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Comparative effects of catecholamines in cardiac tamponade: experimental and clinical studies.

In experimental cardiac tamponade, catecholamines improve hemodynamic variables. To determine whether hemodynamic changes result in increased blood flow to critical organs, tamponade was produced in nine spontaneously breathing, anesthetized dogs. Infusion of dopamine, isoproterenol or norepinephrine doubled cardiac output, but only norepinephrine increased mean arterial pressure. All catecholamines increased blood flow to the myocardium, but not to the brain or kidney. Isoproterenol caused a significant decrease in the endocardial/epicardial blood flow ratio, which was shown to be due to tachycardia. To determine whether catecholamines increase cardiac output and mean arterial pressure in patients with tamponade, eight patients with tamponade due to neoplasms were studied before therapeutic pericardiocentesis. Cardiac output increased only 50 percent with dopamine and isoproterenol and not at all with norepinephrine. Cardiac filling pressure did not decrease with isoproterenol or dopamine, as in experimental tamponade. Only norepinephrine increased mean arterial pressure. Thus, although catecholamines improve hemodynamics in experimental tamponade, the heart is the only critical organ to which blood flow is improved. The hemodynamic benefits of catecholamine administration to patients may be more limited than previous experimental studies have suggested.

Animals↗

Catecholamine physiology in the ovine fetus. I. Gestational age variation in basal plasma concentrations.

Fifty-five ewes with chronically catheterized singleton gestations were studied to assess changes in basal concentrations of fetal catecholamines with increasing gestational age. All pregnancies were time dated, and measurements of catecholamines were conducted at least 5 days after placement of fetal catheters when fetal metabolic parameters had normalized. Plasma concentrations of catecholamines were measured by radioenzymatic assay. Additionally, fetal heart rate (FHR) and corrected mean blood pressure were analyzed in 32 of the fetuses for correlation with plasma levels of catecholamines. Multiple regression analysis revealed significant inverse correlations of fetal plasma concentrations of catecholamines with gestational age, as follows: norepinephrine (p less than 0.001), epinephrine (p less than 0.05), and dopamine (p less than 0.01). FHR correlated inversely with gestational age (p less than 0.001) and positively with circulating levels of norepinephrine (p less than 0.001).

Animals↗

Localized catecholamine storage associated with granules in murine neuroblastoma cells.

Catecholamine storage was examined in cultures of the murine neuroblastoma cell line, N-TD6, using histofluorescence, electron microscopic, isotopic and radioautographic criteria. This line was originally derived from uncloned, C1300 tumor cells by selection in tyrosine deficient medium. N-TD6 cells possess both tyrosine hydroxylase (tyrosine-3-monooxygenase, EC 1.14.16.2) and dopamine beta-hydroxylase (dopamine beta-monooxygenase, EC 1.14.17.1) activities. When examined for paraformaldehyde-induced histofluorescence, a small percentage of cells in the population show intense catecholamine fluorescence, often localized within discrete regions of the cellular processes. Electron microscopic examination of these cells reveals both electron lucent vesicles and more frequent, electron dense granules, 50-70 nm and 100-300 nm in diameter, respectively. The distribution of these granules and vesicles varies, but they appear most numerous near the cell surface, along processes and within process endings. By labeling cells with [3H]dopamine and then allowing the cells to release unbound label in the presence of unlabeled dopamine, the localization of catecholamine stores was visualized by radioautographic techniques. While a variety of intracellular distribution of radioactivity were observed, the most prominent concentrations were found in the processes and their terminals; no labeled material was retained when reserpine was present during uptake. The topographic coincidence of granules, catecholamine fluorescence and [3H]dopamine retention in these neuroblastoma cells suggests that catecholamines are stored within these granules in a manner analogous to that observed in normal adrenergic neurons.

Animals↗

Inhibition by omega-conotoxin GVIA of adrenal catecholamine release in response to endogenous and exogenous acetylcholine.

