Increase In Plasma Epinephrine Concentration Research Articles

Biological Response to Stress During Battlefield Trauma Training: Live Tissue Versus High-Fidelity Patient Simulator.

Tactical Combat Casualty Care (TCCC) training imposes psychophysiological stress on medics. It is unclear whether these stress levels vary with the training modalities selected. It is also unclear how stress levels could have an impact on medical performance and skill uptake. We conducted a pilot study to compare the effects of live tissue (LT) with a high-fidelity patient simulator (SIM) on the level of stress elicited, performance, and skill uptake during battlefield trauma training course in an operating room (OR) and in a simulated battlefield scenario (field). In the report, we studied the effects of training modalities and their changes on stress levels by measuring different biomarkers (salivary amylase, plasma catecholamines, and neuropeptide Y) at various time points during the trauma training course. We found that the training resulted in significant psychophysiological stress as indicated by elevated levels of various biomarkers relative to baseline immediately after both OR and field assessment (p < 0.05). Compared with pre-OR levels, the LT training in the OR resulted in significant increases in the plasma levels of epinephrine, norepinephrine, and neuropeptide (p = 0.013, 0.023, 0.004, respectively), whereas the SIM training in the OR resulted in significant increases in the plasma levels of norepinephrine and neuropeptide (p = 0.003 and 0.008). Compared with pre-field levels, we found significant increases in plasma epinephrine concentration in the SIM group (p = 0.016), plasma norepinephrine concentration in the LT group (p = 0.015), and plasma neuropeptide Y concentration in both LT (p = 0.006) and SIM groups (p = 0.029). No differences in the changes of biomarker levels were found between LT and SIM groups in the OR and field. Compared with pre-field levels, the testing on the same modality as that in the OR in the simulated battlefield resulted in significant increases in norepinephrine and neuropeptide levels (p = 0.013 and 0.015), whereas the testing on different modalities resulted in significant increases in amylase, epinephrine, and neuropeptide levels (p = 0.016, 0.05, 0.018, respectively). There was a significantly larger increase in plasma norepinephrine concentration (p = 0.031) and a trend toward a greater increase in the salivary amylase level (p = 0.052) when the field testing involved a different modality than the OR compared with when OR and field testing involved the same modality. Although most of the biomarkers returned to baseline levels after 24 h, plasma norepinephrine levels remained significantly higher regardless of whether field testing occurred on the same or different modality compared with OR (p = 0.040 and 0.002). TCCC training led to significant increase in psychophysiological stress, as indicated by elevated levels of various biomarkers. The training modalities did not result in any differences in stress levels, whereas the switch in training modalities appeared to elicit greater stress as evidenced by changes in specific biomarkers (amylase and norepinephrine). A comparative study with a larger sample size is warranted.

Adrenergic response to maximum exercise of trained road cyclists.

The aim of this study was to evaluate adrenergic responses in the peripheral blood of trained road cyclists at rest, at maximal intensity of incremental bicycle exercise test, and during 15 minutes of recovery, as well as the relationship between them. Competitive male road cyclists, in the pre-competitive phase of a season, mean age 21.7 ± 6.4 years, and BMI 20.7 ± 0.8 kg·m−2, performed an incremental test on a bicycle ergometer with unloaded cycling for 5 min, then increased the load to 40 W every 3 min, up to maximal exercise intensity. The plasma catecholamine concentrations (epinephrine, norepinephrine) and oxygen uptake were estimated. The expression of 132 genes related to the adrenergic system in leukocytes was measured. A statistically significant increase in plasma epinephrine concentration (p < 0.01) was observed in response to exercise. The mean of maximal oxygen uptake was 65.7 ± 5.5 ml·kg−1·min−1. The RGS2 gene expression was highest regardless of the test phase for all athletes. The effort had a statistically significant influence on ADRB2 and RAB2A expression. In addition, the RAB2A, ADM and HSPB1 expression level increased during recovery. We can conclude that plasma epinephrine concentration and genes related to the adrenergic system such as ADM, ADRB2, CCL3, GPRASP1, HSPB1, RAB2A, RGS2 and ROCK1 seem to have an influence on the response to high-intensity exercise in trained cyclists.

Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans

The relative contributions of net hepatic glycogenolysis (NHG) and gluconeogenesis to rates of glucose production during a physiological increment in plasma epinephrine concentrations, independent of changes in plasma insulin concentrations, were determined in seven fasting, healthy young subjects. Plasma insulin concentrations were kept constant by infusing somatostatin (0.1 microg.kg(-1).min(-1)) and replacing basal insulin (24 pmol.m(-2).min(-1)). Epinephrine (1.2 microg.m(-2).min(-1)) was infused for 90 min while NHG was assessed directly by (13)C magnetic resonance spectroscopy. The rate of glucose production was assessed using [6,6-(2)H(2)]glucose, and gluconeogenesis was calculated as the difference between the rate of glucose production and NHG. Plasma epinephrine concentrations increased rapidly from approximately 100 to approximately 2,000 pmol/l (P < 0.00001) accompanied by an increase in plasma glucose concentrations from 4.3 +/- 0.2 to 13.3 +/- 0.3 mmol/l at 90 min (P = 0.00001). This increase in plasma epinephrine concentration resulted in a 2.5-fold increase in glucose production (from 14.4 +/- 1.0 micromol.kg(-1).min(-1) to 35.7 +/- 2.0 micromol.kg(-1).min(-1), P < 0.0001), which lasted for approximately 60 min (phase 1), after which glucose production decreased to 31.2 +/- 1.9 micromol.kg(-1).min(-1) (P < 0.0001 vs. basal) during the last 30 min of the epinephrine infusion (phase 2). Hepatic glycogen concentrations decreased almost linearly during phase 1, and rates of NHG were 19.9 +/- 3.0 micromol.kg(-1).min(-1) (P = 0.005 vs. basal), which could account for approximately 60% of glucose production. During phase 2, NHG decreased to 7.3 +/- 2.8 micromol.kg(-1).min(-1) (P = 0.02 vs. peak), accounting for only approximately 20% of glucose production. In conclusion, in the presence of basal plasma insulin and glucagon concentrations, a physiological increase in plasma epinephrine concentrations stimulates glucose production with an initial, 60-min transient phase caused by stimulation of NHG and a second phase that can mostly be attributed to a twofold increase in rates of gluconeogenesis.

ROLE OF BRAIN PROSTANOIDS IN GLUCAGON‐LIKE PEPTIDE‐1‐INDUCED CENTRAL ACTIVATION OF SYMPATHO‐ADRENOMEDULLARY OUTFLOW IN RATS

1. The aim of the present study was to characterize the source of plasma catecholamines induced by centrally administered glucagon-like peptide-1 (GLP-1), with regard to brain prostanoids, in urethane-anaesthetized rats. 2. Glucagon-like peptide-1 and other compounds were administered intracerebroventricularly (i.c.v.) and blood samples were collected via a cannula inserted into the femoral artery. Catecholamines were extracted from plasma with activated alumina and were assayed electrochemically using high-performance liquid chromatography. 3. At 0.3, 1.0 and 3.0 nmol/animal, GLP-1 dose-dependently elevated plasma levels of noradrenaline and adrenaline and the 1.0 nmol GLP-1-induced response was dose-dependently reduced by 5 and 10 nmol/animal exendin (5-39), a selective GLP-1 receptor antagonist. The GLP-1-induced elevation of concentrations of both catecholamines was abolished by 1.2 micromol/animal indomethacin, an inhibitor of cyclo-oxygenase, whereas 1.2 micromol/animal baicalein, a lipoxygenase inhibitor, had no effect. 4. Both furegrelate (1.8 micromol/animal; an inhibitor of thromboxane A(2) synthase) and (+)S-145 (625 nmol/animal; a thromboxane A(2) receptor antagonist) attenuated the GLP-1-induced increases in plasma adrenaline concentrations, but had no effect on the increases in plasma noradrenaline. The GLP-1-induced increase in plasma adrenaline concentrations was abolished by acute bilateral adrenalectomy, but the procedure had no effect on increases in plasma noradrenaline. 5. These results suggest that, in rats, centrally administered GLP-1 induces the secretion of adrenaline from the adrenal medulla by brain thromboxane A(2)-mediated mechanisms, whereas the peptide evokes the release of noradrenaline from sympathetic nerves by brain prostanoids via mechanisms other than those mediated by thromboxane A(2).

