

Abstract A 62–year–old man came to our attention for a syncopal episode that occurred during a competitive race, without prodromes, lasting a few seconds, with total, spontaneous regression and without issues. On ECG sinus bradycardia, HR 46/min and QRS fragmented in V1. During monitoring were documented many polymorphic premature ventricular complex (PVC) and polymorphic nonsustained ventricular tachycardia (NSVT). Coronary angiography showed normal coronary arteries. The Isoprenaline test was performed (intravenous infusion of Isoprenaline 0.2 mg in 100 ml of physiological solution at variable speed until obtaining a HR increase of at least 20% compared to baseline). As HR increased, a clear epsilon wave in V1 became evident. Also documented numerous polymorphic PVC and polymorphic NSVT. Cardiac magnetic resonance (MRI) was performed with documentation of findings suggestive of primary cardiomyopathy with biventricular phenotypic expression with a clear left prevalence. All these elements placed the patient at high arrhythmic risk. An implantable cardiac defibrillator was then performed. The isoprenaline–induced increase in heart rate made the epsilon wave manifest, which is an expression of an extremely delayed depolarization caused by the fibroadipose replacement of portions of the myocardium (as documented by cardiac MRI). It was also possible to exclude a J–wave syndrome in which the alterations are of repolarization and are due to the epi–endocardial electrical gradient which increases and becomes more evident at lower heart rates. The test with isoprenaline has therefore allowed us to distinguish depolarization disorders from repolarization disorders and to direct us towards the former.

P13 COMPLETE ATRIOVENTRICULAR BLOCK IN A 52–YEAR–OLD MAN ASSOCIATED WITH LYMPHATIC CANCER WITH CARDIAC INVOLVEMENT

Abstract A 52–year–old man arrived at the local emergency room for worsening dyspnea and asthenia, present for about a month, but significantly worsening during the night of the access. The ECG (Figure 1) revealed complete AtrioVentricular Block (ABV) with a narrow–QRS junctional escape rhythm, with a heart rate of about 30 beats per minute (bpm). The other vital parameters were within the normal limits and no anomalies were detected on the physical examination. Medium–dose intravenous isoprenaline infusion was immediately started, with an increase in the junctional escape rate up to 50 bpm. The patient also underwent chest x–ray, which showed interstitial thickening in the pulmonary hilus, which was judged to be nonspecific. The blood chemistry was normal and the echocardiogram (Figure 2) did not show any abnormalities. Since there were no apparent reversible causes of the complete AV block, on the next day, a bicameral pacemaker was implanted via the left cephalic vein. The procedure was uneventful and the patient was discharged home two days later, in good general condition. Eight days after the discharge, surgical wound control and pacemaker control were performed, with completely normal parameters. About 15 days after the discharge the patient went back to the local emergency room for dyspnea and fever. Chest Computed Tomography (CT) without contrast medium was performed, which revealed the presence of widespread pathological mediastinal lymphadenopathy. Therefore, the patient was admitted to the internal medicine ward. An in–depth diagnostic was performed first with thoraco–abdominal angio–CT, then with Positron Emission Tomography (PET)–CT (see Figure 3), which revealed the presence of diffuse areas of fixation of the radio–drug (18F–Fluorodeoxyglucose –FDG–), at the ilo–mediastinal, hepatic, pulmonary, retrocrural, retrocaval, iliac, supra and subclavicular, and also cardiac area (activation of interatrial brown fat and between aortic root and the superior vena cava). The patient was therefore transferred to another hospital for diagnostic investigations and lymphoma therapy. In the light of the picture that emerged, the arrhythmological disease was considered to be referred to the cardiac involvement of the oncological disease; to date there are few similar cases described in the literature. Legend of the figures: Figure 1: ECG at the admission Figura 2: Echocardiogram at the admission Figura 3: PET / CT with myocardial areas of 18F–FDG fixation.

Idiopathic accelerated idioventricular rhythm or ventricular tachycardia originating from the right bundle branch: unusual type of ventricular arrhythmia.