Effects of the N-type voltage-dependent Ca2+ channel (VDCC) blocker, omega-conotoxin GVIA, and the L-type VDCC blockers, nifedipine and verapamil, on adrenal catecholamine release were examined in anesthetized dogs. These blockers were infused into the adrenal gland through the phrenicoabdominal artery. Splanchnic nerve stimulation at 1 and 3 Hz produced frequency-dependent increases in epinephrine and norepinephrine output determined from adrenal venous blood. Infusion of omega-conotoxin GVIA (0.4 micrograms/min) significantly inhibited the splanchnic nerve stimulation-evoked increases in epinephrine and norepinephrine output. Furthermore, increases in epinephrine and norepinephrine output induced by intraarterial injection of acetylcholine (3 micrograms) into the adrenal gland also were inhibited by omega-conotoxin GVIA (0.4 micrograms/min). Further inhibition of splanchnic nerve stimulation- or exogenous acetylcholine-induced increases in catecholamine output was observed even after the cessation of omega-conotoxin GVIA infusion. Neither nifedipine (1 microgram/min) nor verapamil (10 micrograms/min) affected the splanchnic nerve stimulation-evoked increases in catecholamine output, whereas they inhibited the exogenous acetylcholine-evoked catecholamine release. These results suggest that N-type VDCCs located in adrenal medullary cells may contribute to the release of adrenal catecholamines in response to endogenous and exogenous acetylcholine in the dog.

Acetylcholine↗

The effect of anoxic submergence and recovery on circulating levels of catecholamines and corticosterone in the turtle, Chrysemys picta.

The ability of some freshwater turtles to tolerate prolonged anoxia is well known. The role of hormones in the regulation of the metabolic adjustments that occur during anoxia, however, is unknown. This study examined the changes in plasma glucose, lactate, catecholamine, and corticosterone levels during submergence anoxia and recovery at 22 degrees C in the painted turtle, Chrysemys picta. Plasma catecholamine levels increased greatly during anoxia, while corticosterone levels decreased. During recovery from anoxia, plasma catecholamine levels fell rapidly while corticosterone levels increased 10-fold over controls. The results are consistent with a role for the catecholamines and corticosterone in the regulation of glucose metabolism in the turtle during anoxia and recovery, respectively. We hypothesize that the catecholamines function to stimulate hepatic glycogenolysis during anoxia and thereby increase plasma glucose levels. Corticosterone may function in the recovery from anoxia by enhancing the resynthesis of liver glycogen from lactate.

Analysis of Variance↗

Adrenal enkephalin and catecholamine contents following subarachnoid hemorrhage in cats.

A "closed space" subarachnoid hemorrhage (SAH) was produced experimentally in cats by rupture of the right middle cerebral artery to test the working hypothesis that a stressful event which provokes powerful sympathoadrenal discharge: causes a massive release of co-stored endogenous enkephalins together with catecholamines, induces an increased rate of opioid peptide precursor processing and/or synthesis, and eventually results in markedly elevated tissue levels of enkephalins relative to controls and to co-stored catecholamines. Adrenal medulla and other tissues were analyzed for met- and leu-enkephalins by RIAs and norepinephrine and epinephrine by HPLC-EC at 4 hrs, 3, 10, 16 and 30 days post-SAH. Catecholamines of adrenal medulla were already decreased at 4 hrs and by 3 days post-SAH depletion of epinephrine reached 86% and norepinephrine 53% compared to controls. Concurrently, at 4 hrs and 3 days post-SAH, the adrenal medulla was depleted 47% of met- and 53% of leu-enkephalins. By 10 days post-SAH, when catecholamines had regained control levels, met-enkephalin was elevated to 240% of control and 435% compared to the 3 day depletion; it remained elevated through 30 days post-SAH. In comparison, after 10 days reserpine treatment when catecholamines were markedly depleted, met-enkephalin rose to 970% and leu-enkephalin to 360% relative to controls, confirming recent reports in the literature. The data suggest that release of enkephalins originates primarily from epinephrine-type cells of the adrenal medulla in cat.

Adrenal Medulla↗

High-performance liquid chromatographic analysis of catecholamines in biological samples by liquid/liquid extraction prepurification.

A prepurification procedure for the determination of catecholamines in biological samples was studied to simplify the procedure and increase selectivity and recovery. The procedure is based on liquid/liquid extraction of catecholamine-borate complexes. Under optimal conditions, catecholamines formed complexes with diphenylborate in an alkaline NH4Cl/NH4OH buffer that were extracted with n-heptanol. Catecholamines were reextracted into an HCl-acidified solution, followed by reversed-phase ion-pair high-performance liquid chromatographic separation with fluorometric detection. Application of the method to various samples of rat tissues and human urine showed procedural simplicity, high selectivity, and high recovery (about 90% or more for tissue samples). This method can be used for pharmacological studies on catecholamines.

