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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 127 records · Page 7Linked to original sources

Detection of histamine-induced capillary protein leakage and hypovolaemia by determination of indocyanine green and glucose dilution method in dogs.

OBJECTIVE: The plasma volume of histamine-induced protein capillary leakage may be overestimated when this is determined using the indocyanine green (ICG) dilution method (Vd-ICG), since this dye binds to plasma proteins. The initial distribution volume of glucose (IDVG) has been shown to indicate the central extracellular fluid volume including plasma. Accordingly, the overestimation would be detected by a higher Vd-ICG/IDVG ratio. Our study was intended to examine whether the simultaneous measurement of these two variables can evaluate histamine-induced protein leakage and associated hypovolaemia. DESIGN: Prospective animal study. SETTING: Institutional animal research laboratory. SUBJECTS: Twenty-four anaesthetized and ventilated mongrel dogs. INTERVENTIONS: Anaesthetized animals were mechanically ventilated and received infusions of normal saline (n = 8), histamine 50 microg/kg per h (n = 8), or histamine 100 microg/kg per h. The Vd-ICG and IDVG were calculated using a one-compartment model by simultaneous administration of ICG 0.5 mg/kg, and glucose 100 mg/kg followed by serial arterial blood sampling. MEASUREMENTS AND RESULTS: In both histamine groups, a significant elevation of haematocrit and a decrease of plasma albumin concentration were found (p<0.05). Although the IDVG decreased following histamine administration (p<0.05), the Vd-ICG remained unchanged. The Vd-ICG/IDVG ratio increased in a dose-dependent manner after histamine administration (p<0.05), but remained unchanged following normal saline administration. CONCLUSION: The results suggest that the Vd-ICG/IDVG ratio and the IDVG are useful in evaluating the magnitude of the leakage and hypovolaemia.

Animals↗

Does indocyanine green accurately measure plasma volume independently of its disappearance rate from plasma in critically ill patients?

OBJECTIVE: To determine whether plasma volume determined by the indocyanine green (ICG) dilution method (PV-ICG) is equally accurate independently of its disappearance rate from plasma in the critically ill. DESIGN: Retrospective clinical investigation. SETTING: Intensive care unit of a university teaching hospital. PATIENTS AND METHODS: 192 adult patients were initially enrolled. The PV-ICG and the initial distribution volume of glucose (IDVG) were calculated utilizing a one-compartment model by simultaneous administration of ICG 25 mg and glucose 5 g on the first day of measurement in each patient. Twenty-one patients were excluded from the study because of a higher PV-ICG/IDVG ratio (> 0.45) indicating apparent overestimation of the PV-ICG associated with the generalized protein capillary leakage. The remaining 171 patients were divided into four groups according to the magnitude of their disappearance rate of ICG from plasma (Ke-ICG). RESULTS: Convergence was assumed consistently in each ICG or glucose decay curve, even in the lower Ke-ICG less than 0.10/min. The relationship between the two volumes was not statistically different among groups. CONCLUSIONS: The results suggest that the measurement of the PV-ICG can be equally accurate independently of its disappearance rate from plasma unless there is generalized protein capillary leakage.

APACHE↗

No psychological emergence reactions in schizophrenic surgical patients immediately after propofol, fentanyl, and ketamine intravenous anesthesia.

PURPOSE: We attempted to determine the frequency of adverse psychological events after total intravenous anesthesia with propofol-fentanyl-ketamine (PFK) in surgical schizophrenic patients. METHODS: PFK was used in 25 schizophrenic patients undergoing various surgical procedures from 1995 to 1997. Adverse events occurring during and after anesthesia were recorded. Psychiatric follow-up was also done during the first 3 postoperative weeks at least. RESULTS: One patient died postoperatively of airway obstruction from concomitant severe malignant thyroid disease, but in the remaining patients neither respiratory nor cardiovascular states during or after anesthesia became unstable. None of the patients developed adverse psychological emergence reactions immediately after anesthesia. Two patients undergoing major surgical procedures exhibited delirium in the early postoperative days despite taking their routine antipsychotic drugs postoperatively. CONCLUSIONS: We suggest that PFK maintains stable respiratory and cardiovascular states, and causes no psychological emergence reactions in schizophrenic surgical patients. However, adverse psychological events may occur postoperatively, probably due to continued psychic stress. We therefore recommend appropriate perioperative management and further psychological studies for such patients.