Accelerated idioventricular rhythm (AIVR) or ventricular tachycardia (VT) originating from the right bundle branch (RBB) is rare and published clinical data on such arrhythmia are scarce. In this study, we will describe the clinical manifestations, diagnosis, and management of a cohort of patients with this novel arrhythmia. Eight patients (5 men; median age, 25 years) with RBB-AIVR/VT were consecutively enrolled in the study. Pharmacological testing, exercise treadmill testing, electrophysiological study, and catheter ablation were performed in the study patients, and ECG features were characterized. All RBB-AIVR/VTs were of typical left bundle-branch block morphology with atrioventricular dissociation. The arrhythmias, which demonstrated chronotropic variability, were often isorhythmic with sinus rhythm and were accelerated by physical exercise, stress, and intravenous isoprenaline infusion. The rate of RBB-AIVR/VT varied from 45 to 200 beats per minute. Two patients experienced syncope, and 3 had impaired left ventricular function. Metoprolol was proven to be the most effective drug to decelerate the arrhythmia rate and relieve symptoms. Electrophysiology study was performed in 5 patients and the earliest activation with a sharp RBB potential was localized in the mid or distal RBB area. Catheter ablation terminated the arrhythmia with subsequent RBB block morphology during sinus rhythm. During follow-up, patients' symptoms were controlled with normalization of left ventricular function either on metoprolol or by catheter ablation. RBB-AIVR/VT is an unusual type of ventricular arrhythmia. It can result in significant symptoms and depressed ventricular function and can be successfully treated with catheter ablation.

Yellow oleander poisoning in eastern province: An analysis of admission and outcome

Cardiac toxicity after self-poisoning from ingestion of yellow oleander seeds is common in Eastern Sri Lanka. To determine the clinical manifestations, cardiac arrhythmias, electrolytes abnormalities and outcome of management using currently available treatment, Poisoning Unit, Tertiary Care Hospital in Eastern Sri Lanka. We studied 65 patients [Mean age : 23(± 0.43)yrs], (Male: Female=27:38) with yellow oleander poisoning (YOP) admitted to a Poisoning Unit, Tertiary Care Hospital in Eastern Sri Lanka from January to December 2011. Most patients are symptomatic who presented with classical symptoms of vomiting, abdominal pain and diarrhea. Cardiac dysrhythmias such as bradycardia or an irregular pulse are the most common findings on examination. Most symptomatic patients had conduction defects affecting the sinus node, the atrioventricular (AV) node, or both. Patients showing cardiac arrhythmias that required transfer for specialised management had significantly higher serum potassium concentrations. Almost all patients were treated with multiple activated charcoal even late presentation. Patients with brad arrhythmias were treated with intravenous boluses of atropine and intravenous infusions of isoprenaline. Temporary cardiac pacing was done for those not responding to drug therapy. There were two deaths (3.07%), both had third-degree heart block. They died even definitive treatment could be instituted. Of the remaining 63 patients, 54 (83.1%) patients required treatment, and 29 were treated with only atropine and/or isoprenaline while one required cardiac pacing in addition. 12 (18.4%) patients had arrhythmias that were considered life threatening (second-degree heart block type II, third-degree heart block and nodal bradycardia). They had good recovery even though they had developed cardiac toxicity. YOP are common among young females. The cardiac toxicity develops within 24 hrs of ingestion of YO seeds. The risk of toxicity has negative correlation with number of seeds. Most patients have nonspecific symptoms. AV conduction defects are common. Multiple activated charcoals alone were safe and adequate in most cases even late presentation.

Myocardial necroses produced by intravenous infusion of isoprenaline into rats.

Abstract Intravenous infusion of isoprenaline in doses of 2,20,200,2000 μg/kg per min over 20 min into heparinized Wistar rats results in myocardial necroses and a rise in SGPT activity, erythrocyte sedimentation rate and leucocytosis. A quantitative method for estimation of intensity and distribution of myocardial necrotic foci is described. The intensity of myocardial lesions is observed linearly related to the infused isoprenaline at 2, 20 and 200 μg/kg per min. Damaged areas are mainly found in subendocardial and apical regions of left ventricle.

