Higher Epinephrine Levels Research Articles

Elevated Troponin Levels Are Associated with Sympathoadrenal Activation in Acute Ischaemic Stroke

Background: It has been hypothesised that elevated serum troponin levels in acute stroke are due to myocardial damage caused by sympathoadrenal activation, which, in turn, may be due particularly to insular damage. We aimed to determine the factors associated with troponin elevation in ischaemic stroke and the prognostic value of this finding. Methods: We studied 222 consecutive acute ischaemic stroke admissions. Serum troponin I and catecholamines were measured. Ischaemic damage on brain computed tomography (CT) scan was graded using the Alberta Stroke Program Early CT Score (ASPECTS). Electrocardiograms were classified using the Minnesota Code and the European Society of Cardiology/American College of Cardiology criteria for acute myocardial infarction. The Rankin scale was recorded at 30 days. Results: Forty-five patients (20%) had troponin I >0.2 µg/l. These troponin-positive patients had higher epinephrine levels (median 0.27 vs. 0.17 nmol/l; p = 0.0002) and were more likely to have electrocardiograms coded as definite or possible acute myocardial infarction (odds ratio 3.35; 95% CI 1.26–8.93), compared with those with troponin ≤0.2 µg/l, in univariate analysis. There were no significant associations between troponin I score and ASPECTS or insular damage on brain CT. In logistic regression analyses, elevated troponin was significantly associated with age, elevated serum creatinine and epinephrine; however, increased troponin was not an independent predictor of death or dependency (Rankin >2) at 30 days. Conclusions: Raised troponin I is associated with elevation of circulating epinephrine in acute ischaemic stroke. Activation of the sympathoadrenal system may be an important contributor to myocardial damage in these patients. Increased troponin is not associated with insular damage and does not independently predict poor outcome.

Insertion/Deletion Polymorphism on ACE Gene is Associated with Endothelial Dysfunction in Young Patients with Hypertension

Endothelial dysfunction, insulin resistance (IR) and genetic predispositions are important risk factors of hypertension. Aim of our study was to test the hypothesis, whether insertion/deletion (I/D) polymorphism on the angiotensin converting enzyme (ACE) gene and M235T polymorphism on angiotesinogen gene (AGT) correlates with parameters of insulin sensitivity and plasminogen activator inhibitor (PAI-1) levels in newly diagnosed hypertensive patients as compared with normotensive controls. Blood pressure (BP), fasting plasma glucose, insulin, epinephrine, norepinephrine and PAI-1 concentrations were determined in 30 male patients with hypertension grade 1 (HT) and in 31 matched healthy subjects (NT). Insulin resistance was estimated using IR HOMA formula. Patients with HT had increased levels of PAI-1, norepinephrine, fasting plasma insulin levels, IR HOMA (p<0.001) compared to controls. Subjects (HT and NT) with DD and ID genotype had a significantly higher systolic BP (p<0.05) and PAI-1 compared to those with II genotype. Homozygous subjects 235T had a higher systolic BP and higher levels of epinephrine and norepinephrine than heterozygous or homozygous M235 (p<0.05). In conclusion, no association was found between M235T polymorphism and insulin resistance or PAI-1 levels, but results indicate relationship between I/D polymorphism of the ACE gene and plasma PAI-1 levels in the early stage of hypertension.

Moods in everyday situations: effects of menstrual cycle, work, and stress hormones

Objective This study examined women's mood responsiveness on work and off days during different phases of the menstrual cycle. Methods Self-reports of negative, positive, and energy dimensions of mood were obtained throughout the day on two work and two off days during the luteal and follicular phases of the menstrual cycle in 203 women nurses. Individual differences in daytime and nighttime epinephrine, norepinephrine, and cortisol were assessed. Results High daytime norepinephrine, epinephrine, and cortisol levels were associated with higher ratings of stress and tired, and with lower ratings of happy. The phase of the menstrual cycle and the day factor (workday, off day) were also associated with mood differences, and the direction of the effects depended on hormone levels and hormone sampling period. Conclusion The experience of moods is affected by the arousal-related interaction of hormone levels with the phase of the menstrual cycle and occupational stress.