Journal Article↗

Overexpression of insulin-like growth factor-1 (IGF-I) receptor and the invasiveness of cultured keloid fibroblasts.

Keloid is a dermal fibroproliferative tissue of unknown etiology. Protein tyrosine kinases (PTKs) play an important role in the regulation of cell growth and differentiation. Activation of PTK cascades in keloid fibroblasts is thought to be closely linked to abnormal cell proliferation and migration. We determined the expression profile of PTK genes in normal skin and keloid fibroblasts using the homology cloning method with a degenerated primer. Eight PTK genes were expressed among a total of 46 receptor-type clones. The most abundant type of PTK receptors was the platelet-derived growth factor receptor in both fibroblasts. However, insulin-like growth factor-I receptor (IGF-IR) was overexpressed only in keloid-derived fibroblasts (9 of 24). Immunohistochemical analysis confirmed the high expression of IGF-IR in keloid fibroblasts, but not in normal fibroblasts. To examine the functional properties of the IGF-I/IGF-IR pathway, we investigated cell proliferation and invasion activities of both types of fibroblasts. The mitogenic effect of IGF-I on both fibroblasts was very weak compared with serum stimulation. In contrast, the invasive activity of keloid fibroblasts was markedly increased in the presence of IGF-I, and inhibited by a neutralizing antibody against IGF-IR. Our results indicate the involvement of activated IGF-I/IGF-IR in the pathogenesis of keloid by enhancing the invasive activity of fibroblasts.

Adolescent↗

Intracellular signalling pathways of okadaic acid leading to mitogenesis in Rat1 fibroblast overexpressing insulin receptors: okadaic acid regulates Shc phosphorylation by mechanisms independent of insulin.

Okadaic acid is a powerful inhibitor of serine/threonine protein phosphatases 1 and 2A. Although it is known as a potent tumour promoter, the intracellular mechanism by which okadaic acid mediates its mitogenic effect remains to be clarified. We investigated the effect of okadaic acid on the activation of mitogenesis in Rat1 fibroblasts overexpressing insulin receptors. As previously reported, insulin induced Shc phosphorylation, Shc-Grb2 association, MAP kinase activation, and BrdU incorporation. Okadaic acid also stimulated tyrosine phosphorylation of Shc and its subsequent association with Grb2 in a time- and dose-dependent manner without affecting tyrosine phosphorylation of insulin receptor beta-subunit and IRS. However, to a lesser extent, okadaic acid stimulated MAP kinase activity and BrdU incorporation. Interestingly, preincubation of okadaic acid potentiated insulin stimulation of tyrosine phosphorylation of Shc (213% of control), Shc-Grb2 association (150%), MAP kinase activity (152%), and BrdU incorporation (148%). These results further confirmed the important role of Shc, but not IRS, in cell cycle progression in Rat1 fibroblasts. Furthermore, serine/ threonine phosphorylation appears to be involved in the regulation of Shc tyrosine phosphorylation leading to mitogenesis by mechanisms independent of insulin signalling.

Adaptor Proteins, Signal Transducing↗

1,3-Selenazine derivatives induce cytotoxicity and DNA fragmentation in human HT-1080 fibrosarcoma cells.

The inhibitory effects of a series of 5,6-dihydro-4H-1,3-selenazine derivatives, 1,3-selenazole, and 5,6-dihydro-4H-1,3-thiazine derivatives on the proliferation of human HT-1080 fibrosarcoma cells were investigated. The compounds 4-ethyl-4-hydroxy-2-p-tolyl-5, 6-dihydro-4H-1,3-selenazine (TS-2) and 4-hydroxy-4-methyl-6-propyl-2-p-tolyl-5,6-dihydro-4H-1,3-selenazine++ + (TS-6) exhibited the strongest inhibitory effect among 1, 3-selenazine derivatives, and the EC(50) of TS-2 and TS-6 was 7.76 and 8.40 microM, respectively. On the other hand, 1,3-selenazole and 5,6-dihydro-4H-1,3-thiazines had no inhibitory effects. TS-2 and TS-6 inhibited the proliferation of HT-1080 cells time- and dose-dependently. They induced dose-dependent DNA fragmentation in HT-1080 cells, revealing a typical apoptosis characteristics. The present study demonstrated that TS-2 and TS-6 inhibited HT-1080 proliferation through the induction of DNA fragmentation.