Modulation of hypoglycemia‐induced increases in plasma epinephrine by estrogen in the female rat

Clinical studies have demonstrated that estrogen replacement therapy suppresses stress-induced increases in plasma catecholamines. The present study determined whether normal circulating levels of estrogen can modulate hypoglycemia-induced increases in plasma epinephrine (EPI). In anesthetized female rats, insulin-induced hypoglycemia (0.25 U/kg) increased plasma EPI concentration to a significantly greater extent in 14-day ovariectomized (OVEX) rats compared to that in sham-operated controls. In 17beta-estradiol (E2)-replaced OVEX rats, the hypoglycemia-induced rise in plasma EPI was reduced significantly when compared to that in vehicle-replaced OVEX rats. OVEX and E2 replacement had no effect on tyrosine hydroxylase or phenylethanolamine N-methyltransferase mRNA levels in the adrenal medulla. In isolated adrenal medullary chromaffin cells, agonist-induced increases in intracellular Ca2+ were unaffected by 48-hr exposure to 10 nM E2. In contrast, acute (3-min) exposure to micromolar concentrations of E2 dose-dependently and reversibly inhibited agonist-induced Ca2+ transients. In addition, in OVEX rats, a constant infusion of E2 significantly reduced the insulin-induced increase in plasma EPI concentration compared to that in vehicle-infused controls. These data demonstrate that physiologic levels of circulating E2 can modulate hypoglycemia-induced increases in plasma EPI. This effect seems independent of steroid influence on adrenal medullary secretion or biosynthesis. In contrast, acute exposure to high levels of E2 can also suppress hypoglycemia-induced increases in plasma epinephrine, due at least in part to inhibition of stimulus-secretion coupling.

Effects of Fragrance Inhalation on Sympathetic Activity in Normal Adults

We investigated the effects of fragrance inhalation on sympathetic activity in normal adult subjects using both power spectral analysis of blood pressure fluctuations and measurement of plasma catecholamine levels. Fragrance inhalation of essential oils, such as pepper oil, estragon oil, fennel oil or grapefruit oil, resulted in 1.5- to 2.5-fold increase in relative sympathetic activity, representing low frequency amplitude of systolic blood pressure (SBP-LF amplitude), compared with inhalation of an odorless solvent, triethyl citrate (P<0.05, each). In contrast, fragrance inhalation of rose oil or patchouli oil caused a 40% decrease in relative sympathetic activity (P<0.01, each). Fragrance inhalation of pepper oil induced a 1.7-fold increase in plasma adrenaline concentration compared with the resting state (P = 0.06), while fragrance inhalation of rose oil caused a 30% decrease in adrenaline concentration (P<0.01). Our results indicate that fragrance inhalation of essential oils may modulate sympathetic activity in normal adults.

Oral mucosal blood flow, plasma epinephrine and haemodynamic responses after injection of lidocaine with epinephrine during midazolam sedation and isoflurane anaesthesia

We have investigated the relationship between oral mucosal blood flow and plasma epinephrine concentration, and the effects of conscious sedation vs general anaesthesia on haemodynamic responses after submucosal epinephrine injection in 14 subjects. The same seven patients were studied both as controls and after sedation. For sedation, midazolam i.v. was used. Another seven patients underwent orthognathic surgery with isoflurane anaesthesia. All subjects received a submucosal injection of epinephrine 0.8 microgram kg-1, given as 2% lidocaine hydrochloride with epinephrine 12.5 micrograms ml-1. Baseline mucosal blood flow and peak increase in plasma epinephrine concentration in the general anaesthesia and sedation groups were approximately 2.0 and 1.5 times, respectively, higher than those in the control group. Mean plasma epinephrine concentration reached a maximum 3 min after administration of epinephrine in all groups. Overall, there was a significant correlation (r = 0.65) between baseline mucosal blood flow and the maximum increase in plasma epinephrine concentration. There were no differences in haemodynamic changes except for heart rate, between the three groups. These results suggest that plasma epinephrine concentration after submucosal injection depends on the initial mucosal blood flow in the injected area. Haemodynamic changes, except heart rate, in the sedation and general anaesthesia groups were similar despite different changes in maximum plasma epinephrine concentration.