Initial urinary epinephrine and cortisol levels predict acute PTSD symptoms in child trauma victims

Previous research examining biological correlates of posttraumatic stress disorder (PTSD) in children has suggested that children with chronic PTSD have altered levels of catecholamines and cortisol compared to similarly traumatized children who do not meet diagnostic criteria. The present study extended these findings by examining whether urinary hormone levels collected soon after a trauma were related to subsequent acute PTSD symptoms in child trauma victims. Initial 12-h urine samples were collected from 82 children aged 8-18 admitted to a Level 1 trauma center. Collection was begun immediately upon admission, and samples were assayed for levels of catecholamines and cortisol. PTSD and depressive symptomatology were assessed 6 weeks following the accident. Initial urinary cortisol levels were significantly correlated with subsequent acute PTSD symptoms (r=0.31). After removing the variance associated with demographic variables and depressive symptoms, urinary cortisol and epinephrine levels continued to predict a significant percentage (7-10%) of the variance in 6-week PTSD symptoms. Examination of boys and girls separately suggested that significance was primarily driven by the strength of the relationships between hormone levels and acute PTSD symptoms in boys. The present findings suggest that high initial urinary cortisol and epinephrine levels immediately following a traumatic event may be associated with increased risk for the development of subsequent acute PTSD symptoms, especially in boys.

Epinephrine producing pheochromocytoma. Is the secretory pattern decisive for the clinical manifestation?

Adrenal incidentalomas are becoming a major clinical problem, due to increasingly frequent radiological examinations. We present two cases of patients referred to our department with a finding of an unsuspected adrenal mass. Both of them were normotensive and without symptomatology typical for pheochromocytoma. In one patient we found 20-times higher levels of epinephrine and 3-times higher levels of dopamine in 24-h urine, in the second patient there were 8-times higher levels of epinephrine alone. Norepinephrine in urine, as well as values of all adrenal cortical hormones were normal. The diagnosis of pheochromocytoma was confirmed in both cases by a 123I-metaiodobenzylguanidine (MIBG) scintigraphy. The patients underwent adrenalectomy, which was performed without complications. We conclude that levels of single catecholamines excreted are decisive for the clinical presentation of pheochromocytoma. Epinephrine producing pheochromocytoma is more often oligo- or asymptomatic. We stress the importance of a complete hormonal screening in every case of adrenal incidentaloma, with measuring levels of catecholamines and/or metanephrines.

Effects of plasma adrenaline on hormone-sensitive lipase at rest and during moderate exercise in human skeletal muscle.

We investigated the effect of increased plasma adrenaline on hormone-sensitive lipase (HSL) activity and extracellular regulated kinase (ERK) 1/2 phosphorylation during exercise. Seven untrained men rested for 20 min and exercised for 10 min at 60 % peak pulmonary oxygen uptake on three occasions: with adrenaline infusion throughout rest and exercise (ADR), with no adrenaline infusion (CON) and with adrenaline infusion commencing after 3 min of exercise (EX+ADR). Muscle samples were obtained at rest before (Pre, -20 min) and after (0 min) infusion, and at 3 and 10 min of cycling. Exogenous adrenaline infusion increased (P < 0.05) plasma adrenaline at rest during ADR, which resulted in greater HSL activity (Pre, 2.14 +/- 0.10 mmol min-1 (kg dry matter (dm))-1; 0 min, 2.74 +/- 0.20 mmol min-1 (kg dm)-1). Subsequent exercise had no effect on HSL activity. During exercise in CON, HSL activity was increased (P < 0.05) above rest at 3 min but was not increased further by 10 min. The infusion of exogenous adrenaline at 3 min of exercise in EX+ADR resulted in a marked elevation in plasma adrenaline levels (3 min, 0.57 +/- 0.12 nM; 10 min, 10.08 +/- 0.84 nM) and increased HSL activity by 25 %. HSL activity at 10 min was greater (P < 0.05) in EX+ADR compared with CON. There were no changes between trials in the plasma concentrations of insulin and free fatty acids (FFA) and the muscle contents of free AMP, all putative regulators of HSL activity. ERK1/2 phosphorylation increased at 3 min in CON and EX+ADR. Because HSL activity did not increase during exercise when adrenaline was infused prior to exercise (ADR) and because HSL activity increased when adrenaline was infused during exercise (EX+ADR), we conclude that (1) high adrenaline levels can stimulate HSL activity regardless of the metabolic milieu and (2) large increases in adrenaline during exercise, independent of changes in other putative regulators, are able to further stimulate the contraction-induced increase in HSL activity. The results also demonstrate that increased ERK 1/2 phosphorylation coincides with elevated HSL activity, indicating that ERK 1/2 may mediate the contraction-induced increase in HSL activity early in exercise.

