Circulating Levels Of Epinephrine Research Articles

Activation of the Bezold-Jarisch Reflex in the Sitting Position for Shoulder Arthroscopy Using Interscalene Block

A retrospective analysis of 116 patients who underwent shoulder arthroscopy in the sitting position with interscalene block (ISB) revealed 20 patients who experienced potentially dangerous vasovagal events characterized by sudden severe hypotension and bradycardia (Group 1). The event occurred 61 +/- 18 min after the block placement. Ninety-six patients (Group 2) did not experience a vasovagal event. Of the patients in Group 2, 18 received beta-adrenergic blockers for increasing heart rate and/or arterial blood pressure (Group 2B) while 78 did not (Group 2A). The number receiving beta-adrenergic blockers was significantly greater than in Group 1 (18/96 vs 0/20, P < 0.05). There were no significant demographic or baseline hemodynamic differences between groups, but the beta-adrenergic blocker and vagal groups showed significantly greater intraoperative peak heart rates (P < 0.05). All patients received epinephrine in their local anesthetic for ISB, incision sites, and articular irrigating solution. Total and weight-corrected epinephrine doses differed significantly between groups (lowest in Group 2A, P < 0.01). Activation of the Bezold-Jarisch reflex, induced by increased circulating epinephrine levels and the sitting position, is the postulated mechanism.

Epinephrine, norepinephrine, and cortisol concentrations in cannulated seawater‐acclimated rainbow trout (Oncorhynchus mykiss) following black‐box confinement and epinephrine injection

The present study investigates the effect of cannulation and chronic‘black‐box’ confinement, as well as epinephrine administration (4–0 μg kg−1), on the degree and time‐course of alterations in trout (Oncorhynchus mykiss) catecholamine and cortisol concentrations. Plasma cortisol concentrations in seawater trout acclimated to 3–6° C reached 104 ng ml−1 1 day after cannulation/confinement and remained elevated above resting levels (8 ng ml−1) until 6 days post‐confinement. Although plasma epinephrine and norepinephrine generally declined over the period of confinement (day 1 approx. 12 nM; day 7 approx. 6 nM), norepinephrine titres were usually higher and more variable. Epinephrine injection caused elevations in plasma epinephrine levels but not in norepinephrine levels; epinephrine titres reaching 107 ± 26 nM (range 65–238 nM) at 2 min post‐injection and returning to pre‐injection levels by 30 min post‐injection. Plasma cortisol increased by 20 ng ml−1 following epinephrine administration. Based on the time‐course for post‐confinement alterations in plasma cortisol, it appears that up to a week may be required before cannulated fish are completely acclimated to ‘black‐box’ confinement. The findings suggest that meaningful results from experiments utilizing epinephrine injection and ‘black‐box confinement are contingent upon: (1) knowledge of circulating epinephrine levels shortly after injection (i.e. within 2 min post‐injection); and (2) an experimental design that takes into account the elevated cortisol titres that are inherent with cannulation/confinement and epinephrine injection.

Somatic Correlates of Adrenergic Activity during Aggression in the Lizard, Anolis carolinensis

Aggressive interactions in Anolis carolinensis result in increased circulating levels of epinephrine (Epi) and norepinephrine (NE) and conspicuous color changes. This activation of the adrenergic component of an acute stress response is externally represented by the darkening of the postorbital eyespot of A. carolinensis. In adult males, this site darkens in response to stressful physical stimulation (trauma, passive restraint) or psychological stimuli, most notably the sight of an aggressively intruding conspecific. Aggressive male A. carolinensis exhibit postorbital eyespot darkening; animals that have a longer latency to expression of this eyespot and those that never show this response were defeated in agonistic interactions. Also, during agonistic interactions, subjects that subsequently win are the first to display eyespot darkening. Plasma catecholamine levels are significantly elevated within 30 see in both combatants. At 30 sec following the determination of the outcome, winning male lizards have plasma NE levels which are higher than those of losers. Castration, however, significantly increases the latency to eyespot darkening and extends its duration. Testosterone levels may therefore enhance the onset of Epi-mediated eyespot darkening as well as other aspects of the endocrine stress response. Elevated androgen levels and more rapid activation of acute catecholamine response increases the likelihood of becoming socially dominant.

Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats

omega-Conotoxin (omega-ctx) was used as a probe for studying the putative role of brain L/N-type Ca2+ channels in regulation of autonomic functions. Rats were injected intracerebroventricularly (icv) with omega-ctx, and hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx (0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior, complex thermoregulatory changes, and motor deficits lasting up to 48 h. Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less than 0.05) associated with increased circulating levels of norepinephrine and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory shock and death. Central administration of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg), neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100 nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type Ca2(+)-channel blockers, respectively, did not cause any behavioral or hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg icv) caused a mild transient pressor response. Pretreatment with the gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined intravenous pretreatment with propranolol and N-methylatropine blocked the omega-ctx effects. Our data suggest that omega-ctx actions in the brain involve central GABAergic mechanisms modulated by yet a different type of Ca2+ channels not characterized by any of the known voltage-operated Ca2+ channels.

Tumor necrosis factor enhances glucose uptake by peripheral tissues.

Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 +/- 0.1 to 3.9 +/- 0.2 mmol/l by 6 h (P less than 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 +/- 2.1 to 32.5 +/- 0.7 mumol.min-1.kg body wt-1 (P less than 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 +/- 2.2 to 32.7 +/- 0.9 mumol.min-1.kg body wt-1, P less than 0.05) and enhanced clearance (5.7 +/- 0.5 to 9.0 +/- 0.6 ml.min-1.kg body wt-1, P less than 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50% fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

The Relationship of Burn-induced Hypermetabolism to Central and Peripheral Catecholamines

The role of brain and circulating catecholamines as mediators of burn-induced hypermetabolism was investigated in two experiments. Following a 30% body surface area full-thickness open-flame burn, rats exhibited a short period (3 to 4 days) of anorexia followed by a more prolonged (several weeks) hyperphagic-hypermetabolic response. During this hypermetabolic period, norepinephrine concentrations were increased in the brain and circulating epinephrine levels were elevated. Depletion of brain norepinephrine using 6-hydroxydopamine led to increased body weight gain, but did not increase resting energy expenditure in burned rats. Similarly, the reduction of circulating catecholamines through removal of the adrenal medulla resulted in a decreased loss of body weight and only slight reductions in resting energy expenditure. Therefore, these results suggest that although brain norepinephrine and circulating epinephrine have a role in the full expression of hypermetabolism, these compounds do not appear to be major mediators of this response to burn trauma.

The Effects of Chronic Administration of Adrenaline on the Function and Number of Adrenoceptors in the Rabbit

Chronic (10-day) intravenous infusions of adrenaline (0.05 mumol/kg/h) were given to rabbits via osmotic minipumps implanted at the femoral vein. Blood pressure, heart rate, and plasma catecholamine concentrations were measured five times during the period of infusion. Tenfold elevations in circulating adrenaline levels were achieved within 24 h of commencing infusion and maintained throughout the study. This increase in plasma adrenaline was not accompanied by significant changes in blood pressure or heart rate. Rabbits were killed after 10 days: blood was withdrawn for platelet aggregation studies. Kidney, heart, and lung were also collected and alpha 2-adrenoceptor number on platelets and kidney measured using [3H]yohimbine. Beta adrenoceptors on platelets, lymphocytes, heart, and lung were quantified using [125I]iodocyanopindolol. Adrenaline infusion led to a significant reduction in platelet aggregation responses to adrenaline (0.001-100 microM), together with a decrease in alpha 2-adrenoceptor number on platelets, but no significant decrease in kidney alpha 2-adrenoceptors. A significant decrease in the density of beta adrenoceptors on heart and lung membranes was observed with no reduction in platelet and lymphocyte beta-adrenoceptor number. Thus adrenaline-induced down-regulation of adrenoceptors in the rabbit was dependent on the location and subtype of adrenoceptor.

Facilitation of nerve stimulation evoked noradrenaline overflow by isoprenaline but not by circulating adrenaline in the dog in vivo

The influence of isoprenaline and adrenaline on the overflow of endogenous noradrenaline evoked by sympathetic nerve stimulation was studied in canine blood perfused gracilis muscle in situ . Neuronal uptake was inhibited by desipramine. Local i.a. infusions of isoprenaline enhanced stimulation evoked noradrenaline overflow by 32±10 % (P <0.05), indicating the existence of prejunctional facilitatory β-adrenoceptors. This effect of isoprenaline was not antagonized by β 1-adrenoceptor blockade and does not seem to be related to the vasodilatation caused by isoprenaline. In a second series of experiments circulating adrenaline levels were raised by i.v. infusions from basal levels of 0.4±0.2 nM to 1.7±0.2 and 6.3±0.6 nM, respectively, in arterial plasma. Adrenaline elicited vasodilatation in the gracilis muscle (19±3 and 28±5 % increases in vasdcular conductance, respectively), indicating activation of postjunctional β 2-adrenoceptors, without influencing nerve stimulation evoked noradrenaline overflow. Thus, our results support the existence of a prejunctional β 2-adrenoceptor mediated mechanism facilitating noradrenaline release in vivo , but provide no evidence to support the idea that physiologically relevant increases in circulating adrenaline levels enhance noradrenergic neurotransmission in skeletal muscle.