ELEVATION OF END-TIDAL CARBON DIOXIDE TENSION AFTER ORAL MUCOSAL EPINEPHRINE INJECTION MAY BE A USEFUL NONINVASIVE MONITOR FOR CARDIAC OUTPUT IN HUMANS

S213 INTRODUCTION: End-tidal carbon dioxide tension(PETCO2: may change by several mechanisms including increase in cardiac output(CO), metabolic rate, and/or physiological deadspace (VD/VT) after epinephrine injection [1]. Further it has been reported that PETCO2 changes are directly correlated with CO changes [2]. In the present study, we sought to determine whether a relationship exists between PETCO2 elevation and CO increase after oral mucosal epinephrine injection. METHODS: Following institutional approval and informed consent, 15 ASA I patients (19-35 yrs) scheduled for orthognathic surgery were studied. Anesthesia was induced with IV propofol (2.5 mg/kg) and fentanyl (2 [micro sign]g/kg), and nasotracheal intubation was facilitated with vecuronium bromide (0.2 mg/kg). Anesthesia was maintained with continuous infusion of propofol (12 mg/kg/hr) and mechanically ventilated (FiO2: 0.3). Before the beginning of surgery, 1% lidocaine solution containing 10 [micro sign]g/ml epinephrine (total dose: 0.5-2.0 [micro sign]g/kg) was injected into the oral mucosa in over two minutes. The following variables were measured plasma epinephrine concentration (high performance liquid chromatography), PETCO2(Capnomac[registered sign]; Datex), PaCO2, PaO2, CO (NCCOM3-R7[registered sign]; CDIC), carbon dioxide output(VCO2), oxygen consumption(VO2) (DELTATRAC[registered sign]; Datex), arterial blood pressure, and heart rate. The operation was started 15 minutes after the completion of epinephrine injection. RESULTS: The maximum increase in plasma epinephrine concentrations were significantly correlated with PETCO2 elevation (r=0.68, p<0.01) and CO increase (r=0.62, p<0.01). Figure 1 shows the time course of the measured variables. Both PETCO2 and CO showed a precipitous increase up to 6 minutes after epinephrine injection. Further, there was a significant correlation between PETCO2 elevation and CO increase (r=0.62, p<0.01, Figure 2).Figure 1Figure 2DISCUSSION: The changes in CO, metabolic rate, and VD/VT may modify PETCO2 and PaCO2. Our results seem to indicate that the increase in metabolic rate caused PETCO2 elevation. PETCO2 elevation and CO increase also did have a significant correlation which occurred concomitantly. The clinical significance is that PETCO2 elevation after oral mucosal epinephrine injection may be a useful noninvasive monitor for CO.

Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans

To examine the effects of a physiological increase in plasma epinephrine concentration (approximately 800 pg/ml) on muscle glycogenolysis and insulin-stimulated glycogenesis, we infused epinephrine [1.2 micrograms.(m2 body surface)-1.min-1] for 2 h and monitored muscle glycogen and glucose 6-phosphate (G-6-P) concentrations with 13C/31P nuclear magnetic resonance (NMR) spectroscopy. Epinephrine caused an increase in plasma glucose (delta approximately 50 mg/dl), lactate (delta approximately 1.4 mM), free fatty acids (delta approximately 1,200 microM at peak), and whole body glucose oxidation (delta approximately 0.85 mg.kg-1.min-1) compared with levels in a group of control subjects (n = 4) in the presence of slight hyperinsulinemia (approximately 13 microU/ml, n = 8) or basal insulin (approximately 7 microU/ml, n = 7). However, epinephrine did not induce any detectable changes in glycogen or G-6-P concentrations, whereas muscle inorganic phosphate (Pi) decreased by 35%. Epinephrine infusion during a euglycemic-hyperinsulinemic clamp (n = 8) caused a 45% decrease in the glucose infusion rate that could be mostly attributed to a 73% decrease in muscle glycogen synthesis rate. After an initial increase to approximately 160% of basal values, G-6-P levels decreased by approximately 30% with initiation of the epinephrine infusion. We conclude that a physiological increase in plasma epinephrine concentration 1) has a negligible effect on muscle glycogenolysis at rest, 2) decreases muscle Pi, which may maintain phosphorylase activity at a low level, and 3) causes a major impairment in insulin-stimulated muscle glycogen synthesis, possibly due to inhibition of glucose transport-phosphorylation activity.