Short‐term β‐adrenergic regulation of leptin, adiponectin and interleukin‐6 secretion in vivo in lean and obese subjects

Adipose tissue and skeletal muscle are endocrine organs, secreting substances that have been implicated in obesity-related disorders. This study examined short-term beta-adrenergic regulation of circulating leptin, adiponectin and interleukin-6 (IL-6) concentrations and secretion from abdominal subcutaneous adipose tissue and muscle (IL-6) in vivo in lean and obese subjects. Systemic concentrations and net fluxes of leptin, adiponectin and IL-6 across abdominal subcutaneous adipose tissue and forearm skeletal muscle (IL-6) were assessed before and during beta-adrenergic stimulation (intravenous isoprenaline infusion) in 13 lean and 10 obese men. Basal circulating leptin concentrations were higher in the obese (p < 0.001), while circulating adiponectin (p = 0.45) and IL-6 concentrations (p = 0.41) were not different between groups. beta-Adrenergic stimulation decreased leptin concentrations in both groups (p < 0.01), but did not reduce net abdominal subcutaneous adipose tissue leptin release. Increased leptin clearance and/or decreased leptin secretion from other fat depots may explain the reduction in leptin concentrations. Adiponectin concentrations remained unchanged during beta-adrenergic stimulation in both groups. beta-Adrenergic stimulation increased IL-6 concentration, which was more pronounced in the obese (p = 0.01 vs. lean). This cannot be explained by increased IL-6 release per unit abdominal subcutaneous adipose tissue and muscle but might be because of the increased fat mass and fat-free mass at whole-body level. Short-term beta-adrenergic stimulation decreases leptin concentrations, which cannot be explained by reduced net leptin release from abdominal subcutaneous adipose tissue, while it elevates IL-6 concentration partly by increased release from this fat depot and muscle. Finally, beta-adrenergic stimulation has no short-term regulatory role in adiponectin secretion.

Acute regulation of plasma leptin by isoprenaline in lean and obese fasted subjects

In human obesity, there is some evidence for impaired adrenergic sensitivity with respect to catecholamine-induced lipolysis. The beta-adrenoceptor agonist isoprenaline has been shown to suppress plasma leptin levels in lean humans in vivo. We hypothesized that a reduced adrenergic sensitivity in obese humans would result in impaired suppression of leptin secretion. Eight obese [Ob, body mass index (BMI) = 33.3 kg/m2] and seven lean (Ln, BMI = 21.8 kg/m2) men were studied after an overnight fast. Intravenous isoprenaline infusion was initiated at a rate of 8 ng/kg/min, titrated up to 24 ng/kg/min over 30 min and continued at this rate for a further 120 min with continuous electrocardiogram monitoring. Baseline fasting plasma leptin was higher in obese compared with lean subjects (Ob 12.2 +/- 1.8, Ln 2.6 +/- 0.6 ng/ml, p < 0.05 unpaired t-test). Baseline fasting glycerol as a measure of lipolysis was similar in both groups (Ob 62.9 +/- 7.6, Ln 42.4 +/- 8.9 micromol/l) and increased from baseline to 150 min by equivalent amounts (Ob +66.9%, Ln +81.2%, p = NS). Plasma leptin decreased from baseline to 150 min with similar relative changes in both groups (Ob -29.2%, Ln -27.8%). Obese subjects show a similar lipolytic and leptin response to acute isoprenaline infusion compared with lean subjects. Impaired beta-adrenergic-induced inhibition of leptin secretion does not appear to contribute to hyperleptinaemia in obese human subjects.