Apoptosis↗

Renin-aldosterone system and atrial natriuretic peptide during anesthesia in orthopedic patients over 80 years of age.

STUDY OBJECTIVES: To investigate the changes in plasma atrial natriuretic peptide, renin activity, and aldosterone during isoflurane anesthesia in patients over 80 years. DESIGN: Prospective, randomized, controlled study. SETTING: Operating rooms and postanesthesia recovery room of Hirosaki University Hospital and Hakodate Watanabe Hospital. PATIENTS: 36 patients undergoing reduction of femur neck fracture (18 patients ranging in age from 80 to 99 years and 18 patients ranging in age from 40 to 59 years as control). INTERVENTION: In all patients, anesthesia was induced with intravenous (i.v.) thiopental sodium 3 to 5 mg/kg succinylcholine 0.5 to 1.0 mg/kg for facilitating tracheal intubation and was maintained with 1.2% to 2.0% isoflurane in 50% oxygen. MEASUREMENTS AND MAIN RESULTS: Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA), and plasma aldosterone (PA) levels were assayed. Blood samples were obtained on the following occasions: before the induction of anesthesia, 15 minutes after skin incision, 90 minutes after anesthesia induction, and the 60 minutes after the end of surgery. Plasma renin activity and PA levels in patients from 40 to 59 years increased significantly 90 minutes after induction, whereas PRA and PA levels in patients over 80 years were unchanged. There were significant differences in PRA and PA levels between both groups at any time of measurements. Plasma ANP levels of patients over 80 years were significantly elevated at 90 minutes induction. Plasma ANP levels in patients over 80 years at 90 minutes after the induction and 60 minutes after the end of surgery were significantly higher than those of patients from 40 to 59 years. Plasma renin activity in hypertensive patients over 80 years at 90 minutes after the induction was significantly lower than that observed in normotensive patients. The renal loss of sodium was increased in the hypertensive patients. CONCLUSIONS: Orthopedic patients over 80 years of age have decreased PRA and PA, increased ANP, and renal loss of sodium as compared with patients 40 to 59 years, during isoflurane anesthesia. Plasma renin activity at 90 minutes after induction was decreased in hypertensive patients over 80 years, but PA and ANP were not affected by hypertension during anesthesia.

Adult↗

Evaluation of erectile response by continuous measurement of penile diameter in rats.

The present study was performed to determine whether measurement of penile diameter in an in vivo rat model is useful for pharmacologic and physiologic investigations on penile erection. Penile erection induced by electrical stimulation of the cavernous nerve was monitored by measuring the penile diameter sonomicrometrically with a pair of 10-MHz piezoelectric crystals glued to the opposite surfaces of the adventitia of the penile erectile chamber in anesthetized rats. Using this method, we examined the effects of a nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), and a well-known phosphodiesterase 5 (PDE5) inhibitor, zaprinast, on the maximal developed penile diameter (D-max) and the time from the maximum response to 50% recovery (T50%) of the maximum response as an index of the duration of penile erection. An intravenous injection of L-NAME at a dose of 10 mg/kg significantly inhibited D-max produced by cavernous electrical stimulation at 5 to 50 V, without affecting T50%. Sequential intravenous infusions of 10, 30, 100, and 300 microg/kg/min of zaprinast at 30-min intervals did not show any effect on D-max, heart rate, and systolic arterial pressure, although doses of 100 and 300 microg/kg/min significantly prolonged T50% and the maximum dose decreased diastolic arterial pressure. Moreover, zaprinast produced a more prominent increase in cyclic guanosine monophosphate (cGMP) levels than cyclic adenosine monophosphate levels in the plasma taken at the end of the maximum dose infusion. Measurement of murine penile diameter with a sonomicrometrical device, indicating that a NO-cGMP-PDE5 pathway plays a pivotal role in the penile diameter increase and its maintenance, would be useful for pharmacologic and physiologic investigations on penile erection.

Animals↗

Is total body weight an appropriate predictor for propofol maintenance dose?