AT 1 and AT 2 Receptor Blockade and Epinephrine Release During Insulin-Induced Hypoglycemia

Angiotensin II facilitates epinephrine release during insulin-induced hypoglycemia, and this effect appears to be independent of type 1 angiotensin II (AT1) receptors in man. In the present study, we hypothesized that the action of angiotensin II on adrenomedullary epinephrine release is mediated by an AT2 receptor-dependent mechanism. In conscious chronically instrumented rats, we measured plasma concentrations of catecholamines during acute insulin-induced hypoglycemia in groups of rats pretreated with the AT1 receptor antagonist losartan (10 mg/kg i.v.), the AT2 receptor antagonist PD123319 (30 mg/kg i.v.), combined losartan + PD123319, the converting enzyme inhibitor enalapril (1 mg/kg i.v.), or vehicle. In vehicle-treated rats, the area under the curve for changes in plasma epinephrine concentration [AUC(plasma epinephrine)] during insulin-induced hypoglycemia was 111+/-8 nmolXh/L (+/-SEM). Pretreatment with losartan alone did not affect AUC(plasma epinephrine) (113+/-17 nmol x h/L), while pretreatment with PD123319 tended to reduce the response (87+/-10 nmol x h/L; P=.08 versus vehicle). However, AUC(plasma epinephrine) was significantly reduced in rats that were pretreated with combined losartan + PD123319 (68+/-5 nmol x h/L; P<.001 versus vehicle) or enalapril: 86+/-10 nmol x h/L (P<.05 versus vehicle). Thus, combined treatment with losartan + PD 123319 proved more effective in attenuating the reflex increase in plasma epinephrine concentration during hypoglycemia than either of the two AT receptor antagonists given alone. We speculate that angiotensin II through binding to both receptor subtypes facilitates the sympathoadrenal reflex response by actions at several anatomical levels of the neural pathways involved in the sympathoadrenal reflex response elicited during insulin-induced hypoglycemia.

Arteriovenous differences in plasma concentration of nicotine and catecholamines and related cardiovascular effects after smoking, nicotine nasal spray, and intravenous nicotine.

Delivery of a high concentration bolus of nicotine through the arterial circulation is believed to be an important determinant of the addictive, behavioral, and physiologic effects of nicotine. To better understand the pharmacologic features of nicotine with different routes of administration, we measured arterial and venous plasma concentrations of nicotine, cotinine, epinephrine, and norepinephrine after tobacco smoking, intravenous nicotine infusion, and use of a nicotine nasal spray. Arterial and venous blood samples were drawn simultaneously from 12 male smokers. Six subjects received a single dose of 1 mg nicotine nasal spray, and six subjects smoked cigarettes, one puff per minute for 10 minutes. All 12 subjects were administered nicotine as a 30-minute infusion beginning 70 minutes after administration of the nicotine nasal spray or commencement of smoking. The mean peak arterial plasma concentrations of nicotine (Cmax) after smoking or administration of nicotine nasal spray, or intravenous nicotine averaged twofold those of venous plasma. For nicotine nasal spray, the time to Cmax was much faster for arterial than for venous plasma (median, 5 versus 18 minutes, p < 0.01). Intravenous nicotine produced the greatest increase in plasma epinephrine concentration, although smoking had a greater chronotropic effect. Acute tolerance to the chronotropic effects of nicotine was suggested at pharmacodynamic analysis with venous nicotine concentrations, whereas analysis of arterial concentrations found the opposite--a time lag between plasma concentration and effect. Nicotine is rapidly absorbed from nicotine nasal spray. The Cmax of nicotine after smoking or administration of nicotine nasal spray, or intravenous nicotine is substantially higher in arterial than venous plasma. Acute tolerance to the chronotropic effects of nicotine is not apparent if arterial plasma concentrations are measured.

Effects of various beverages on the hormones involved in energy metabolism during exercise in the heat in previously dehydrated subjects.