Catheter ablation of junctional ectopic tachycardia in children, with preservation of atrioventricular conduction

Idiopathic junctional ectopic tachycardia is a rare arrhythmia in children. Several studies have demonstrated that drug therapy is often ineffective and sometimes the only achieved effect is rate control. Early presentation and frequent recurrence are associated with adverse outcome. Three consecutive children, aged 9, 7 and 12 years respectively, underwent radiofrequency catheter ablation for junctional ectopic tachycardia, after having failed antiarrhythmic drug therapy. The entire His bundle was plotted out and marked, using the Localisa navigation system. The arrhythmia was readily and repeatedly inducible using intravenous isoprenaline infusion and the site of earliest retrograde conduction during tachycardia could be assessed. Ablations were performed in sinus rhythm, empirically targeting the site of earliest retrograde conduction during tachycardia. This approach was successful in abolishing tachyarrhythmia in the first two patients, in whom the successful ablation site was located superoparaseptally. In the third patient, junctional ectopic tachycardia was inducible, despite abolishing retrograde atrial activation, in a septal location on the tricuspid valve annulus. Further ablations in the superoparaseptal region, closer to the His bundle, were successful in rendering tachyarrhythmia noninducible. Over a median follow-up of 10 months, none of the patients has had recurrence of arrhythmia, despite discontinuing all antiarrhythmic medications. Radio frequency catheter ablation of junctional ectopic tachycardia is feasible with preservation of atrioventricular conduction.

Torsade De Pointes Caused By Concomitant Use Of Ketoconazole And Terfenadine

A 47-year-old female developed frequent syncope eight days after the administration of oral ketoconazole and terfenadine for fungal infection and urticaria respectively. ECG at hospital admission showed prolonged QT interval and TDP. The patient had no previous history of syncope nor did she have other risk factors for TDP. Both ketoconazole and terfenadine were immediately discontinued, followed by intravenous infusion of isoprenaline (2.0 μg/min) to maintain the heart rate at 100 beats/min. TDP resolved after the management. QT interval returned to normal range within 5 days of admission. She had no recurrence in TDP or QT prolongation during the follow up of six months. Conclusions: Terfenadine prolongs QT interval and leads to lifethreatening ventricular arrhythmia. This cardiac toxicity may be enhanced by concomitant use of liver enzyme inhibitor ketoconazole.

Yellow oleander poisoning in Sri Lanka: outcome in a secondary care hospital.

Cardiac toxicity after self-poisoning from ingestion of yellow oleander seeds is common in Sri Lanka. We studied all patients with yellow oleander poisoning (YOP) admitted to a secondary care hospital in north central Sri Lanka from May to August 1999, with the objective of determining the outcome of management using currently available treatment. Patients with bradyarrhythmias were treated with intravenous boluses of atropine and intravenous infusions of isoprenaline. Temporary cardiac pacing was done for those not responding to drug therapy. During the study period 168 patients with YOP were admitted to the hospital (male:female = 55:113). There were six deaths (2.4%), four had third-degree heart block and two died of undetermined causes. They died soon after delayed admission to the hospital before any definitive treatment could be instituted. Of the remaining 162 patients, 90 (55.6%) patients required treatment, and 80 were treated with only atropine and/or isoprenaline while 10 required cardiac pacing in addition. Twenty-five (14.8%) patients had arrhythmias that were considered life threatening (second-degree heart block type II, third-degree heart block and nodal bradycardia). All patients who were treated made a complete recovery. Only a small proportion of patients (17%) admitted with YOP developed life-threatening cardiac arrhythmias. Treatment with atropine and isoprenaline was safe and adequate in most cases.

Endurance training increases the beta-adrenergic lipolytic response in subcutaneous adipose tissue in obese subjects.

The aim of this study was to assess, by longitudinal follow-up, the influence of aerobic training on the in vivo lipolytic activity of adipose tissue in obese male subjects. Eleven obese non-diabetic males, aged 41.5+/-5.77 (range 27-49 y) with body mass index (BMI) 36.5+/-4.5 kg/m2 (range 29.4-47.1 kg/m2) participated in the study. Subjects took part in a 12-week aerobic training program. Before and after training, microdialysis of abdominal subcutaneous adipose tissue (SCAT) was carried out, using perfusion with graded doses of the beta-adrenergic agonist isoprenaline and a single dose of the phosphodiesterase inhibitor theophylline. In addition, the response of plasma glycerol and free fatty acids (FFAs) to intravenous infusion of graded doses of isoprenaline was tested. The training did not induce significant weight loss and promoted an increase in maximum aerobic capacity (P<0.05). The increase of extracellular glycerol in SCAT in response to isoprenaline perfusion was enhanced after the training (P<0.05), while no change in the response of interstitial glycerol to theophylline action was observed. The training did not elicit a change in the isoprenaline-induced changes of blood flow in adipose tissue. The increases of plasma FFAs and glycerol in response to intravenous isoprenaline infusion, were significantly enhanced after training. The present study shows that aerobic training induced an increase in the response of plasma and subcutaneous adipose tissue concentration of glycerol to beta-adrenergic stimulation. The effect of an agent acting at the post-receptor level (theophylline) in SCAT was not modified by training.