Increased adrenocortical and adrenomedullary hormonal activity in 12-year-old children born small for gestational age

Objectives: To determine whether adrenal hormonal activity is altered in children born small for gestational age (SGA), and whether concentrations of adrenal hormones relate to those of serum lipids or to anthropometric measures. Study design: We studied 55 SGA children and 55 appropriate for gestational age (AGA) children at the age of 12 years in a case-control setting. The concentrations of fasting serum cortisol, dehydroepiandrosterone sulfate (DHEAS), plasma epinephrine (E), and norepinephrine (NE) were analyzed. Results: The SGA children had significantly higher mean concentrations of serum DHEAS (3.53 vs 2.89 μmol/L, P =.009) and plasma E (0.33 vs 0.25 nmol/L, P =.005) than their age- and sex-matched control subjects. The mean serum cortisol and plasma NE concentrations did not differ significantly between the groups. However, the SGA children in the highest quartile for serum cortisol had significantly higher concentrations of plasma E (0.50 vs 0.28 nmol/L, P <.001), serum LDL (3.21 vs 2.73 mmol/L, P =.025) and total cholesterol (5.06 vs 4.42 mmol/L, P =.021) than the SGA children in the lower cortisol quartiles. The factors associating with high levels of plasma E in the SGA children were high level of serum cortisol [odds ratio (OR) = 3.8, 95% confidence interval (95% CI) = 1.5-10], LDL cholesterol (OR = 3.9, 95% CI = 1.3-12), male sex (OR = 8.3, 95% CI = 1.0-68) and low birth weight (OR = 1.4, 95% CI = 1.0-1.8) in multiple logistic regression analysis. Conclusions: Twelve-year-old children born SGA had increased DHEAS and epinephrine levels in circulation. High serum cortisol concentrations are associated with high epinephrine, LDL, and total cholesterol levels. (J Pediatr 2002;141:477-82)

Alveolar fluid clearance in late-gestational guinea pigs after labor induction: mechanisms and regulation.

We tested the hypothesis that labor-induced epinephrine release would stimulate alveolar fluid clearance in preterm fetuses. Preterm fetuses were obtained by cesarean section from timed-pregnant guinea pigs at 61-69 days postconception. Fetal guinea pigs were euthanized and placed on continuous positive airway pressure oxygenation, and an isosmolar 5% albumin solution was instilled. Alveolar fluid clearance was measured over 1 h. The fetal lung began to absorb fluid at 64-66 days postconception, and at birth, alveolar fluid clearance quadrupled. Baseline alveolar fluid clearance when present was sensitive to propranolol inhibition and depended on beta-adrenergic stimulation. Measurements of plasma epinephrine in fetal animals confirmed high epinephrine levels in 66- to 69-day postconception fetuses. Prenatal alveolar fluid clearance when present was highly amiloride sensitive, suggesting that amiloride-sensitive Na+ channels were critical. Oxytocin-induced labor initiated an amiloride- and propranolol-sensitive net alveolar fluid clearance in 61-day-gestation animals. Moreover, oxytocin induced significant epinephrine release in all fetuses. These results have clinical implications for infants delivered by cesarean section before the onset of labor. Use of pharmacological agents to induce labor may reduce the occurrence and severity of perinatal respiratory distress.

Adrenergic hyperactivity and metanephrine excess in the nucleus accumbens after prefrontocortical dopamine depletion.