The objective of our study was to examine the effects of beverage content on hormone responses involved in fuel substrate metabolism (catecholamines, insulin and glucagon) in previously dehydrated subjects exercising at a moderate intensity in the heat. Six healthy men walked for 60-min on five occasions at 50% maximal oxygen uptake in a warm environment (dry bulb temperature 35 +/- 0.2 degrees C, relative humidity 20%). On each occasion, the subjects were dehydrated before exercise (loss of 2% body mass) by passive controlled hyperthermia, which led to a reduction in plasma volume (PV) of about -5% to -9%. In one session, the subjects exercised without rehydration (Dh). In the other sessions, four beverages (650 ml) were given just before the exercise: mineral water (W), a 60 g x l(-1) glucose and 1.2 g x l(-1) NaCl solution (GS), a 60 g x l(-1) maltodextrin solution, and a 60 g x l(-1) maltodextrin and 1.2 g x l(-1) NaCl solution. Compared to Dh and W, carbohydrate supply with or without NaCl induced a higher glycaemia (P < 0.05), a reduced increase in plasma adrenaline concentration (P < 0.05) and a higher plasma insulin concentration (P < 0.05), which lowered plasma free fatty acids and glycerol concentrations (P < 0.05). The lesser increase in plasma noradrenaline concentrations observed during GS compared to Dh and W sessions can be explained by a larger correction in PV which might have induced better haemodynamic conditions. However, the increase in plasma glucagon with carbohydrate supply--compared to Dh and W (P < 0.05)--remains unexplained.

Captopril does not Blunt the Sympathoadrenal Response to Cigarette Smoking in Normotensive Humans

Ottesen M. M., Worck R and Ibsen H. Captopril does not blunt the sympathoadrenal response to cigarette smoking in normotensive humans.The aim of this study was to assess whether an interaction exists between the renin-angiotensin system and the sympathetic nervous system at the level of the adrenal medulla during smoking in normal humans. Thirteen habitual smoking volunteers were studied in a randomized, single-dose, double-blind, cross-over fashion using 50 mg captopril vs placebo followed by smoking of two high nicotine content cigarettes within 15 min. Blood samples were obtained at frequent intervals before, during and after smoking. We found that the increase in plasma adrenaline concentration during cigarette smoking was modest. There was no difference between captopril treatment as compared to placebo. Thus, the adrenaline response to cigarette smoking was not blunted by acute blockade of angiotensin IT generation. A significant increase in heart rate, and blood pressure was found as well. No increase in plasma noradrenaline concentration was found. Plasma renin concentration increased significantly during captopril treatment, whereas it decreased throughout the study period in the placebo phase. Plasma angiotensin II concentration decreased in both the captopril treatment and the placebo phase throughout the study period, but this was more pronounced during captopril treatment. In conclusion, cigarette smoking-induced activation of the sympathetic nervous system was not blunted by acute ACE-inhibition by captopril. This indicates that angiotensin II does not facilitate smoking-induced activation of sympathoadrenal activity in humans.

Role of epinephrine-induced hypokalemia in the regulation of renin and aldosterone in humans

Circulating epinephrine induces both stimulation of plasma renin activity (PRA) and a decrease in serum potassium concentration. This study was designed to determine the dose-response effects of systemic epinephrine infusion on the relationship of PRA and plasma aldosterone concentration. Twenty-one men with normal blood pressure received either an intravenous infusion of epinephrine at 12.5, 25, and 50 ng/(kg × min) by stepwise increments for 1 hour each or isotonic saline solution. Infusion of epinephrine led to a dose-dependent increase in plasma epinephrine concentration, systolic blood pressure, and heart rate, whereas diastolic blood pressure was decreased. PRA was elevated in a dose-dependent manner, whereas the plasma aldosterone concentration was reduced. During infusion of epinephrine, the serum potassium concentration and renal potassium excretion were significantly decreased. We conclude that despite marked stimulation of PRA, the plasma aldosterone concentration was further decreased because of a dose-dependent decrease in serum potassium concentration induced by epinephrine. Thus hypokalemia appears to be the predominant regulator of plasma aldosterone during incremental epinephrine infusion.

Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery

Study Objective: To assess the efficacy and safety of intravenous (IV) dexmedetomidine, an alpha-2 agonist, as a premedication before N regional anesthesia. Design: Randomized, double-blind, placebo-controlled study with two parallel groups. Setting: Day-case surgery unit, Department of Surgery, Turku University Hospital, Turku, Finland. Patients: 30 healthy ASA physical status I outpatients scheduled for minor hand surgery with IV regional anesthesia. Interventions: Patients were assigned to one of two groups to receive either dexmedetomidine 1 μg/kg IV (n = 15) or saline placebo IV (n = 15) 10 minutes before exsanguination and inflation of a tourniquet. Regional blockade was induced with 0.5% lidocaine 3 mg/kg (maximum 200 mg). Additional fentanyl 1 μg/kg introoperatively and oxycodone 0.05 mg/kg postoperatively were administered for analgesia if needed. Measurements and Main Results: Dexmedetomidine preoperatively induced 16% to 20% decreases in systolic blood pressure (p < 0.001), diastolic blood pressure ( p < 0.001), and heart rate ( p < 0.001), which were mainly abolished within the 4-hour postoperative follow-up period. A clinically significant decrease in arterial oxygen saturation was not observed. The subjective intensity of pain during tourniquet inflation was similar in both groups, but fewer intraoperative ( p = 0.009) opioid analgesics were needed in the dexmedetomidine group. Dexmedetomidine decreased sympathoadrenal responses: plasma norepinephrine concentration decreased to one fourth of the baseline level ( p < 0.001), and one of its main metabolites, 3,4dihydroxyphenylglycol, decreased by 27% ( p < 0.001). Dexmedetomidine also prevented an increase in plasma epinephrine concentration following tourniquet inflation ( p = 0.003). Dexmedetomidine induced subjective sedation ( p = 0.002), but the Maddox Wing test did not show any statistically significant differences between the groups. General effectiveness was graded superior in the dexmedetomidine group ( p < 0.001). Conclusions: Dexmedetomidine is an effective premedication before Nregional anesthesia because it reduces patient anxiety, sympathoadrenal responses, and opioid analgesic requirements.

Sympathoadrenal-circulatory regulation of arterial pressure during orthostatic stress in young and older men.

Our purpose was to test the hypothesis that human aging alters sympathoadrenal-circulatory control of arterial blood pressure during orthostasis. Plasma catecholamine and hemodynamic adjustments to two different forms of orthostatic stress, lower body suction (-10 to -50 mmHg) and standing, were determined in 14 young (26 +/- 1 yr) and 13 older (64 +/- 1) healthy, normally active men. During quiet supine rest, cardiac output tended to be lower and systemic vascular resistance higher in the older men, but no other differences were observed. On average, arterial blood pressure was well maintained during both forms of orthostasis in the two groups; the older men actually demonstrated better maintenance of pressure (P < 0.05) and a lesser incidence of orthostatic hypotension than the young men during lower body suction. Despite a blunted reflex tachycardia during orthostatic stress (P < 0.05), cardiac output tended to decrease less in the older men because of a smaller decline in stroke volume (P < 0.05, suction only), whereas the reflex increases in systemic vascular resistance were not different in the two groups. The whole forearm vasoconstrictor response tended to be attenuated in the older men during lower body suction, but was identical in the two groups with standing. Forearm skin vascular resistance was unaltered during lower body suction in both groups. Orthostasis-evoked increases in antecubital venous plasma norepinephrine concentrations were similar in the young and older men, whereas little or no increases in plasma epinephrine concentrations were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses of glucose and glucoregulatory hormones to exercise in thyrotoxic and myxoedematous patients before and after 3 months of treatment.

1. The effect of moderate endurance exercise on blood glucose concentration and on glucoregulatory hormones was studied in nine thyrotoxic and five myxoedematous humans before and 3 months after anti-thyroid and substitution therapy, respectively. 2. At rest, the fasting concentrations of insulin and pro-insulin correlated positively with the prevailing total tri-iodothyronine concentration, whereas the concentrations of noradrenaline and cortisol correlated inversely with the tri-iodothyronine concentration. 3. During exercise the plasma insulin, pro-insulin and C-peptide concentrations decreased. The plasma glucagon concentration increased slightly in thyrotoxic patients before and after treatment and was largely unchanged in myxoedematous patients in either state. 4. The plasma noradrenaline concentration increased before and after treatment in both groups, with concentrations two times higher in the myxoedematous than in the thyrotoxic patients. Treatment for 3 months did not change this pattern. The plasma adrenaline concentration increased in both groups, but in the untreated thyrotoxic patients the increase was two to three times greater than that after treatment or that in the myxoedematous group. 5. The blood glucose concentration decreased in eight of nine untreated thyrotoxic patients, but was largely unchanged after treatment or in the myxoedematous patients. A strong negative correlation was found between the decline in blood glucose concentration and the increase in plasma adrenaline concentration in the thyrotoxic group. 6. Thus, during exercise untreated thyrotoxic patients are prone to hypoglycaemia, show an inadequate glucagon response, and exhibit a large counter-regulatory increase in plasma adrenaline concentration.