Effect of isoprenaline on plasma leptin and lipolysis in humans

The sympathetic nervous system may play a central role in the regulation of both lipolysis and leptin production. Therefore, we investigated the effect of intravenous infusions of the beta-adrenergic agonist isoprenaline on plasma concentrations of leptin and nonesterified fatty acids. Eight lean, healthy human volunteers, (4M:4F; median (interquartile range) age 36.5 (30.8-40.0) years; BMI 22.9 (20.1-29.2) kg.m-2; % body fat 24.5 (17.9-26.3)), were studied following an overnight fast. Intravenous infusion of isoprenaline was carried out for 3 h, followed by a 1 hour recovery phase. The isoprenaline infusion rates (0.5-3.5 micrograms.min-1) were titrated individually for each subject in order to achieve similar biological sympathetic responses based on heart rate (target heart rates were > 100 min-1 but < twice resting heart rate). Plasma leptin was determined using an in-house radioimmunoassay, nonesterified fatty acids estimated with an enzymatic colourimetric assay and insulin concentrations were assayed using a specific, two-site immunoenzymometric assay. Fasting preinfusion plasma leptin concentrations (6.3 (3.0-12.8) micrograms/l) correlated with percentage body fat measured by bioimpedance (r = 0.95; P < 0.001). Plasma leptin concentrations were rapidly suppressed by isoprenaline, with maximal suppression (20.5 (15.0-25.0)% of preinfusion levels (Wilcoxon rank sum test; P < 0.05)), observed after 2 h. In the recovery period, plasma leptin concentrations rapidly returned to preinfusion levels (postinfusion vs maximally suppressed leptin concentrations P < 0.05; vs preinfusion leptin concentrations P = NS). Plasma nonesterified fatty acids and insulin concentrations showed opposite changes to those observed with leptin. Plasma leptin concentrations are rapidly and reversibly suppressed by the infusion of isoprenaline in humans in vivo.

Comparison of some properties of pronethalol and propranolol. 1965.

Comparison of some properties of pronethalol and propranolol. 1965.

Effects of chronic intravenous infusions of dopexamine and isoprenaline to rats on D1‐, β1‐ and β2‐receptor‐mediated responses

1. Rats received intravenous infusions of dopexamine, an agonist with selectivity for D1-dopamine receptors and beta 2-adrenoceptors (240 micrograms kg-1 h-1), isoprenaline, a beta 1- and beta 2-adrenoceptor agonist (40 micrograms kg-1 h-1) or vehicle (isotonic saline at pH 2.5) for 7 days via subcutaneously implanted osmotic minipumps. Tissues were then removed for determination of functional responsiveness to beta 1-adrenoceptor, beta 2-adrenoceptor and dopamine D1-receptor stimulation. 2. The beta 1-adrenoceptor-mediated responses of the spontaneously beating right atrium (increase in rate) and paced left atrium (increase in tension) showed significant reductions in sensitivity to isoprenaline following isoprenaline infusion. The EC50 values were significantly increased from 5.6 to 17.7 nM in right atria and from 7.4 to 27.1 nM in left atria. The maximum rate increase of right atria was also significantly less after isoprenaline infusion compared with controls (164.0 and 251.9 beats min-1, respectively) but the maximum tension responses of left atria were not significantly different. After infusion with dopexamine, however, there was no change in sensitivity of the left or right atria to beta 1-adrenoceptor stimulation by isoprenaline. 3. beta 2-Adrenoceptor-mediated relaxation responses to isoprenaline of the pulmonary artery, constricted with noradrenaline (6 x 10(-8) M), showed no significant difference in maximum response or EC50 in tissue from isoprenaline- or dopexamine-infused rats compared with vehicle-infused controls. beta 2-Adrenoceptor-mediated vasodilator responses were also examined in the kidney perfused with the thromboxane A2 analogue, U46619 (7.1 x 10(-8) M) to raise perfusion pressure. As with the pulmonary artery, there was no significant difference in ED50 or maximum response to isoprenaline in kidneys from isoprenaline infused animals compared with vehicle controls.4. The DI-receptor-mediated vasodilator responses to dopamine of the kidney perfused with U46619were reduced after infusion of rats with dopexamine. The maximum fall in perfusion pressure(16.0 mmHg) and ED50 value (5.2 microg) were significantly different from those after vehicle infusion(31.5 mmHg; 1.5 microg).5. These results show that functional responses mediated via beta1-adrenoceptors and DI-receptors are reduced by intravenous infusions of isoprenaline and dopexamine, respectively. In contrast, the beta2-adrenoceptor-mediated vasodilator responses of the pulmonary artery and kidney are not reduced by these agonists. Thus, under identical conditions, there appears to be selective down-regulation of peripheral beta 1- and D,-receptors, but not of beta 2-adrenoceptors.