BACKGROUND: Infusion rate of propofol during anaesthesia is usually based on total body weight. In this study, we have determined the relationship between total body weight and plasma propofol levels when the infusion rate was based on total body weight. METHODS: Sixty patients undergoing elective surgery were studied. Anaesthesia was induced with propofol 1 mg x kg(-1), ketamine 1 mg x kg(-1) and fentanyl 2 microg x kg(-1), and maintained with propofol 5 mg x kg(-1) x h(-1), ketamine 0.5-1 mg x kg(1) x h(-1) and fentanyl 5-15 microg x kg(-1). Propofol infusion rate did not change during anaesthesia, and infusion was terminated at the end of surgery. Immediately prior to termination of the propofol infusion, arterial blood (5 ml) was collected to measure plasma level of propofol by a high-performance liquid chromatography equipped with electrochemical detection. RESULTS: There was a significant correlation between plasma propofol and total body weight (r=0.646, P<0.001). Plasma propofol concentration also correlated with infusion rate, corrected to lean body mass (r=0.527, P<0.001). CONCLUSION: During a fixed infusion rate, plasma propofol concentration may be dependent on total body weight.

Anesthetics, Dissociative↗

Estimation of the initial distribution volume of glucose by an incremental plasma glucose level at 3 min after i.v. glucose in humans.

AIMS: The initial distribution volume of glucose (IDVG) could be a clinically useful indicator of the central extracellular fluid (ECF) space volume, namely the interstitial fluid volume status of highly perfused organs. In this study, we determined the formula of IDVG using incremental plasma glucose levels after i.v. glucose. METHODS: One hundred and fifty patients admitted to the general intensive care unit of the University of Hirosaki hospital were entered into this prospective study which was conducted in two stages. In the first stage 300 data points from 100 patients were used to measure the IDVG (3 determinations for each patients). This utilized a one compartment model to describe the incremental plasma glucose decay curve following an intravenous bolus injection of glucose which, in turn, was used to derive the parameters of an equation for IDVG prediction following a single plasma sample. The second stage was a validation of the equation using a separate data set (150 points) from a further 50 patients. RESULTS: A one phase exponential decay model was well-fitted for the IDVG-postadministration glucose level curve, and indicated that the incremental glucose level at 3 min after i.v. glucose was best-correlated to the IDVG compared with those at 1, 2, 4, 5 and 7 min postadministration. The formula of the IDVG was obtained from the curve: IDVG=24.44xe-0.0298xDeltaGL+2.70, where DeltaGL=incremental glucose level at 3 min after i.v. glucose. Another 150 samples showed that the measured-IDVG from a one compartment model and predicted-IDVG from the formula were 7.24+/-1. 63 and 7.27+/-1.52 l, respectively, and that there was a significant correlation between the two IDVGs (r=0.966, P<0.0001). CONCLUSIONS: Using an incremental glucose level at 3 min after i.v. glucose, we have established the reliable formula for determination of the IDVG which could be a clinically useful indicator of the central ECF volume.

Blood Glucose↗

Renin-aldosterone in elderly patients with hyperkalaemia under anaesthesia.

Elderly patients with hyperkalaemia often have low concentrations of plasma renin and aldosterone, perhaps secondary to reduced glomerular filtration and sympathetic insufficiency. The endocrine response to surgical stress and volume expansion during anaesthesia was studied in seven elderly patients with hyperkalaemia (mean age 87.7 +/- SD 5.3 years), 18 elderly patients without hyperkalaemia (86.5 +/- 5.5 years), and 18 younger patients (52.6 +/- 7.2 years) as controls. Base-line values, in hyperkalaemic elderly patients, for plasma renin activity and plasma aldosterone concentration were 0.8 +/- 0.3 ng mL-1 h-1 and 2.8 +/- 0.8 pg mL-1 respectively (significantly lower than in the younger patients), and 287 +/- 42 pg mL-1 for plasma atrial natriuretic peptide levels, which were significantly higher. The plasma renin activity and aldosterone concentrations in elderly patients with hyperkalaemia were at all times lower, but not significantly, than those of the elderly patients without hyperkalaemia. The atrial natriuretic peptide concentrations (351 +/- 48 pg mL-1) in the hyperkalaemic elderly were significantly higher 90 min after induction of anaesthesia than in the normokalaemic elderly (108 +/- 38 pg mL-1). Hormone concentrations in the hyperkalaemic patients did not change during anaesthesia, but plasma atrial natriuretic peptide concentrations increased significantly in the normokalaemic elderly, and plasma renin activity and aldosterone of the younger patients increased significantly during anaesthesia. These results indicate that plasma renin activity, and the concentrations of aldosterone and of atrial natriuretic peptide in elderly patients with hyperkalaemia are unresponsive to surgical stress and volume expansion.

