Isoprenaline Infusion Research Articles

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.

Beta-adrenergic control of plasma glucose and free fatty acid levels in the air-breathing African catfishClarias gariepinusBurchell 1822

In several water-breathing fish species, beta-adrenergic receptor stimulation by noradrenaline leads to a decrease in plasma free fatty acid (FFA) levels, as opposed to an increase in air-breathing mammals. We hypothesised that this change in adrenergic control is related to the mode of breathing. Therefore, cannulated air-breathing African catfish were infused for 90 min with noradrenaline or with the nonselective beta-agonist, isoprenaline. To identify the receptor type involved, a bolus of either a selective beta1-antagonist (atenolol) or a selective beta2-antagonist (ICI 118,551) was injected 15 min prior to the isoprenaline infusion. Both noradrenaline and isoprenaline led to an expected rise in glucose concentration. Isoprenaline combined with both the beta1- and beta2-antagonist led to higher glucose concentrations than isoprenaline alone. This could indicate the presence of a stimulatory beta-adrenoceptor different from beta1 and beta2-adrenoceptors; these two receptors thus seemed to mediate a reduction in plasma glucose concentration. Both noradrenaline and isoprenaline led to a significant decrease in FFA concentration. Whereas the beta1-antagonist had no effect, the beta2-antagonist reduced the decrease in FFA concentration, indicating the involvement of beta2-adrenoceptors. It is concluded that the air-breathing African catfish reflects water-breathing fish in the adrenergic control of plasma FFA and glucose levels.

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.

Diagnosis and Treatment of Low Systemic Blood Flow in Preterm Infants

After completing this article, readers should be able to: 1. Delineate the short- and long-term adverse outcomes associated with low systemic blood flow. 2. Explain why it is not appropriate to use blood pressure and population criteria for hypotension to determine which infants who have low systemic blood flow need cardiovascular support. 3. Describe the various hemodynamic states in neonates and the assessment that is useful in allowing discrimination between these states. 4. Characterize the hemodynamic effects of dopamine and dobutamine in neonates. 5. Delineate the most common characteristics of infants who fail to maintain superior vena cava flows despite the use of inotropes. Low systemic blood flow (SBF) commonly occurs in preterm infants who have respiratory distress in the first postnatal day. Such low flows are strongly associated with neonatal morbidity, including peri/intraventricular hemorrhage (P/IVH), developmental impairments, and mortality. Diagnosing which infants have low SBF is problematic; use of blood pressure (BP) and signs of poor tissue perfusion, including capillary refill times (CRT), poor renal function, and acidosis, results in substantial delays in the initiation of cardiovascular support and a proportion of affected infants missing treatment. The traditional approach to cardiovascular support of the preterm infant has been to identify infants who have hypotension and to use agents, particularly dopamine, titrated to improve BP. However, this strategy may not be the best for improving SBF, and it is yet to be demonstrated that this approach improves neonatal outcomes. This review focuses on identifying which infants have low SBF or organ blood flow, discusses mechanisms for low flows, and examines potential therapies for treating or preventing low flow. Cardiovascular compromise occurs in a number of clinical scenarios in preterm infants, but it is most common on the first postnatal day. Not all infants who have low SBF will be suspected based on clinical signs, including …

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.

The effect of isoprenaline infusion on renal renin and angiotensinogen gene expression in the anaesthetised rat.