Parallel increases in noradrenaline reuptake and release into plasma during activation of the sympathetic nervous system in rabbits

Rates of noradrenaline reuptake and spillover into plasma were examined in conscious rabbits before and during activation of the sympathetic nervous system to determine whether neuronal reuptake varies disproportionately or in parallel with increases in noradrenaline release. The sympathetic nervous system was stimulated by nitroprusside-induced hypotension, 2-deoxyglucose-induced glucopenia or intravenous infusion of isoprenaline before and after administration of desipramine to block neuronal uptake. Spillover of noradrenaline into plasma was estimated from the dilution of intravenously infused 3H-noradrenaline with endogenous plasma noradrenaline. The amount of dihydroxyphenylglycol (DHPG) in plasma that was derived from metabolism of recaptured noradrenaline, together with the desipramine-induced decreases in clearance from plasma of 3H-noradrenaline and appearance in plasma of 3H-DHPG, were used to estimate the rate of neuronal reuptake of noradrenaline. The mean (+/- SEM) resting noradrenaline reuptake rate (n = 28) was 0.62 +/- 0.04 nmol kg-1 min-1, 5-fold greater than the rate of its spillover into plasma (0.12 +/- 0.02 nmol kg-1 min-1). Intravenous infusion of nitroprusside at 3 rates titrated to cause graded increases in heart rate caused 74%, 129% and 240% increases in noradrenaline spillover into plasma and 66%, 104% and 198% increases in noradrenaline reuptake. At 15-30 min after intravenous injection of 2-deoxyglucose (500 mg/kg) there was a 106% increase in noradrenaline spillover and a 93% increase in noradrenaline reuptake. Infusion of isoprenaline (0.25 micrograms kg-1 min-1) caused a 102% increase in noradrenaline spillover and a 130% increase in noradrenaline reuptake.(ABSTRACT TRUNCATED AT 250 WORDS)

β-adrenergic responsiveness in stress-sensitive and stress-resistant pigs

This study investigated whether enhanced metabolic responsiveness to beta-adrenergic stimulation might explain the liability of the stress-sensitive pig to develop an acidosis during stressful situations. Blood lactate, pH, PCO2 and heart rate response to an intravenous infusion of isoprenaline were examined in three lines of pentobarbitone anaesthetized, atropinized pigs. The lines were Pietrain X Hampshire which had been selected over eight generations for a positive reaction to the halothane test (stress-sensitive); Pietrain X Hampshire which had been selected over eight generations for no reaction to the halothane test (stress-resistant) and British Landrace which had been selected over four generations for a positive halothane reaction (stress-sensitive). The metabolic responses to isoprenaline were greater in the stress-sensitive Pietrain X Hampshire line than the stress-resistant line. The stress-sensitive Landrace pigs, however, had smaller changes in pH and PCO2 in response to isoprenaline than the stress-resistant Pietrain X Hampshire pigs. This inconsistent trend across the three lines led to the conclusion that enhanced beta-adrenergic responsiveness was not the likely cause of stress sensitivity.