Adult↗

Effect of alpha-bungarotoxin and etorphine on acetylcholine-evoked release of endogenous and radiolabeled catecholamines from primary culture of adrenal chromaffin cells.

Cell cultures of adrenal medulla have become an important research tool to study basic processes that regulate catecholamine storage, release and synthesis. Release has been studied either by labeling with [3H]norepinephrine and measuring release of radioactivity or by measuring the endogenous catecholamines released with HPLC. Acetylcholine (5 X 10(-6)-10(-4) M) appears to release preferentially norepinephrine, although the cells store more epinephrine than norepinephrine. Etorphine and alpha-bungarotoxin antagonize the release of catecholamines elicited by acetylcholine. This inhibitory action appears to be greater when the measurement of endogenous catecholamines rather than radioactive norepinephrine is used to monitor the action of acetylcholine. The data suggest that the measurement of endogenous catecholamines by HPLC is preferable to the [3H]NE loading and release technique, especially when analyzing the effects of low concentrations of drugs that are thought to affect nicotinic receptor function.

Acetylcholine↗

Intra-adrenal interactions in fish: catecholamine stimulated cortisol release in sea bass (Dicentrarchus labrax L.).

The effect of the catecholamines, adrenaline and noradrenaline, on sea bass (Dicentrarchus labrax) and sea bream (Sparus auratus) interrenal cortisol production was studied in vitro using a dynamic superfusion system technique. Increasing concentrations of catecholamines (10(-6), 10(-8) and 10(-10) M) stimulated cortisol production in a dose-dependent manner, in sea bass only. The increase in cortisol production stimulated by adrenaline (10(-6) M) and noradrenaline (10(-6) M) was inhibited by sotalol (2 x 10(-5) M), but not by prazosin suggesting that catecholamines stimulate cortisol release through the beta-receptor subtype. To evaluate catecholamine-induced signal transduction in head kidney cells, measurements of cAMP production and [H3]myo-inositol incorporation were determined in head kidney cell suspensions. Adrenaline and noradrenaline (10(-6) M) increased cAMP production, but had no effect on total inositol phosphate accumulation. These results indicate that catecholamines released from the chromaffin cells within the interrenal tissue may act as a paracrine factor to stimulate interrenal steroidogenesis in the sea bass.

Adrenergic alpha-Antagonists↗

Simultaneous determination of catecholamines and polyamines in PC-12 cell extracts by micellar electrokinetic capillary chromatography with ultraviolet absorbance detection.

A method for simultaneous determination of polyamines and catecholamines in cell extracts by micellar electrokinetic capillary chromatography with UV detection at 254 nm was established at the first time. The polyamines (putrescine, spermidine and spermine) and catecholamines (dopamine, serotonin, norepinephrine and epinephrine) were extracted from PC-12 cells and were derivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Different derivatization conditions such as temperature, ratio of derivatization reagents and incubation time were investigated to find the best reaction condition which gave the highest detection sensitivity for polyamines and catecholamines. The influence of running buffer and additives on the separation such as pH, sodium dodecyl sulfate (SDS) concentrations and various additives was also investigated. Separation was achieved within 20 min with good repeatability in a 100mM boric acid buffer containing 10mM SDS and 10mM 18-crown-6 at a pH of 9.5. The detection limit ranged from 1.0 x 10(-7) to 9.0 x 10(-7) M, which is sufficient for determination of polyamines and catecholamines in many cell extracts. This technique can be easily applied to polyamine-related anticancer drug studies or clinical follow-ups after each dosage of these anticancer drugs, since these drugs not only have great inhibition on polyamine levels in blood, but also have a large influence on catecholamine levels in blood.

Animals↗

Do catecholamines directly modulate the delayed plateau potassium current in frog atrium?