In this study, we investigated the ability of acute infusions of isoprenaline to alter renin and angiotensinogen gene expression in the kidney of rats anaesthetised with chloralose-urethane. Groups of rats received I.V. infusions of either saline or the beta-adrenoceptor agonist isoprenaline at 400 ng x kg(-1) x min(-1) for 4 h. The isoprenaline infusion caused a sustained decrease in mean blood pressure of approximately 20 mmHg (P < 0.01), an increase in heart rate of 50 beats x min(-1) (P < 0.01) and reductions in urine flow and sodium excretion of 80-90 % (both P < 0.01). Renal blood flow and glomerular filtration rate were transiently reduced by 21 % (P < 0.01) and 61 % (P < 0.001), respectively, in the first hour, recovering to baseline levels after 4 h of infusion. At the end of the study, plasma renin activity was raised approximately 6-fold (P < 0.01) while renal renin and angiotensinogen mRNA levels were 1.8- and 1.5-fold higher (both P < 0.05) compared to the control group (saline infusion). The isoprenaline-induced renin secretion could have been mediated via the activation of beta-adrenoceptors resulting in the exocytosis of renin-containing granules, with a smaller contribution being due to reduced renal haemodynamics. The increase in renal renin gene expression in response to isoprenaline was probably due primarily to the intracellular signalling processes acting directly on nuclear mechanisms. Similarly, the increased renal angiotensinogen gene expression most probably reflected a direct action of the isoprenaline. These findings provide evidence that catecholamines are involved in mechanisms that rapidly alter the expression of the genes of the renin-angiotensin system within the kidney.

Intracoronary β2 receptor activation induces dynamic local t-PA release in the pig

To investigate beta2 -adrenergic agonist-mediated effects on coronary fluxes of local fibrinolytic factors, healthy anaesthetised and instrumented pigs (n=10) were studied during infusion of isoprenaline (IPR) into the left main coronary artery. Coronary net fluxes of total t-PA antigen, active t-PA and total PAI-1 antigen were determined at baseline and at 3, 5, 7 and 10 minutes of IPR infusion. During IPR, net release of total t-PA increased in a biphasic pattern with transiently high levels at 3 (+440 %) and 7 minutes (+620%) and returned towards baseline at 10 minutes. Net coronary release of active t-PA increased with maximum levels at 3 minutes (+50%). Baseline coronary net flux of total PAI -1 showed a decrease which was most pronounced at 10 minutes. To conclude, a fast beta2 agonist-mediated local release of t-PA into the coronary vasculature was demonstrated. For total t-PA, this response was characterised by a biphasic release profile.

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.

The fate of [U-(13)C]palmitate extracted by skeletal muscle in subjects with type 2 diabetes and control subjects.

The current study investigated the fate of a [U-(13)C]palmitate tracer extracted by forearm muscle in type 2 diabetic and control subjects. We studied seven healthy lean male subjects and seven obese male subjects with type 2 diabetes using the forearm muscle balance technique with continuous intravenous infusion of the stable isotope tracer [U-(13)C]palmitate under baseline conditions and during intravenous infusion of the nonselective beta-agonist isoprenaline (ISO; 20 ng *kg(-1) lean body mass* min(-1)). In skeletal muscle of control subjects, there was a significant release of (13)C-labeled oxidation products in the form of (13)CO(2) (15% of (13)C uptake from labeled palmitate) and a significant release of (13)C-labeled glutamine (release of (13)C-labeled atoms from glutamine was 6% of (13)C uptake from labeled palmitate), whereas in type 2 diabetic subjects there was no detectable release of (13)CO(2) and (13)C-glutamine, despite a significant uptake of [U-(13)C]palmitate (60% of control value). There was net uptake of arterial (13)C-labeled glutamate by forearm muscle in both groups. Also, the ISO-induced increase in arterial glutamine enrichment and arterial concentration of (13)C-glutamine was more pronounced in the diabetic group relative to control subjects. In view of the diminished ISO-induced release of (13)C-glutamine from type 2 diabetic muscle, the latter data indicate that more [U-(13)C]palmitate entered the liver in the diabetic group and was incorporated into newly synthesized glutamine and glutamate molecules. Thus, the lack of release of (13)C-labeled oxidation products by type 2 diabetic muscle during beta-adrenergic stimulation, despite significant [U-(13)C]palmitate uptake, indicates differences in the handling of fatty acids between type 2 diabetic subjects and healthy control subjects.

