Sympathoadrenal Responses to Bronchoconstriction in Asthma: An Invasive and Kinetic Study of Plasma Catecholamines

1995 ◽  
Vol 88 (4) ◽  
pp. 439-446 ◽  
Author(s):  
Kjell Larsson ◽  
Per Carlens ◽  
Sture Bevegård ◽  
Paul Hjemdahl

1. Bronchoconstriction does not seem to be a stimulus for sympathoadrenal activation, as judged by venous plasma concentrations of noradrenaline, adrenaline or neuropeptide Y-like immunoreactivity. However, venous measurements have methodological drawbacks. In the present study arterial and mixed venous (pulmonary arterial) levels of these variables were determined before and after histamine-induced bronchoconstriction in non-medicated asthmatic subjects. In addition, noradrenaline kinetics in plasma (isotope dilution) and the pulmonary overflows of noradrenaline and neuropeptide Y-like immunoreactivity were determined. 2. Histamine inhalation induced bronchoconstriction; forced expiratory volume in 1 s decreased by 38.7% ± 4.1% (SE) and arterial Po2 by 3.0 ± 0.9 kPa. This acute bronchoconstriction induced significant elevations of arterial and mixed venous plasma noradrenaline from ≤1.18 nmol/l to ≥1.40 nmol/l. The clearance of NA from plasma increased marginally. Thus, the arterial plasma NA response was due to increased spillover of noradrenaline to plasma (from 1.80 ± 0.18 to 2.52 ± 0.36 mmol min−1/m2 at maximal bronchoconstriction, with a subsequent further increase). There were no elevations of adrenaline or neuropeptide Y-like immunoreactivity in arterial plasma. 3. No sympathetic activation could be demonstrated in the lungs (pulmonary noradrenaline or neuropeptide Y-like immunoreactivity overflow), and no alterations in pulmonary vascular resistance or cardiac output were observed. Neither arterial nor mixed venous plasma concentrations of adrenaline were influenced by bronchoconstriction. 4. Acute bronchoconstriction thus leads to peripheral sympathetic activation (possibly due to the increased work of breathing) which does not involve the lungs. Adrenaline is not secreted in response to induced bronchoconstriction, and thus is of no functional importance as a counter-regulatory hormone in this situation.

1988 ◽  
Vol 254 (3) ◽  
pp. R470-R477 ◽  
Author(s):  
S. B. Jones ◽  
M. V. Westfall ◽  
M. M. Sayeed

Fasted, conscious male rats, prepared with arterial and venous cannulas, were given doses (10(10)-10(11) organisms/kg) of live Escherichia coli bacteria. Heart rate and blood pressure were recorded, and arterial plasma samples were taken preinjection and at 30, 180, and 360 min after bacterial administration. Plasma was analyzed for lactate, glucose, norepinephrine (NE), and epinephrine (E). Rats given E. coli were normotensive but with significant tachycardia (P less than 0.05 vs. saline). Plasma NE and E levels increased severalfold during bacteremia (P less than 0.05 for all comparisons). Rats were euglycemic but had a sixfold increase in lactate 6 h (P less than 0.05) after E. coli treatment. Additional rats were subjected to the same protocol but had been made tolerant to bacterial endotoxin by multiple injections over the course of several days. Endotoxin-tolerant rats were also tolerant to live E. coli administration (P less than 0.05, 24 h survival) and had significantly reduced levels of E and NE at 6 h compared with nontolerant bacteremic rats (P less than 0.05). Increases in heart rate and plasma lactate were not significant in endotoxin-tolerant rats. These results suggest profound sympathetic activation during acute bacteremia with attenuated activation in endotoxin-tolerant rats. Tolerance appears to reduce the afferent stimuli that are presumably activated during the course of bacteremia.


1998 ◽  
Vol 274 (3) ◽  
pp. R626-R634 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Bengt Rundqvist ◽  
Peter Friberg

This study assessed whether the mechanisms regulating cardiac norepinephrine (NE) synthesis with changes in NE release are influenced by functions of sympathetic nerves affecting transmitter turnover independently of transmitter release. Differences in arterial and coronary venous plasma concentrations of NE and its metabolites and of dihydroxyphenylalanine (DOPA), the immediate product of tyrosine hydroxylase (TH), were examined before and during cycling exercise. Relative increases during exercise in cardiac tyrosine hydroxylation (as reflected by the %increase in cardiac DOPA spillover) matched closely corresponding increases in NE turnover, but were much lower than increases in NE release. The much larger relative increases in release than turnover of NE were largely attributable to the extensive contribution to transmitter turnover from intraneuronal metabolism of NE leaking from storage vesicles. This contribution remains unchanged during sympathetic activation so that the relative increase in NE turnover is much smaller than that in exocytotic release of NE. To replenish the NE lost from stores during sympathetic activation, TH activity need increase only in proportion to the smaller increase in turnover rather than the larger relative increase in release. The ability to “gear down” increases in tyrosine hydroxylation relative to increases in NE release provides sympathetic nerves the capacity for a more extended range of sustainable release rates than otherwise possible.