Selective dopamine depletion within the medial prefrontal cortex in rats is known to enhance dopamine and norepinephrine levels in the nucleus accumbens and to induce characteristic behavioral disturbances. The present study was designed to determine levels of adrenaline, apart from dopamine and norepinephrine, and metabolites in the nucleus accumbens after prefrontocortical dopamine depletion. Prefrontocortical dopamine depletion was carried out by injecting 6-hydroxydopamine, and it was validated through: the emergence of behavioral disturbances such as amphetamine-induced stereotypies, spontaneous motor hyperactivity, and enhanced "anxiety-like" responses and through postmortem quantification of catecholamine levels by using high-performance liquid chromatography. The findings indicated that lesioned rats exhibited more oral stereotypies after amphetamine, were hyperlocomotive, and showed more pronounced anxiety-like behaviors than controls. Following prefrontocortical dopamine depletion, postmortem concentrations of dopamine and norepinephrine, along with the metabolites 3,4-dihydroxyphenylacetic acid and vanillylmandelic acid, were reliably enhanced in the nucleus accumbens as expected, and dopamine turnover was decreased. Furthermore the nucleus accumbens contained higher levels of adrenaline and its transmethylated metabolite metanephrine. To sum up, prefrontocortical dopamine depletion induces motor and emotional disturbances in rats and alters the neurochemical profile of the nucleus accumbens, not only inducing dopaminergic and noradrenergic hyperactivity but also leading to adrenaline and metanephrine excess.

Urinary catecholamines and cortisol in recent-onset posttraumatic stress disorder after motor vehicle accidents.

This study examined relationships among stress hormone levels, posttraumatic stress disorder (PTSD) diagnosis and symptoms, and gender shortly after a common civilian trauma. Levels of catecholamines and cortisol in 15-hour urine samples were examined in 55 adults who had been in serious motor vehicle accidents and in 22 age-matched control. Catecholamines were related to PTSD diagnosis and symptoms, but only among men: PTSD-symptomatic men who had been in an accident exhibited elevated levels of epinephrine and norepinephrine 1 month after the accident and had higher epinephrine levels 5 months later. Intrusive thoughts predicted catecholamine levels at 1 month, and avoidance of trauma-relevant stimuli was associated with higher epinephrine levels 5 months later. These effects were not significant among women. Urinary cortisol was also elevated among PTSD-symptomatic men, but not women, and only immediately (1 month) after the accident. For men and women, greater emotional numbing predicted a lower cortisol level 6 months after the accident. These findings were interpreted as limited support for the generalizability of findings in men with chronic, combat-related PTSD and indicate the need for additional research on psychoendocrine assessment of traumatized women and specific dimensions of PTSD symptomatology.

Activation of haemostasis by exercise, mental stress and adrenaline: effects on platelet sensitivity to thrombin and thrombin generation

Stress-induced activation of haemostasis may be involved in the triggering of acute coronary syndromes. We compared the effects of mental stress, dynamic exercise and adrenaline infusion on platelet sensitivity to thrombin using flow-cytometric analysis of platelet fibrinogen binding in whole blood, and platelet aggregability using filtragometry ex vivo, in healthy volunteers. Furthermore, we assessed thrombin generation [prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes in plasma] and thrombin activity (fibrinopeptide A in plasma). Exercise (bicycle ergometry) enhanced thrombin-induced platelet fibrinogen binding (P<0.05) and platelet aggregability (P<0.01), and elevated F1+2, thrombin-antithrombin complexes and fibrinopeptide A (P<0.05 for all three). Adrenaline infusion enhanced thrombin-induced platelet fibrinogen binding and platelet aggregability (P<0.05), and elevated thrombin-antithrombin complexes (P<0.05), whereas F1+2 and fibrinopeptide A levels were not significantly affected. Mental stress increased platelet sensitivity to high concentrations of thrombin only, and produced small increases in levels of thrombin-antithrombin complexes. Time control experiments showed no important changes with repeated measurements during rest. Platelet responses to exercise and adrenaline were reversible, with recovery 60 min later. Thus, heavy exercise and high levels of adrenaline reversibly increased platelet aggregability and platelet sensitivity to thrombin, and enhanced thrombin formation; the effects were most pronounced during exercise. Mental stress only weakly affected these parameters.