Effects of verapamil and elgodipine on isoprenaline-induced metabolic responses in rabbits

Verapamil (0.17 μg kg −1 min −1 intravenous, i.v.) but not elgodipine (35 ng kg −1 min −1) modestly enhanced the weak blood glucose increase induced by the i.v. infusion of isoprenaline (0.3 μg kg −1 min −1) in conscious rabbits. However, elgodipine but not verapamil suppressed the increase in circulating insulin evoked by the agonist. Both drugs enhanced the rise in plasma lactate mediated by isoprenaline but only elgodipine potentiated the lipolytic effect of the agonist. In isolated islets elgodipine (10 −6 M) blocked forskolin (10 −6 M)-induced insulin release. However, in rabbit adipocytes elgodipine potentiated both glycerol release and cAMP accumulation induced by isoprenaline (10 −8–10 −6 M). Excess K + (40–60 mM) did not alter basal lipolysis or the response to isoprenaline in either rabbit or mouse adipocytes. Therefore, Ca 2+ influx through L-type Ca 2+ channels does not seem to play a significant role in the lipolytic effect of isoprenaline. Metabolic alterations found with Ca 2+ channel antagonists were of minor intensity and probably devoid of pathological implications.

Induction of Cardiac Fibrosis by Transforming Growth Factor-β1

The role of transforming growth factor-β1 (TGF-β1) in the production and deposition of collagens and in the induction of gene expression in the myocardium in relation to the development of myocardial fibrosis will be discussed. Very low expression of TGF-β1 and collagen type I and III mRNA is seen in the normal rat heart. Both expressions are markedly increased in the infarcted heart and the levels of TGF-β1 mRNA precedes increases in mRNA levels for extracellular matrix (ECM) proteins, suggesting a possible role of TGF-β1 in remodeling processes in the myocardium. The TGF-β1 expression is normally only transient since continuous TGF-β1 overexpression seems to promote nonadaptive cardiac hypertrophy and myocardial fibrosis. In vitro, TGF-β1 induces an increase in collagen production and secretion and enhances the abundance of mRNA levels for collagen type I and III in rat cardiac fibroblasts in culture. TGF-β1 also stimulates in vivo the expression of ECM proteins and in vivo gene transfer of TGF-β1 can induce myocardial fibrosis. Increased myocardial TGF-β1 and ECM protein mRNA are found in myocardial fibrosis induced by angiotensin II infusion, by noradrenaline treatment, by isoprenaline infusion, and by long-term blockade of NO synthesis. In vivo antagonism of TGF-β1 by neutralizing anti-TGF-β1 antibodies or by proteoglycans prevents the increase in gene expression of ECM proteins and inhibits myocardial fibrosis, suggesting that the increases in matrix protein production and fibrosis are mediated by TGF-β1.

Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle.

In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during beta-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-(13)C]palmitate after an overnight fast and during infusion of the nonselective beta-agonist isoprenaline (Iso, 20 ng. kg lean body mass(-1) x min(-1)). Additionally, activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both during fasting and Iso infusion, the tracer balance data showed that forearm muscle FFA uptake (Con vs. type 2: fast 449+/-69 vs. 258 +/-42 and Iso 715+/-129 vs. 398+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05) and FFA release were lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type 2: Iso 446 +/- 274 vs. 16+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05). The net forearm glycerol release was increased in type 2 diabetic subjects (P< 0.05), which points to an increased forearm lipolysis. Additionally, skeletal muscle cytoplasmatic FABP content and the activity of muscle oxidative enzymes were lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma FFA are impaired in the forearm muscles of type 2 diabetic subjects in the overnight fasted state with and without Iso stimulation.