An important electrophysiological action of catecholamines in the heart is the modulation of the second inward current (iCa). Catecholamine augmentation of iCa has been attributed to an increase in the number of functional channels, as well as an increase in the probability of channel opening [1, 4, 12]. Another important electrophysiological action of catecholamines in the heart is the modulation of time-dependent outward currents. In the Purkinje fibre, epinephrine has been shown to shift the voltage-dependence of the pacemaker current, iK2 [13]. The delayed outward current(s) which is activated over the plateau range of potentials (ix) is also augmented by catecholamines in Purkinje fibers [14] as well as frog atrium [3]. Several possible mechanisms for enhancement of the outward plateau current by catecholamines have been proposed [2]: (i) a direct increase in the maximal conductance of the channel; (ii) an indirect enhancement of outward current mediated by stimulation of Na+-K+ exchange (which may reduce potassium concentration in restricted extracellular spaces and hence produce an increase in the driving force for K+) or (iii) an indirect augmentation of outward current via enhancement of intracellular Ca2+ (calcium-activated potassium conductance) [10]. To distinguish between these possible mechanisms, the influence of epinephrine and isoproterenol on the delayed outward K+ current in single isolated bullfrog atrial cells was examined. Evidence is presented that in single frog atrial cells, concentrations of epinephrine or isoproterenol which produce large increases in the second inward current have no detectable effect upon the delayed plateau K+ current.

Animals↗

Catecholamines and lipopolysaccharide synergistically induce the release of interleukin-6 from thymic epithelial cells.

The thymus as the major site of T-cell development is exposed to circulating hormones as well as to neurotransmitters released from peripheral nerves. We investigated the influence of catecholamines on the synthesis of interleukin-1 (IL-1) and IL-6 by cultured rat thymic epithelial cells. Basal or lipopolysaccharide (LPS)-stimulated production of IL-1 was not affected by catecholamines. Release of IL-6 was stimulated only scarcely by catecholamines or tumor necrosis factor-alpha (TNF-alpha) and moderately by LPS alone. However, co-stimulation with adrenaline, noradrenaline, or the beta-adrenoceptor agonist isoproterenol (isoprenaline) had an additive (TNF-alpha) or synergistic (LPS) effect on IL-6 release. The synergistic effect was dose-dependent on catecholamine or LPS concentrations. It was mediated by beta-adrenoceptors that are linked to elevation of intracellular cAMP levels, since it was promoted by beta-adrenoceptor agonists and could be blocked by beta-adrenoceptor antagonists. Co-incubation of LPS with agents directly raising cAMP-levels like forskolin or dibutyryl cAMP yielded even stronger IL-6 induction. After co-stimulation IL-6 mRNA was first detected after 3-4 h and a constant increase of IL-6 bioactivity in the culture supernatant was measured for up to 48 h. Since IL-6 is an important factor for thymocyte differentiation and proliferation, the findings demonstrate an influence of neuronal or hormonal catecholamines on the thymic microenvironment that is created by thymic epithelial cells.

Adrenergic alpha-Agonists↗

Role of different subtypes of adrenoceptors in pressor responses to catecholamines released from sympathetic nerve endings.

The role of alpha 1- and alpha 2-adrenoceptors in the vascular effects of catecholamines, either released locally from sympathetic nerve endings (e.g., in vascular smooth muscle) or derived from the adrenal medulla or administered intravenously, was studied using selective antagonists of these adrenoceptors. The ganglionic stimulant dimethylphenyl-piperazinium-iodide (DMPP) exerted dual actions on blood pressure: a rapid and short-term pressor reaction (phase I) resulting from catecholamine release elicited by ganglion stimulation, followed by a more sustained blood pressure elevation (phase II) resulting from the circulating catecholamines released from the adrenal medulla. The selective alpha 2-adrenoceptor, but a not subtype selective, antagonist 7,8-(methylenedioxi)-14-alpha-alloberbane HCl (CH-38083) (50-100 micrograms/kg, IV) significantly (p < 0.05) inhibited the pressor effects of epinephrine and norepinephrine given intravenously and phase II of the DMPP-induced pressor reaction. Idazoxan exerted similar effects, but at higher doses (400-600 micrograms/kg, IV). WB-4101 (50-100 micrograms/kg, IV) and BRL-44408 (2-3 mg/kg, IV), two selective alpha 2A-adrenoceptor antagonists, had the same activity as CH-38083, except did not inhibit the pressor effect of intravenously administered norepinephrine. The alpha 2B-adrenoceptor selective antagonist, ARC-239 (150 micrograms/kg, IV) did not influence phase II of DMPP-induced pressor reaction. Prazosin (200 micrograms/kg, IV), an antagonist of alpha 1 and alpha 2B-adrenoceptors, reduced blood pressure, the pressor response to intravenously administered epinephrine, and phase I of the DMPP-induced pressor effect. In addition, it completely inhibited the pressor responses to DMPP remaining after administration of CH-38083. These results suggest that the postsynaptically located alpha 1- and alpha 2(A and B)-adrenoceptors are involved in pressor response to norepinephrine and epinephrine, and are sensitive and accessible to catecholamines released locally from the axon terminals, and from the circulation to a different extent. These results may have great therapeutical importance in hypertension, for which the involvement of both a high level of circulating and locally released catecholamines may be indicative of the usefullness of a combination (alpha 1- and alpha 2-adrenoceptors- and Ca-channel-blocking agents) therapy.