The sarcoplasmic reticulum plays a major role in isometric contraction in atrial muscle of yellowfin tuna

We used an isometric muscle preparation to test the hypothesis that yellowfin tuna Thunnus albacares utilize the intracellular Ca2+ storage sites of the sarcoplasmic reticulum (SR) during routine contractions. Ryanodine (a blocker of SR Ca2+ release) reduced the force of contraction by approximately 50 % and the rates of contraction and relaxation by 60 % in yellowfin tuna atrium. High levels of adrenaline were unable to ameliorate the effects of ryanodine. We conclude that the SR is active in contributing Ca2+ to force development at physiological contraction frequencies. Further, we suggest that, by using intracellular Ca2+ cycling, the yellowfin tuna is able to increase the maximum contraction frequency of its cardiac muscle beyond that of most other fishes.

The systemic stress response to thermal injury in children

Thermal injury is extremely stressful, but data characterizing the endocrine stress response to this injury in children are sparse. The objective of this study was to measure the effects of thermal injury on the levels of stress hormones in children and to assess the temporal changes associated with them. Twenty-three children, 13 girls and 10 boys aged between 5 months and 12 years 3 months (mean, 2 years 11 months), with burns covering 10-61% of their body surface (mean, 20.5%) were studied during the first 5 days following injury. The levels of arginine vasopressin, angiotensin II, cortisol, adrenaline, noradrenaline and dopamine were measured in sequential blood samples obtained from thermally injured children on admission and at specified time intervals during the 5 days of the investigation. At admission the concentrations of all the hormones were high, and varied widely between individual patients. The geometric mean and 95% confidence intervals of admission hormone levels were as follows: arginine vasopressin 18.3 (8.3-40.7) pmol/l; angiotensin II 122.0 (56.0-266.2) pmol/l; cortisol 650.6 (473.0-895.0) nmol/l; dopamine 1.0 (0.1-8.0) nmol/l; adrenaline 6.4 (3.2-12.5) nmol/l and noradrenaline 2.3 (1.3-4.3) nmol/l. Although the concentrations of arginine vasopressin and cortisol returned to normal 24 to 36 h after admission, the levels of angiotensin II, adrenaline and dopamine fluctuated and remained higher than normal throughout the study (108 h). Thermal injury results in the release of abnormally high levels of stress hormones in children. Although there are similarities between some of the data reported here and those reported in adults, higher levels of adrenaline and lower levels of noradrenaline than reported in adults suggest important differences too. These differences may need to be taken into account in the management of burn-injured children.

Mechanical properties of human saphenous veins from normotensive and hypertensive patients

Background. Different reactivities of saphenous vein grafts in hypertensive and normotensive patients could lead to differences in the postoperative patency of the grafts. Methods. In saphenous vein rings isolated from remnants of aorta-coronary grafts obtained from hypertensive and normotensive patients we studied the length-tension relationship; response to high levels of potassium, norepinephrine, and epinephrine; and relaxation in response to calcium deprivation. Results. The rings from hypertensive patients were stiffer and developed more force (grams force/grams weight) than the rings from normotensive subjects to 80 mmol/L potassium (59 ± 16 versus 25 ± 5, p < 0.05) and to 1 μmol/L norepinephrine (61 ± 8 versus 36 ± 7, p < 0.05), but not to 10 μmol/L epinephrine (57 ± 11 and 54 ± 11; not significant). The rings from hypertensive patients relaxed more slowly than those of the normotensive subjects in a calcium-free medium (time to half-relaxation of 976 ± 180 versus 548 ± 81 seconds; p < 0.05). Conclusions. The saphenous vein from hypertensive patients is less distensible, slower to relax, and more reactive to at least two agonists. These differences could influence the graft’s patency and the clinical outcome.

Alpha-adrenoreceptor influences on liquid movements by in vitro lungs from fetal guinea pigs.

Lungs from near-term fetal guinea pigs (60 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye-dilution method. Studies of 30 fetuses showed that untreated preparations produced fluid at 1.34 +/- 0.21 ml.h-1.kg body wt-1, but epinephrine at concentrations known at delivery (10(-8) and 10(-7) M) produced significant reductions or fluid reabsorption (analysis of variance, regression analysis); at high levels (10(-6) and 10(-5) M, epinephrine had no effect. Maximal responses from 10(-7) M epinephrine involved alpha-adrenoreceptors, since they were abolished by 10(-6) M phentolamine (alpha-antagonist) but were unaffected by 10(-6) M propranolol (beta-antagonist; n = 36). Activation was through alpha2-adrenoreceptors, since responses were abolished by 10(-4) M yohimbine (alpha-antagonist; n = 24) but were resistant to 10(-5) M prazosin (alpha 1-antagonist; n = 24). At high levels of epinephrine (10(-5) M), where responses did not normally occur, reductions in lung liquid production were large if prazosin was also present (n = 24), and increases were significant if yohimbine was included (n = 24). In guinea pigs, epinephrine appears to activate lung fluid reabsorption through alpha 2-adrenoreceptors; at high concentrations only, it can also increase production through alpha 1-adrenoreceptors. Therefore, species differences appear to exist.