Alterations in the myocardial β-adrenoceptor system of streptozotocin-diabetic rats

Previous investigations in our laboratory revealed subsensitivity of right ventricular tissue, isolated from one month STZ-diabetic rats, to the inotropic effects of isoproterenol. The present study was concerned with the characterization of this subsensitivity phenomenon. Observations of supersensitivity to methoxamine accompanied by decreased responsiveness to glucagon without a change in responsiveness to forskolin suggested a specific effect of diabetes on pathways involving receptor-mediated activation of adenylate cyclase. Radioligand binding analysis further revealed a specific decrease in the population of the high affinity state of the β-adrenoceptor. Since the high affinity receptor state is a necessary intermediate for adenylate cyclase activation and enhanced myocardial contractility, it is proposed that the specific decrease in the high affinity population of the β-adrenoceptor contributes to myocardial subsensitivity to isoproterenol observed in the diabetic animals. It is further proposed that the decrease in receptor population is related to increases in circulating epinephrine levels which were evident in the diabetic animals.

Bronchodilatation and inhibition of allergen-induced bronchoconstriction by circulating epinephrine in asthmatic subjects

The influence of circulating epinephrine on basal bronchial tone and its ability to counteract the bronchial response to specific allergen challenge was investigated in eight patients with extrinsic seasonal asthma. A pretrial bronchial allergen challenge was positive for birch or timothy pollen. The patients were free from all medication at least 1 wk before experiments. On two separate occasions placebo (saline) or epinephrine (0.25 and 0.50 nmol ×-1 × min -1) were infused. Epinephrine caused dose-dependent increases in end expiratory flow rates but did not influence peak expiratory flow rates or specific airway conductance, indicating dilatation of predominantly smaller airways. During placebo infusions allergen provocation induced clear-cut bronchoconstriction but no increase in circulating epinephrine levels. Elevation of circulating epinephrine (to 5 to 6 nmol/L in venous plasma) counteracted the allergen-induced bronchoconstriction. During epinephrine infusions all patients tolerated higher allergen doses than during placebo infusions. When the allergen dose was increased sufficiently to cause bronchoconstriction also during epinephrine infusions, the bronchoconstriction observed was similar in terms of changes in lung function parameters but less responsive to treatment with a high dose of the β-2-agonist, salbutamol. This may have therapeutic implications since protection offered by treatment with, e.g., β2-agonists, may lead to exposure to higher allergen doses and similarly aggravated asthmatic reactions when they do occur despite this treatment.

HYPOKALAEMIA INDUCED BY INHALATION OF FENOTEROL

The effect of inhalation of fenoterol, a β 2-agonist, on plasma potassium was studied in four groups of four healthy young subjects. Group I received 3 times 2 puffs (0·2 mg fenoterol/puff), group II 3 times 3 puffs, and group III 3 times 4 puffs. Group IV received 3 times 4 puffs of a placebo, according to the group III schedule. The puffs were given at 30-min intervals. Plasma potassium levels decreased significantly in subjects who received fenoterol: the decrease was 0·4±0·3 (SD) mmol/l in group I, 0·5±0·2 mmol/l in group II and 0·9±0·1 mmol/l in group III. In the placebo group plasma potassium levels were unchanged. Inhalation of β 2-agonists may be dangerous, especially in patients under stress-eg, during an acute asthmatic attack, when the plasma potassium concentration would already be subnormal as the result of raised circulating adrenaline levels.

CIRCULATING CATECHOLAMINE, THYROTROPHIN, THYROID HORMONE AND PROLACTIN RESPONSES OF NORMAL SUBJECTS TO ACUTE COLD EXPOSURE

The responses of circulating catecholamines, TSH, thyroid hormones and prolactin to 30 min of acute cold exposure (4 degrees C) were measured in eight normal volunteers over a 2 h period. There was a rise in circulating noradrenaline, TSH, T4 and T3 levels and a fall in circulating prolactin in the subjects studied, but no change in circulating adrenaline levels nor any alteration in the T4/T3 ratio. The thyroid axis of normal individuals can respond rapidly to acute cold exposure. In addition, the increased plasma noradrenaline levels accompanied by unaltered adrenaline levels suggest that the stimulus exerted by cold does not evoke a generalised stress response, but rather that the sympathetic nervous system is selectively stimulated.