Blockade of isoprenaline-induced fluid and protein secretion by the mandibular glands of the red kangaroo, Macropus rufus, with selective antagonists

Selective and non-selective β-adrenoceptor antagonists were used to block the increases in fluid and protein secretion caused by sympathomimetic stimulation of the mandibular gland of red kangaroos during intracarotid infusion of isoprenaline. Atenolol or ICI118551 at antagonist:agonist ratios up to 300:1 caused increasing but incomplete blockade of fluid secretion and protein release. Both selective antagonists had equal potency and both antagonists were more effective at blocking protein release than at blocking fluid secretion. Consequently, the mechanisms underpinning fluid secretion are more sensitive to β-sympathomimetic stimulation than those causing protein release. Propranolol at antagonist:agonist ratios of 300:1 was more potent than the selective antagonists, almost totally blocking the increases in fluid secretion and protein release. The data are consistent with the acini of the kangaroo mandibular gland having both β 1- and β 2-adrenoceptors and with the increased fluid secretion and protein release by isoprenaline being mediated by both receptor subtypes.

Beta-Adrenergic regulation of proinflammatory cytokines in humans.

To investigate the effects of beta-adrenergic stimulation on IL-6 secretion in humans, and to determine the potential contribution to this response of adipocytes and peripheral blood cells (PBC). Experimental study in 8 human volunteers, and in vitro studies on murine adipocyte cell-line, 3T3.L1 and 3T3.F442A, and human PBC. Plasma IL-6 and TNFalpha responses to isoprenaline infusion. Cytokine secretion from differentiated adipocyte cell-lines and PBC in response to isoprenaline. Plasma IL-6 levels increased ninefold (median) by 180 min (baseline median 0.51 [interquartile range 0.47-1.4] vs 180 mins 4.53 [2.58-5.69] pg ml(-1), P=0.01). One hour after infusion, IL-6 levels (2.9 [1.27-3.98]) were lower than at 180 min (P=0.05), but higher than baseline (P=0.01). TNFalpha levels were unchanged. Differentiated adipocytes incubated in isoprenaline (0-0.1 microM) released significantly increased amounts of IL-6 whereas no response was elicited from PBC. The induction of IL-6 observed in vivo may be attributed to the beta-adrenergic stimulation of IL-6 release specifically from adipocytes, as opposed to circulating blood cells.

No difference in the lipolytic response to β-adrenoceptor stimulation in situ but a delayed increase in adipose tissue blood flow in moderately obese compared with lean men in the postexercise period

This study was undertaken to determine the effect of previous exercise on adipose tissue responsiveness to beta-adrenoceptor stimulation and on adipose tissue blood flow (ATBF). Eight lean and 8 obese men (body mass index [BMI], 23.6 +/- 2.1 [SD] v 29.0 +/- 1.9 kg x m(-2)) were investigated with abdominal subcutaneous microdialysis and 133Xe clearance. A stepwise isoprenaline infusion (10(-8), 10(-7), and 10(-6) mol x L(-1)) was administered in situ in the microdialysis catheter before and 2 hours after a submaximal exercise bout (90 minutes of cycling at 55% of maximal O2 uptake). No differences in the response (increase in interstitial glycerol v preinfusion level) to isoprenaline infusions were found between the 2 groups. In both groups, there was no difference in the response to postexercise versus preexercise infusion. When the vasodilating agent hydralazine (0.125 g x L(-1)) was infused into the microdialysis catheter to control for the vascular effects of isoprenaline, an interaction effect between exercise and isoprenaline dose was found. Analyses showed an attenuated response to the high isoprenaline dose after exercise (lean, 251 +/- 42 [SE] micromol x L(-1); obese, 288 +/- 77 micromol x L(-1)) versus before exercise (lean, 352 +/- 62 micromol x L(-1), P = .045 v after; obese, 380 +/- 94 micromol x L(-1), P = .021 v after), indicating a desensitization of lipolysis to beta-adrenoceptor stimulation. ATBF and arterial plasma glycerol increased after exercise in both groups, but the increase was delayed in obese subjects. Arterial plasma insulin was higher in the obese versus lean subjects at all times, and decreased during recovery in both groups. In conclusion, abdominal subcutaneous adipose tissue responsiveness to beta-stimulation is not enhanced postexercise in lean and obese men, whereas previous exercise increases ATBF. Furthermore, the data suggest slower lipid mobilization postexercise and resistance to the antilipolytic effect of insulin in the obese.