Different humoral responses during head-up tilt testing among patients with neurocardiogenic syncope

Neurocardiogenic dysfunction is believed to result from activation of ventricular mechanoreceptors. To asses other humoral and circulatory mechanisms activated during vasovagal syncope, epinephrine, norepinephrine, renin, and aldosterone levels were measured during head-up tilt testing. Twenty-three patients referred because of vasovagal syncope underwent passive head-up tilt testing (80 degrees). Blood samples were taken at baseline, after 30 minutes of supine rest and at syncope. Five patients (four men, one woman; mean age 46 ± 27 years) had cardioinhibitory syncope. Seven patients (five men, two women; mean age 40 ± 12 years) had vasodepressor syncope. Eleven patients (eight men, three women; mean age 55 ± 21 years) had negative results of head-up tilt tests. Among patients with cardioinhibitory syncope, norepinephrine concentration rose significantly from baseline to syncope (0.44 ± 0.12 ng/ml versus 1.14 ± 0.72 ng/ml; p < 0.05), whereas no significant change was observed in epinephrine (0.08 ± 0.03 ng/ml versus 2.74 ± 2.85 ng/ml; p = not significant [NS]), renin (5.68 ± 3.03 pg/ml versus 19.58 ± 11.47 pg/ml; p = NS), or aldosterone concentration (66.60 ± 16.10 ng/ml versus 109.00 ± 44.70 ng/ml; p = NS). Patients with vasodepressor syncope had a significant rise in renin (9.03 ± 4.56 pg/ml versus 52.53 ± 41.63 pg/ml; p < 0.05) and aldosterone concentration (95.43 ± 103.03 ng/ml versus 249.57 ± 191.54 ng/ml; p < 0.05), whereas no change in level of epinephrine (0.12 ± 0.12 ng/ml versus 0.28 ± 0.33 ng/ml; p = NS) or norepinephrine (0.60 ± 0.26 ng/ml versus 0.86 ± 0.53 ng/ml; p = NS) was detected. Among patients with negative results of tilt tests, levels of renin (7.94 ± 7.19 pg/ml versus 27.71 ± 18.50 pg/ml; p < 0.01) and aldosterone (64.64 ± 28.33 ng/ml versus 160.91 ± 79.58 ng/ml; p < 0.01) rose significantly, whereas no change was seen in epinephrine (0.12 ± 0.14 ng/ml versus 0.23 ± 0.31; p = NS) or norepinephrine concentration (0.54 ± 0.21 ng/ml versus 0.82 ± 0.52; p = NS). Patients with cardioinhibitory syncope were characterized by a rise in norepinephrine level and blunted activation of the renin-angiotensin-aldosterone axis at syncope. Unlike patients with cardioinhibitory syncope, the renin-angiotensin-aldosterone axis is activated in patients with vasodepressor syncope and patients with a negative result of head-up tilt test without a statistically significant increase in catecholamine levels. Patients with cardioinhibitory syncope have higher epinephrine levels at syncope compared with patients with a negative result of head-up tilt test and patients with vasodepressor syncope. (Am Heart J 1998;135:67-73.)