Deficient Counterregulatory Hormone Responses during Hypoglycemia in a Patient with Insulinoma*

Counterregulatory hormone responses were evaluated in a 37-yr-old woman before and after removal of a benign insulin-producing islet cell tumor. Counterregulatory hormone concentrations were measured during a glucose clamp with graded reductions of plasma glucose from 5.2 to 2.6 mmol/L. In the study before surgery, the increase in plasma epinephrine concentration was markedly blunted (by greater than 90%) compared to that in the study after surgery. The peak plasma norepinephrine concentration was similarly reduced by 71%, and plasma cortisol by 63%. In addition, the glycemic thresholds for secretion of the counterregulatory hormones were lower before removal of the tumor. Peak plasma GH responses were equivalent before and after surgery, but the threshold for GH secretion was 21% lower in the first hypoglycemia study. We conclude 1) that there is evidence for abnormal glucose counterregulatory hormone secretion in this patient, which may contribute to the pathogenesis of hypoglycemia seen in patients with insulinoma; 2) the reversal of reduced counterregulatory hormone secretion after tumor resection suggests that these defective hormonal responses may be related to recurrent hypoglycemia, persistent hyperinsulinemia, or both; and 3) that abnormal glucose counterregulation may exist in the absence of type 1 diabetes.

Plasma concentrations of epinephrine during CPR in the dog

The purpose of this study was to evaluate whether the marked increase in the plasma concentrations of epinephrine during cardiopulmonary arrest and basic life support (BLS) could be due in part to decreased distribution and/or elimination. Dogs were randomly assigned to undergo adrenalectomy or sham-operation. Some adrenalectomized animals received an epinephrine infusion. In the seven sham-operated dogs, the plasma epinephrine concentrations increased markedly during BLS as expected. In the seven adrenalectomized dogs receiving a constant infusion of epinephrine, cardiopulmonary arrest and BLS induced a three to sixfold increase in plasma epinephrine concentrations, with an increase in the mean plasma epinephrine concentrations (calculated from the area under the curve) of 1.21 +/- 0.12 ng/mL (P less than .05). In the seven adrenalectomized dogs receiving a constant epinephrine infusion but not subjected to cardiopulmonary arrest, the plasma epinephrine concentrations remained stable. Finally, in the seven adrenalectomized dogs not receiving an epinephrine infusion, the mean plasma epinephrine concentrations during BLS (calculated from the area under the curve) increased only by 0.05 +/- 0.04 ng/mL, significantly less than in adrenalectomized dogs receiving an epinephrine infusion (P less than .01). The increase in plasma epinephrine concentrations during cardiopulmonary arrest and BLS is due in part to an altered disposition of epinephrine.

Evaluation of shock-related cardiotoxic peptide.

The aim of the present work is to confirm the presence of MDF (myocardial depressant factor), which has long been postulated to be one of the cardiotoxic substances in the shock state. Twenty male mongrel dogs were divided into two groups, a hemorrhagic shock group (n = 10) and an endotoxic shock group (n = 10). Blood samples were obtained from each animal at 1, 2, 4, and 7 h after hypotensive events occurred. Inotropic properties of the plasma samples were evaluated by the isometric contraction of a cat papillary muscle preparation, and chromatographic analysis was performed on the peptides in the plasma. Developed tension of the muscle was increased significantly by changing the bathing medium from Krebs-Henseleit solution to plasma obtained 1 to 4 h after the onset of hemorrhagic and endotoxin induced hypotension. The positive inotropic change was associated with a significant increase in plasma epinephrine concentration. None of these plasma samples possessed a negative inotropic effect (i.e., the property of MDF activity). The elution profile by gel column chromatography of samples obtained from shocked animals was almost identical to that recognized as MDF. However, the presence of MDF was not confirmed by column parameters and color development by the ninhidrin reaction. In conclusion, we found no evidence to support the presence of cardiotoxic peptide in plasma of shocked animals.