Spermidine/spermine-N1-acetyltransferase activity in isoprenaline-stimulated rat salivary glands.

In parotid, sublingual and submaxillary glands stimulated by continuous intravenous infusion of isoprenaline at various doses for 3 h, the concentrations of the polyamines putrescine, spermidine, spermine and N1-acetylspermidine as well as the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase were determined. Ornithine decarboxylase is the enzyme that catalyses the formation of putrescine from ornithine. The most striking effect was observed in parotid glands. Here, the beta-adrenergic agonist increased the activity of spermidine/spermine-N1-acetyltransferase markedly, but only slightly (if at all) that of ornithine decarboxylase. It also increased the concentrations of N1-acetylspermidine and putrescine markedly. The result obtained in this gland indicates interconversion of higher polyamines to putrescine.

Inhibitory effect of isoprenaline on gastric acid secretion in the rat. The role of endogenous histamine

In dogs beta-adrenoreceptor agonists inhibit gastric acid secretion stimulated by exogenous gastrin to a much greater extent than acid secretion stimulated by exogenous histamine. One possible explanation for this observation is that endogenous histamine is important in gastrin-mediated acid secretion and that isoprenaline and related beta-adrenoreceptor agonists block gastric mucosal histamine release. This possibility was tested in the present study in gastric lumen-perfused anaesthetized rats. Intravenous infusion of isoprenaline (12 microgram kg-1 h-1) inhibited maximal, pentagastrin-stimulated acid output by 50-70% (P less than 0.01), but had no significant inhibitory effect on the maximal acid secretory response to histamine. In contrast to its inhibitory effect on gastrin-stimulated acid output, isoproterenol had no effect on gastric histamine output during pentagastrin infusion. We conclude that isoprenaline selectively inhibits gastrin-stimulated acid secretion in the rat, as in the dog, and by a mechanism other than inhibiting gastric histamine release.

Dissociation between corticotrophin and catecholamine responses to isoprenaline in humans.

1. The pituitary-adrenocortical, sympathoadrenomedullary and renin-angiotensin-aldosterone systems contribute to circulatory and metabolic homeostasis during stress. One possible site of co-ordination of these systems is the beta-adrenoceptor. 2. To determine whether circulating beta-adrenoceptor agonists can act hormonally to stimulate these systems simultaneously, plasma concentrations of corticotrophin (ACTH), noradrenaline, adrenaline and plasma renin activity were measured during graded intravenous infusions of isoprenaline in 20 people. 3. Administration of isoprenaline caused dose-related increases in noradrenaline (94% at the highest dose) and renin activity (189%), but decreases in ACTH (25%) and adrenaline (20%), findings inconsistent with simultaneous activation of these systems by circulating beta-adrenoceptor agonists.

Vagal activity is increased during intravenous isoprenaline infusion in man.

Eight healthy normal subjects (19-23 years) received graded intravenous isoprenaline infusions PRE- and POST-atropine, 0.04 mg/kg i.v. The adequacy of atropinization was tested with bolus intravenous injections of phenylephrine. PRE-atropine, isoprenaline caused an increase in heart rate and systolic pressure, but a decrease in diastolic pressure with little change in mean pressure (+32.8 +/- 3.0 beats/min, +18.9 +/- 3.0 mm Hg, -13.5 +/- 1.9 mm Hg, -2.7 +/- 1.9 mg Hg respectively at isoprenaline 2 micrograms/min). POST-atropine, the increase in heart rate was enhanced, the rise in systolic pressure abolished and the falls in diastolic and mean pressures exaggerated (+47.0 +/- 2.8 beats/min, -8.9 +/- 2.9 mm Hg, -27.3 +/- 2.1 mm Hg, -21.1 +/- 1.9 mm Hg, respectively at isoprenaline 2 micrograms/min). During an isoprenaline infusion, when the heart rate and blood pressure changes are stable, there is an increase rather than a decrease in cardiac vagal tone.