Central Monoamines in Free-Ranging Lizards: Differences Associated with Social Roles and Territoriality

During the breeding season different social classes of field-active lizards, Sceloporus jarrovi, exhibit regionally specific changes in central monoaminergic activation. Changes in serotonergic content and turnover between lizards from different social classes are seen in forebrain structures (telencephalon and diencephalon) and reflect events associated with reproductive behaviors, stress and aggression. Males without territories (satellite males) exhibit higher forebrain serotonin (5-HT) system activation compared to territorial males and adult females. This serotonergic activation includes increased 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio, suggesting increased release and catabolism. Satellite males also exhibit higher 5-HIAA/5-HT ratios (serotonergic turnover) compared to territorial males following agonistic interactions. Territorial males, immediately following aggressive defense of territories against intruder males, exhibit increased 5-hydroxytryptophan (5-HTP) levels, higher 5-HIAA levels and 5-HIAA/5-HT ratio, higher epinephrine levels, greater MHPG/NE, more DOPAC and larger DOPAC/DA ratio compared to territorial males that did not have an aggressive encounter. These differences suggest activation of 5-HT, norepinephrine (NE), and dopamine (DA) systems by the synthesis and release of more 5-HT and the release of more NE and DA during aggressive defense of territory. The highest activity of serotonergic systems is exhibited by satellite males compared to territorial males, perhaps reflecting stress in subordinate animals from social and ecological sources.

P-593 - Alteration of epinephrine and norepinephrine levels in myocardial interstitium of papillary muscle by infusion of high levels of epinephrine or norepinephrine

P-593 - Alteration of epinephrine and norepinephrine levels in myocardial interstitium of papillary muscle by infusion of high levels of epinephrine or norepinephrine

Effect of caffeine on recognition of and physiological responses to hypoglycaemia in insulin-dependent diabetes

SummaryBackground For the patient with diabetes, hypoglycaemia unawareness—ie, the warning signs of falling blood glucose are missing—is potentially dangerous. One study has suggested that, in healthy volunteers, caffeine might be a helpful treatment. Our study looked at two effects of caffeine ingestion (250 mg) on the brain—namely, a decrease in cerebral blood flow and an increase in brain glucose use—to see if the recognition of and physiological responses to hypoglycaemia were altered in patients with insulin-dependent diabetes mellitus (IDDM).Methods 12 patients were studied twice. A hyperinsulinaemic glucose clamp was used to maintain plasma glucose at 5 mmol/L for 90 min, followed by 60 min at 3·8 mmol/L, and then 2·8 mmol/L for a further hour. After 30 min at 5 mmol/L, patients consumed, in a double-blind, crossover design, 250 mg caffeine or matched placebo. We recorded middle cerebral artery velocity (VMCA), counterregulatory hormone levels, and cognitive function, and patients recorded hypoglycaemia symptoms on a visual analogue scale.Results Caffeine caused an immediate and sustained fall in VMCA of 10 cm/s, from 60 to 50 cm/s (95% Cl -5 to -15 cm/s; p<0·001). At a blood glucose of 3·8 mmol/L, plasma adrenaline levels were twice as high after caffeine than after placebo (difference 524 pmol/L). When glucose was lowered to 2·8 mmol/L, caffeine ingestion was associated with: greater awareness of hypoglycaemia in 9 patients, significantly more intense autonomic and neuroglycopenic symptoms, and higher levels of adrenaline, cortisol, and growth hormone. Cognitive function (latency of P300 evoked potentials) deteriorated to the same extent in both studies at this glucose level.Interpretation The sustained fall in VMCA and augmented sympathoadrenal and symptomatic responses during moderate hypoglycaemia suggest caffeine as a potentially useful treatment for diabetic patients who have difficulty recognising the onset of hypoglycaemia.

High physiological levels of epinephrine do not enhance muscle glycogenolysis during tetanic stimulation

This study examined whether high physiological concentrations of epinephrine (EPI) would enhance muscle glycogenolysis during intense muscular contractions. Muscles of the rat hindlimb were perfused for 12 min at rest and 45 s of tetanic stimulation (1.0-Hz train rate, 100-ms train duration at 80 Hz) without EPI (control) or with 15 or 35 nM EPI. In the EPI groups the muscles were perfused with EPI for the last 2 min of rest perfusion and throughout stimulation. Glycogenolysis in the white gastrocnemius, red gastrocnemius, plantaris, and soleus muscles during stimulation was unaffected by the presence of EPI in the perfusion medium. In addition, muscle lactate and hindlimb lactate efflux were similar in EPI and control groups. It is concluded that EPI is not important for enhancing glycogenolysis in rat muscles composed predominantly of fast-twitch fibers during intense short-term tetanic stimulation.