Adrenergic alpha-Antagonists↗

Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP).

We studied the effects of chronic nocturnal hypoxaemia due to obstructive sleep apnoea syndrome (OSAS) on the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-testicular axes and on catecholamine and cortisol secretion. We investigated whether hormones other than catecholamines may serve as markers for chronic hypoxic stress and the possible effects of nasal continuous positive airway pressure (nCPAP) treatment on endocrine status. Nocturnal oximetry was performed in 16 male patients with OSAS diagnosed by polysomnography, immediately before nCPAP treatment and in 11 of the patients the oximetry was repeated after 7 months of nCPAP therapy. Plasma and urinary catecholamines, luteinizing hormone (LH) testosterone, cortisol, thyroid stimulating hormone (TSH), prolactin (PRL), and the response of TSH and PRL to a thyroid releasing hormone (TRH) challenge test were measured immediately before and after 7 months of nCPAP treatment. Subnormal LH and TSH and elevated serum cortisol as well as increased nocturnal urinary norepinephrine levels were found in patients prior to treatment; otherwise endocrine values were normal. There was a significant correlation between low pretreatment nocturnal arterial oxygen saturation and high plasma and urinary norepinephrine levels. The nCPAP treatment caused significant reduction in serum prolactin and TSH, and significant reduction in plasma epinephrine and urinary norepinephrine. The reduction in serum TSH and urinary norepinephrine was most pronounced in the subjects with the worst pretreatment nocturnal hypoxaemia. No other significant changes were found in basal hormone levels. The response to TRH challenge was normal before and after treatment and was not influenced by CPAP therapy. OSAS is associated with elevated catecholamine and cortisol and decreased TSH and LH levels but a normal response to TRH challenge and a normal androgen status. Apart from catecholamines, none of the hormones studied is likely to serve as a specific marker for chronic hypoxic stress.

Adult↗

Ca2+-stimulated catecholamine release from alpha-toxin-permeabilized PC12 cells: biochemical evidence for exocytosis and its modulation by protein kinase C and G proteins.

Two possible cellular pathways of catecholamines from the chromaffin vesicles of PC12 cells to the surrounding medium are explored in this study. The direct one circumventing the cytoplasm can be activated in alpha-toxin-permeabilized cells with micromolar levels of free Ca2+. Catecholamine metabolites formed in the cytoplasm (i.e., 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylethanol) are neither formed nor released from the cells under these conditions. However, when vesicular catecholamines were discharged into the cytoplasm by addition of the ionophore nigericin, such metabolites are formed and released into the medium independent of Ca2+. Both types of experiments provide direct evidence for the operation of Ca2+-induced exocytosis of dopamine and noradrenaline in permeabilized PC12 cells. The Ca2+ dependence of dopamine or noradrenaline release, as measured by the determination of the endogenous catecholamines using the high-performance liquid chromatography technique, exhibits two different phases. One is already activated below 1 microM free Ca2+ and plateaus at 1-5 microM free Ca2+, while a second occurs in the presence of larger amounts of free Ca2+ (10-100 microM). Ca2+-induced catecholamine release from the permeabilized cells can be modulated in different ways: It is enhanced by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate and the diacylglycerol 1-oleyl-2-acetylglycerol provided Mg2+/ATP is present, and it is inhibited by guanosine 5'-O-(3-thiotriphosphate). The latter effect is abolished by pretreatment of the cells with pertussis toxin but not by cholera toxin. Thus, it appears that Ca2+-induced exocytosis can be modulated via the protein kinase C system, as well as via GTP binding proteins.