1989 ◽  
Vol 123 (2) ◽  
pp. 295-302 ◽  
Author(s):  
M. E. Symonds ◽  
D. C. Andrews ◽  
P. Johnson

ABSTRACT Oxygen consumption (VO2), carbon dioxide production (VCO2), heart rate and the arterial plasma concentrations of glucose, non-esterified fatty acids, thyroxine (T4), 3,5,3′-tri-iodothyronine (T3), TSH, insulin, cortisol and GH were measured before and after feeding a formula milk diet to lambs aged 9, 21, 33 and 46 days. In all age groups, VO2, VCO2 and heart rate increased significantly following feeding and this effect was greatest at 9 days of age. Both VO2 and VCO2 before and after feeding decreased with age. Plasma concentrations of T3 before feeding did not change with age, but plasma T3 levels after feeding were significantly higher in lambs aged 9 days compared with 33 and 46 days. There was no effect of feeding on TSH or age on plasma TSH and T4 concentrations. In all age groups, glucose concentration increased after feeding and was paralleled by a rise in insulin concentration. At 9 and 21 days of age plasma glucose and insulin concentrations reached a plateau after the initial postprandial increase and together with a rise in respiratory quotient was indicative of a stimulation of carbohydrate oxidation. Plasma concentrations of GH increased after feeding at 21 days and older, when the mean growth rate was also stimulated by 75%. Basal metabolic rate and dietary-induced thermogenesis both decreased with age and, as a result, metabolism associated with an increase in GH levels after feeding became more efficient in terms of growth rate after 21 days. It is therefore concluded that there are major endocrine and cardiorespiratory changes in response to feeding of the young lamb which are important in stimulating and/or facilitating its growth and development. Journal of Endocrinology (1989) 123,295–302


Hypertension ◽  
1997 ◽  
Vol 29 (1) ◽  
pp. 137-143 ◽  
Author(s):  
Margaret J. Morris ◽  
Helen S. Cox ◽  
Gavin W. Lambert ◽  
David M. Kaye ◽  
Garry L. Jennings ◽  
...  

2016 ◽  
Vol 48 (6) ◽  
pp. 1593-1601 ◽  
Author(s):  
Prathap Pillai ◽  
Yih-Chih Chan ◽  
Shih-Ying Wu ◽  
Line Ohm-Laursen ◽  
Clare Thomas ◽  
...  

Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE and inflammation and preserves/improves lung function when disease is destabilised by staged withdrawal of therapy.18 symptomatic, non-atopic asthmatics were randomised (1:1) to receive omalizumab or identical placebo treatment in addition to existing therapy for 20 weeks. Bronchial biopsies were collected before and after 12–14 weeks of treatment, then the patients destabilised by substantial, supervised reduction of their regular therapy. Primary outcome measures were changes in bronchial mucosal IgE+ cells at 12–14 weeks, prior to regular therapy reduction, and changes in lung function (forced expiratory volume in 1 s) after destabilisation at 20 weeks. Quality of life was also monitored.Omalizumab but not placebo therapy significantly reduced median total bronchial mucosal IgE+ cells (p<0.01) but did not significantly alter median total mast cells, plasma cells, B lymphocytes, eosinophils and plasmablasts, although the latter were difficult to enumerate, being distributed as disperse clusters. By 20 weeks, lung function declined in the placebo-treated patients but improved in the omalizumab treated patients, with significant differences in absolute (p=0.04) and % predicted forced expiratory volume in 1 s (p=0.015).Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE+ mast cells and improves lung function despite withdrawal of conventional therapy.


2007 ◽  
Vol 21 (2) ◽  
pp. 309-314 ◽  
Author(s):  
J. Miholic ◽  
M. Hoffmann ◽  
J.J. Holst ◽  
J. Lenglinger ◽  
M. Mittlböck ◽  
...  