Adult↗

Relation between bispectral index and plasma catecholamines after oral diazepam premedication.

The efficacy of anaesthetic premedication has been assessed using sedative scores or a visual analogue scale. However, in both it may be difficult to exclude evaluators' subjectivity or a placebo effect. Plasma concentration of catecholamines may also be useful for the assessment of patient anxiety. Recently bispectral electro-encephalographic analysis has been developed, and the bispectral index monitor has been reported to give measurements which correlate well with the depth of sedation. In the present study, we have examined the relation between bispectral index values and plasma catecholamine concentrations after oral diazepam premedication. Twenty-eight patients scheduled for elective surgery were randomly assigned to one of two groups: diazepam premedication group (group D(+), n = 14) and no premedication group (group D(-), n = 14). The patients were premedicated orally with diazepam 10 mg and roxatidine 75 mg in group D(+), and with roxatidine 75 mg only in group D(-) 90 min before arrival in the operating theatre. After patients arrived in the operating theatre, the bispectral index monitor was applied. Venous blood samples (6 mL) were collected in the case of patients in group D(+) for the measurement of plasma catecholamines levels using high-performance liquid chromatography. The bispectral index level (mean +/- SD) in group D(+): 93.5 +/- 773.5 was significantly lower than that in group D(-): 96.1 +/- 1.8 (P < 0.05). There was a significant correlation between bispectral index and plasma norepinephrine levels (r = 0.567, P < 0.05). The present study suggests that the bispectral index monitor may detect the effect of oral diazepam premedication.

Administration, Oral↗

The effects of nitrous oxide and ketamine on the bispectral index and 95% spectral edge frequency during propofol-fentanyl anaesthesia.

In this study, we have sought to establish whether N2O and ketamine alter the bispectral index during propofol-fentanyl anaesthesia. Fourteen surgical patients were randomly assigned to one of two groups: the N2O group (n = 7) and the ketamine group (n = 7). In both groups, anaesthesia was induced with propofol 1.5-2 mg kg-1 and fentanyl 2 micrograms kg-1 and maintained with propofol 5-7 mg kg-1 hr-1 to target the bispectral index between 40 and 50. After the bispectral index value had stabilized the propofol infusion rate was fixed. In the N2O group, the following concentrations of N2O were subsequently inhaled at 20-min intervals; 20, 40, 60 and 70%, and then N2O was terminated. In the ketamine group, ketamine (0.4 mg kg-1 + 1.0 mg kg-1h-1) was given. The bispectral index and 95% spectral edge frequency were recorded 20 min after each change in concentration of N2O or ketamine infusion. The bispectral index and 95% spectral edge frequency did not change significantly in the N2O group, but increased significantly from 44.1 +/- 0.7 and 16.0 +/- 0.5 to 58.6 +/- 1.4 and 19.5 +/- 0.3 (P < 0.01), respectively, in the ketamine group. Additional N2O or ketamine did not decrease the bispectral index and 95% spectral edge frequency values. The depth of sedation should be assessed carefully using a bispectral index monitor when these anaesthetic agents are used together.

Adult↗

Enzyme level of enterococcal F1Fo-ATPase is regulated by pH at the step of assembly.

The amount of F1Fo-ATPase in Enterococcus hirae (formerly Streptococcus faecalis) increases when the cytoplasmic pH is lowered below 7.6, and protons are extruded to maintain the cytoplasmic pH at around 7.6. In the present study, we found that the transcriptional activity of the F1Fo-ATPase operon was not regulated by pH. The synthesis of F1 subunits was increased 1.65 +/- 0.12-fold by the acidification of medium from pH 8.0 to pH 5.3. Western-blot analysis showed that there were F1 subunits in the cytoplasm, and the number of alpha plus beta subunits in the cytoplasm was 50% of the total number of the subunits in cells growing at pH 8.0. This decreased to 22% after shifting the medium pH to 5.3, with a concomitant 5.1-fold increase in the level of membrane-bound F1Fo-ATPase. The cytoplasmic F1 subunits were shown to be degraded, and Fo subunits not assembled into the intact F1Fo complex were suggested to be digested. These data suggest that regulation of the enzyme level of F1Fo-ATPase by the intracellular pH takes place mainly at the step of enzyme assembly from its subunits.