Endogenous renin and related short-term blood pressure variability in the conscious rat

This study was designed to investigate, by use of spectral analysis, the blood pressure variability changes induced in the conscious rat by activation of plasmatic renin activity. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform the infusions, and with a femoral artery catheter to measure blood pressure and heart rate. Secretion of renin was induced using β-adrenoceptor stimulation produced by isoprenaline. A first group ( n=8) was infused with isoprenaline: 0.003, 10, 100 and 300 ng/kg/min, at a rate of 20 μl/min. A second group ( n=8) was given a bolus injection of the angiotensin AT 1 receptor antagonist, valsartan (2 mg/kg, i.a.), prior to isoprenaline infusions. The lack of effect of infusion per se was checked in additional animals ( n=8) infused with saline only (20 μl/min). Five other groups of animals were prepared with arterial catheters as mentioned previously. Each group received one concentration of infused isoprenaline and samples of blood were collected for further determinations of plasma renin activity and catecholamine concentrations. Blood pressure recordings were analysed using the fast Fourier transform on 2048 points time series (204.8 s). Isoprenaline increased plasma renin activity and did not modify plasma catecholamine concentrations. The low-frequency (0.02–0.2 Hz) component of the systolic blood pressure variability was amplified by isoprenaline (10 ng/kg/min isoprenaline: 4.16±0.62 mm Hg 2 vs. 2.90±0.44 mm Hg 2 for control value, P<0.05), a concentration that did not alter either blood pressure or heart rate levels. Isoprenaline lowered blood pressure and increased heart rate, starting at concentrations of 100 ng/kg/min. Valsartan, whose principal effect was generation of tachycardia (+25 bpm) modified neither blood pressure levels nor blood pressure variability. Valsartan prevented the amplification of the low-frequency oscillations of systolic blood pressure induced by isoprenaline (10 ng/kg/min isoprenaline: 2.53±0.38 mm Hg 2 vs. 2.20±0.25 mm Hg 2 for control value (valsartan, ns). We conclude that a moderate increase of plasma renin activity enhanced systolic blood pressure variability in the low-frequency range, without affecting blood pressure and heart rate levels.

Effect of β-antagonists on isoprenaline-induced secretion of fluid, amylase and protein by the parotid gland of the red kangaroo, Macropus rufus

Selective and non-selective β-adrenoceptor antagonists were used to block the increases in fluid, protein and amylase secretion caused by sympathomimetic stimulation of the parotid gland of red kangaroos during intracarotid infusion of isoprenaline. ICI118551 at antagonist/agonist ratios up to 300:1 caused increasing but incomplete blockade of fluid secretion, and protein/amylase release. Atenolol at antagonist/agonist ratios up to 300:1 was only marginally more potent than ICI118551 at blocking the fluid, protein and amylase responses. Propranolol at antagonist/agonist ratios of 30:1 was as effective at blocking fluid and protein secretion as the highest ratios of either atenolol or ICI118551. Simultaneous administration of atenolol (30:1) with ICI118551 (30:1) was not as potent as propranolol (30:1). Thus, the β-adrenoceptor/s in the acini of the kangaroo parotid gland appear to have antagonist-binding affinities atypical of those found for eutherian tissues. The data are consistent with the gland possessing either a single anomalous β-adrenoceptor or functional β 2-receptors in addition to the β 1-receptors which are characteristic of eutherian salivary glands.

Microdialysis assessment of local adipose tissue lipolysis during beta-adrenergic stimulation in upper-body-obese subjects with type II diabetes.