Adrenal Gland Neoplasms↗

Dopa, catecholamines and their metabolites in essential hypertension.

1. Urinary excretion of dopa, catecholamines and their metabolites (vanillylmandelic acid, methoxycatecholamines, 3-methoxy-4-hydroxyphenylglycol and homovanillic acid) were studied in eighty patients with essential hypertension and in twenty-five healthy control subjects. 2. Increased urinary excretion of catecholamines, dopa and catecholamine metabolites was found in a proportion of cases. 3. The relationship between urinary excretion of catecholamine metabolites and the excretion of dopa and noradrenaline was studied. 4. In view of the suggested significance of 3-methoxy-4-hydroxyphenylglycol as an index of brain catecholamine metabolism, particular attention was paid to urinary excretion of this metabolite in the subjects under study.

Adult↗

Insulin-like growth factors decrease catecholamine content in PC12 rat pheochromocytoma cells.

Insulin-like growth factors (IGFs) stimulate proliferation and differentiation of PC12 rat pheochromocytoma cells and modulate catecholamine release in bovine adrenal medullary cells. Dexamethasone increases catecholamine synthesis in PC12 cells. We therefore studied the effects of IGFs and dexamethasone on catecholamine content in PC12 cells. Dopamine (DA) and norepinephrine (NE) content of PC12 cells were measured after incubation for 72 h with IGFs (100 ng/ml) and/or dexamethasone (500 nM). IGF-I (100 ng/ml) and IGF-II (100 ng/ml) decreased DA and NE content to approximately 35% and approximately 25% of control, respectively. [Leu27]IGF-II, which binds to the IGF-I receptor with markedly decreased affinity, did not reduce catecholamine levels, indicating that the effect is likely to be mediated by the IGF-I receptor. Dexamethasone (500 nM) increased levels of DA and NE to 173 +/- 20% and 331 +/- 48% of controls, respectively. Coincubation with IGFs did not significantly affect the stimulation of DA by dexamethasone, but abolished the rise in NE. Levels of tyrosine hydroxylase mRNA, protein and activity were increased following incubation with dexamethasone, but were unchanged by IGFs. These results indicate that IGFs decrease catecholamine content in PC12 cells via the IGF-I receptor. Complex regulation involving multiple synthetic and/or degradative steps is implicated in this process.

Animals↗

Early effects of total hepatectomy on haemodynamic state and organ uptake of catecholamines in the pig.

In a previous study, we showed that plasma concentrations of catecholamines were increased during the anhepatic phase in pigs. In this study, we investigated if a constant depth of anaesthesia would prevent these changes and, if not, if the changes were caused by impaired extraction of catecholamines. We measured arterial and venous pressures, heart rate and cardiac output in 10 anaesthetized pigs. Hepatic arterial and portal venous flows were measured. Blood for measurement of catecholamines was sampled from carotid and pulmonary arteries and portal, hepatic and renal veins. After a 2-h observation period, the liver was removed and the circulation reconstituted. Measurements were made and samples obtained for another 2 h. Catecholamine concentrations increased 2-10-fold after hepatectomy. Before hepatectomy, noradrenaline was extracted by the lung (mean extraction ratio 23 (SEM 8)%) and the liver (30 (11)%); after hepatectomy, there was extraction by the kidney (24 (12)%) but extraction by the lung (29 (8)%) was unchanged. Before hepatectomy, adrenaline was extracted predominantly by the kidney (73 (5)%) and the liver (70 (6)%), with minimal extraction by the lung; after hepatectomy, extraction by the lung increased (25 (4)%) and decreased slightly in the kidney (56 (6)%). While mean arterial pressure did not change, heart rate increased by approximately 50% and cardiac index declined (ns) within 2 h after hepatectomy. There was a sharp increase in pulmonary vascular resistance after removal of the liver and changes correlated with increases in arterial plasma concentrations of catecholamines.

Anesthesia, General↗