Cytoplasm↗

Differential effects of palmitate on glucose uptake in rat-1 fibroblasts and 3T3-L1 adipocytes.

Non-esterified fatty acids are thought to be one of the causes for insulin resistance. However, the molecular mechanism of fatty acid-induced insulin resistance is not clearly known. In this study, we first examined the effect of palmitate on insulin signaling in 3T3-L1 adipocytes. We found that 1h treatment with 1 mmol/l palmitate had no effect on insulin binding, tyrosine phosphorylation of insulin receptors, 185 kDa proteins and Shc, and PI3 kinase activity in 3T3-L1 adipocytes. Then, the effects of palmitate on MAP kinase activity and glucose uptake in fully differentiated 3T3-L1 adipocytes were compared with those in poorly differentiated 3T3-L1 cells and in HIRc-B cells. Palmitate treatment had no effect on MAP kinase activity in fully differentiated 3T3-L1 adipocytes, while it inhibited MAP kinase in poorly differentiated 3T3-L1 cells and HIRc-B cells. Glucose transport in 3T3-L1 adipocytes treated with palmitate for 1 h, 4 h and 16 h was higher than that in control cells, but palmitate treatment caused a rightward shift of the insulin-dose responsive curve for glucose uptake in HIRc-B cells. Palmitate treatment did not significantly affect basal and insulin-stimulated GLUT4 translocation. When the cells were treated with PD98059, a specific MEK inhibitor, insulin-stimulated glucose uptake was not affected in 3T3-L1 adipocytes, while it was almost completely inhibited in HIRc-B cells. These results suggest the primary effect of palmitate on adipocytes may not involve insulin resistance of adipocytes themselves.

3T3 Cells↗

I.v. lidocaine worsens histamine-induced bronchoconstriction in dogs.

We have assessed the effect of lidocaine (lignocaine) on histamine-induced bronchoconstriction by direct visualization with a superfine fibreoptic bronchoscope. Seven mongrel dogs were anaesthetized with pentobarbital (pentobarbitone) 30 mg kg-1 followed by 2 mg kg-1 h-1 and pancuronium 200 micrograms kg-1 h-1. The trachea was intubated with a tracheal tube containing a second lumen for insertion of a 2.2-mm fibreoptic bronchoscope. This allowed estimation of the bronchial cross-sectional area (BCA) of the third bronchial bifurcation of the right lung. We used NIH image, a public domain image processing and analysis program. Bronchoconstriction was produced with a bolus dose of histamine 10 micrograms kg-1 i.v. followed by continuous infusion of 500 micrograms kg-1 h-1. After 30 min the following i.v. doses of lidocaine were given: lidocaine 0 (saline), 0.01, 0.1, 1.0 and 10 mg kg-1 at 10-min intervals. BCA was assessed 90 s after each dose. Arterial blood sampling was performed for measurement of plasma catecholamines. Lidocaine 1.0 and 10 mg kg-1 significantly reduced histamine-decreased BCA from 69.7 (SEM 4.1)% to 59.8 (7.3)% and 34.3 (6.8)%, respectively. Plasma concentrations of catecholamines decreased significantly after lidocaine 10 mg kg-1 i.v. In addition, there was a significant correlation between percentage decreases in plasma concentrations of epinephrine (adrenaline) and norepinephrine (noradrenaline) and reduction in %BCA (epinephrine-BCA, P < 0.01, r = 0.674; norepinephrine-BCA, P < 0.01, r = 0.510). This study suggests that i.v. lidocaine may exacerbate histamine-induced bronchoconstriction by a sympatholytic effect. This may have therapeutic implications for patients with acute asthma or anaphylactic shock who may become dependent on circulating catecholamines.

Anesthetics, Intravenous↗