Effects of Diazepam Premedication and Epinephrine-Containing Local Anesthetic on Cardiovascular and Plasma Catecholamine Responses to Oral Surgery

The effects of diazepam premedication and administration of an epinephrine-containing local anesthetic on plasma catecholamine levels and cardiovascular parameters were evaluated prior to and during a minor surgical procedure, the removal of impacted third molars. Significant elevations in circulating epinephrine levels (203% above control) and cardiac output (30%) were seen in unsedated patients after administration of lidocaine with epinephrine before surgery, while no changes were seen after lidocaine alone. Unsedated patients had increased norepinephrine (24%) and epinephrine (57%) levels during surgery. Diazepam premedication decreased norepinephrine levels 29% below preoperative levels, followed by an increase during surgery to preoperative levels. These results indicate that intraoral injections of epinephrine-containing local anesthetics result in increased circulating epinephrine levels that are associated with cardiovascular changes and that diazepam premedication decreases plasma norepinephrine levels and attenuates the sympathoadrenal response to surgical stress.

Influence of adrenal epinephrine on postnatal development of tyrosine hydroxylase activity in the superior cervical ganglion.

The effects of bilateral adrenalectomy on postnatal development of tyrosine hydroxylase (TH) activity in the superior cervical ganglion were examined in the rat. Adrenalectomy on day 12 blocked further developmental rise of TH activity, while adrenalectomy on day 7 did not affect normal development of enzyme activity when examined on day 12. The effect of adrenalectomy could be reversed by replacement with daily injections of epinephrine, but not by similar replacement with corticosterone. Chronic administration of SKF 64139, a specific inhibitor of adrenal phenylethanolamine N-methyl-transferase activity that depletes circulating epinephrine levels, also led to a cessation of normal development of TH activity. Similar to adrenalectomy, the effect of SKF 64139 could be observed only after 2 weeks of postnatal development. From these data, it appears that after 2 postnatal weeks, further developmental rise of TH activity in the sympathetic ganglion is an epinephrine-dependent process.

Adrenal influence on tyrosine hydroxylase activity in superior cervical ganglion

The involvement of adrenal hormones as regulatory factors in maintaining physiological levels of tyrosine hydroxylase (TH) was examined in mouse superior cervical ganglion. Following bilateral adrenalectomy, TH activity in the ganglion fell at a slow but steady rate, reaching 60–65% of the control levels after 2 weeks. Decentralization is known also to reduce TH activity in the ganglion. The effects of adrenalectomy and decentralization were therefore compared, and they were found to be additive, indicating different mechanisms in the two cases. The reduction of TH activity following adrenalectomy was not prevented by replacement with corticosterone (0.5 mg/kg, daily). However, replacement with epinephrine (4 mg/kg, daily) completely prevented the fall of TH activity in adrenalectomized animals. Isoproterenol, a β-adrenergic receptor agonist, was as effective as epinephrine in preventing the reduction of TH activity following adrenalectomy. Furthermore, in intact animals, chronic administration of SKF 64139, an inhibitor of adrenal PNMT which depletes circulating epinephrine levels, also reduced ganglionic TH activity to the same level as that after adrenalectomy. These results indicate that epinephrine, but not corticosterone, is the adrenal factor required for physiological maintenance of normal levels of TH in the superior cervical ganglion.

Epinephrine elevation in plasma parallels canine cardiac hypertrophy

Increased circulating epinephrine levels paralled cardiac hypertrophy in response to aortic constriction in the dog. Venous levels of epinephrine were significantly elevated at 24, 48, 72 and 96 hours postcoarctation. There were not significant arterial or venous alterations in norepinephrine levels. Dogs administered propranolol daily had no detectable hypertrophy 96 hours postcoarctation. We suggest that an increased epinephrine level may contribute to the physiological trigger(s) for cardiac hypertrophy.

Effects of physical training in dogs with coronary artery ligation.

This experiment was designed to determine whether physical conditioning can be achieved in the presence of acute myocardial infarction and whether such an exercise program is harmful. For this purpose the effects of a 5-weeks' treadmill-exercise program and inactivity were compared in two groups of dogs in which acute myocardial infarction was produced by coronary artery ligation. The exercised group of animals tolerated the training program well, and neither arrhythmia nor sudden death occurred. At the end of the training program the exercised group of animals displayed the characteristic changes of physical conditioning, namely, reduction in exercise heart rate, cardiac output, and blood lactate levels; rise in circulating epinephrine levels with exercise was also suppressed by conditioning. Postmortem examination revealed neither ventricular dilatation nor aneurysm formation.