The present study was designed to investigate indicators of abdominal adipose tissue lipolysis (microdialysis), and subcutaneous adipose tissue blood flow and whole-body lipolysis, in obesity-associated type II diabetes during overnight-fasted conditions (baseline) and during intravenous infusion of the non-selective beta-agonist isoprenaline. Basal subcutaneous adipose tissue blood flow and isoprenaline-induced increases in adipose tissue blood flow were not significantly different between subjects with type II diabetes and non-obese, non-diabetic controls. Adipose tissue interstitial glycerol concentrations were significantly higher in subjects with type II diabetes compared with controls (P<0. 01), and during isoprenaline infusion there was a decrease in interstitial glycerol in both groups (P<0.001). Arterial glycerol concentrations were higher in subjects with type II diabetes compared with controls (P<0.05), whereas the increases in arterial glycerol concentration in response to isoprenaline infusion were of a similar magnitude in the two groups. Estimated subcutaneous adipose tissue glycerol release was not significantly different between the groups (controls and subjects with type II diabetes: baseline, -129+/-32 and -97+/-72 micromol.min(-1).100 g(-1) adipose tissue respectively; isoprenaline, -231+/-76 and -286+/-98 micromol. min(-1).100 g(-1) respectively). Values for fat oxidation were not significantly different between groups, whereas the isoprenaline-induced increase in fat oxidation tended to be less pronounced in subjects with type II diabetes compared with controls (0.022+/-0.008 and 0.038+/-0.003 g/min respectively; P=0.058). Thus estimated basal subcutaneous adipose tissue glycerol release, expressed per unit of fat mass, is not different in controls and in subjects with type II diabetes. Additionally, the isoprenaline-induced increases in indicators of local abdominal subcutaneous adipose tissue, systemic lipolysis and abdominal adipose tissue blood flow responses were comparable in obese subjects with type II diabetes and in controls. The last two findings contrast with previous data from obese subjects, indicating that the regulation of lipolysis may differ in obesity and obesity-associated type II diabetes.

Electrophysiological effects of flecainide and propafenone on atrial fibrillation cycle and relation with arrhythmia termination

OBJECTIVES(1) To investigate the electrophysiological effects of flecainide and propafenone during atrial fibrillation, and their relation to arrhythmia termination; (2) to investigate the effects of isoprenaline on atrial fibrillation in...

Functional analysis of desensitization of the beta-adrenoceptor signalling pathway in rat cardiac tissues following chronic isoprenaline infusion.

1. This study examined beta-adrenoceptor signalling in cardiac tissues following infusion of isoprenaline (400 microg kg(-1) h(-1)) or vehicle to rats for 14 days. 2. Isoprenaline infusion caused marked hypertrophy of atria and ventricles and reduced the resting rate of spontaneously beating right atria and the basal force of left atrial contraction. 3. In spontaneously beating right atria, concentration-response curves to isoprenaline and forskolin were shifted 7.9 and 3.2 fold to the right following treatment whereas responses to the cyclic AMP analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3', 5'-cyclic monophosphorothioate were unchanged. 4. In electrically driven left atria, concentration-response curves to isoprenaline and forskolin were shifted 4 fold to the right and maximum responses reduced. Responses to dibutyryl cyclic AMP were shifted 3.2 fold to the right but those to Ca2+ were unchanged. 5. Inotropic responses of left and right ventricular papillary muscles to isoprenaline were abolished and markedly reduced respectively by isoprenaline treatment. Responses to forskolin were shifted 5 fold to the right. Responses to dibutyryl cyclic AMP were shifted to the right 3.2 and 2 fold in left and right ventricular papillary muscles. Responses to isobutyl methyl xanthine were shifted to the right 15.8 and 6.3 fold in left and right papillary muscles whereas those to Ca2+ were not significantly altered. 6. This study indicates differences in beta-adrenoceptor desensitization in different regions of the heart following chronic infusion of isoprenaline. Chronotropic responses showed impaired signalling between the receptor and adenylate cyclase whereas inotropic responses exhibited additional desensitization at the level of cyclic AMP dependent protein kinase.