2003 ◽  
Vol 98 (5) ◽  
pp. 1057-1062 ◽  
Author(s):  
Cyrus Motamed ◽  
Riad Menad ◽  
Robert Farinotti ◽  
Krassen Kirov ◽  
Xavier Combes ◽  
...  

Background Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium. Methods After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography. Results Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P &lt; 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P &lt; 0.05). Conclusions A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.


Pharmacology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Alex Guazzi Rodrigues ◽  
Helton Oliveira Campos ◽  
Lucas Rios Drummond ◽  
Umeko Marubayashi ◽  
Cândido Celso Coimbra

<b><i>Aim:</i></b> The aim of this study was to assess the influence of adrenomedullary secretion on the plasma glucose, lactate, and free fatty acids (FFAs) during running exercise in rats submitted to intracerebroventricular (i.c.v.) injection of physostigmine (PHY). PHY i.c.v. was used to activate the central cholinergic system. <b><i>Methods:</i></b> Wistar rats were divided into sham-saline (sham-SAL), sham-PHY, adrenal medullectomy-SAL, and ADM-PHY groups. The plasma concentrations of glucose, lactate, and FFAs were determined immediately before and after i.c.v. injection of 20 μL of SAL or PHY at rest and during running exercise on a treadmill. <b><i>Results:</i></b> The i.c.v. injection of PHY at rest increased plasma glucose in the sham group, but not in the ADM group. An increase in plasma glucose, lactate, and FFAs mobilization from adipose tissue was observed during physical exercise in the sham-SAL group; however, the increase in plasma glucose was greater with i.c.v. PHY. Moreover, the hyperglycemia induced by exercise and PHY in the ADM group were blunted by ADM, whereas FFA mobilization was unaffected. <b><i>Conclusion:</i></b> These results indicate that there is a dual metabolic control by which activation of the central cholinergic pathway increases plasma glucose but not FFA during rest and exercise, and that this hyperglycemic response is dependent on adrenomedullary secretion.


2014 ◽  
Vol 54 (2) ◽  
pp. 187 ◽  
Author(s):  
I. Zulkifli ◽  
Y. M. Goh ◽  
B. Norbaiyah ◽  
A. Q. Sazili ◽  
M. Lotfi ◽  
...  

The present study aimed to provide a comparative analysis of the effects of penetrative stunning, non-penetrative stunning and post-slaughter stunning on biochemical parameters and electroencephalogram (EEG) associated with stress in heifers and steers. Ten animals were assigned to each of the following four treatment groups: (1) animals were subjected to conventional halal slaughter (a clean incision through the structures on the ventral neck at the approximate level of vertebrae C2–C3 – the trachea, oesophagus, carotid arteries and jugular veins) and post-cut penetrating mechanical stun within 10–20 s of the halal cut (U); (2) high-power non-penetrating mechanical stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (HPNP); (3) low-power non-penetrating mechanical percussive stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (LPNP); and (4) penetrative stunning using a captive-bolt pistol humane killer, followed by conventional halal slaughter (P). For each animal, blood samples and electroencephalogram recordings were taken before stunning, post-stunning (if applicable) and post-slaughter, and plasma concentrations of cortisol, adrenocorticotrophic hormone (ACTH), adrenaline, noradrenaline and β-endorphin were determined. Irrespective of the stunning method, except for percentage change in plasma concentrations of noradrenaline, the values of blood parameters attained before and after stunning were not significantly different. The plasma noradrenaline concentration of the HPNP animals was significantly elevated following stunning. Following slaughter, the percentage change of plasma ACTH concentration in the P animals was significantly elevated. Neither stunning method nor sampling time had a significant effect on plasma β-endorphin concentration. On the basis of the EEG results, penetrative stunning seemed to be better in maximising the possibility of post-stunning insensibility, whereas U animals appeared to demonstrate an evident increase in EEG activity which is consistent with the presence of post-slaughter noxious stimuli associated with tissue cut and injury. The U animals had consistently higher, if not the highest, RMS values than did other stunned animals. This indicates a degree of EEG changes associated with stress and pain. On the basis of EEG data, our results suggested that penetrative stunning would be the most reliable method of ensuring insensibility and minimising pain. However, at slaughter, the P animals showed a dramatic elevation in the percentage change of circulating ACTH, suggesting physiological stress response. On a cautionary note, the results are not unequivocal, and it may be that the range of analyses available to researchers at this point of time are not sufficiently specific to allow definitive conclusions to be drawn.


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