Measurement Of Plasma Catecholamines Research Articles

Enhanced cardiac metabolism of plasma glucose in high-altitude natives: adaptation against chronic hypoxia

The metabolism of glucose in mammalian heart is 25-50% more O2 efficient than the metabolism of free fatty acids. To assess the role of substrate preference in adaptations to chronic hypoxia, positron emission tomographic measurements of heart regional glucose uptake rates after an overnight fast were made in volunteer Quechua subjects and in Sherpa subjects, both indigenous to altitudes of over 3,000 m, and in a group of lowlander volunteers. Highest uptake rates were found in the Quechuas on arrival and in the Sherpas after a 3-wk period at low altitude, intermediate rates in Quechuas after a 3-wk period at low altitude and in the lowlanders, and lowest rates in Sherpas on arrival. These low values were probably related to the stress of travel to the site of the experiments. Measured plasma catecholamines, hormones, and substrates indicated that glucose concentrations correlated best with observed variations in glucose uptake, with a negative correlation for the control subjects and a positive correlation for the Quechuas and Sherpas. Uptake values in Quechuas declined significantly after a 3-wk period at low altitude, but the positive correlation with glucose levels persisted. We conclude that an elevated glucose preference in heart is a true metabolic adaptation in humans adapted over generations to chronic hypoxia.

Catecholamines and Diabetic Autonomic Neuropathy

In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy.

State of the sympathoadrenal system in patients with traumatic injury to the spinal cord

Measurement of plasma catecholamines (epinephrine, norepinephrine, and dopamine) by the method of high-performance liquid chromatography showed significantly elevated epinephrine levels in patients with spinal and spinal cord trauma as compared to healthy donors and patients with craniocerebral trauma. The neuroendocrine abnormalities detected in patients with traumatic disease of the spinal cord aggravated this disease. The elevated blood level of epinephrine, which is a sign of heightened activity of the sympathoadrenal system, points to an important role of neurotransmitters in the establishment of a pathological state in traumatic injuries to the vertebral column and spinal cord.

Effects of β-adrenergic blockade on vasodepressor reaction in patients with vasodepressor syncope

The mechanism of vasodepressor reaction induced by head-up tilt test in patients with vasodepressor syncope is not clearly understood. We hypothesized that an abnormal alteration of β-adrenergic transmission could be involved in these patients. We measured plasma catecholamine concentration during tilt and density of β-adrenoceptors and tested the effects of β-adrenergic blockers in the prevention of the vasodepressor reaction in patients with vasodepressor syncope. Ten patients had reproducibly induced vasodepressor syncope (mean 3.1 ± 0.3 episodes in each patient) with head-up tilt (80 degrees) for 10 minutes with isoproterenol infusion (1 to 3 μg/min). Syncope occurred at 6.3 ± 1.7 minutes during tilt with isoproterenol infusion. The plasma norepinephrine concentration before administration of β-blocker was significantly elevated during tilt compared to the supine position (0.347 ± 0.079 ng/ml in supine position with isoproterenol vs 0.468 ± 0.082 ng/ml at 3 minutes of tilt, p < 0.001, and vs 0.503 ± 0.106 ng/ ml at the onset of vasodepressor reaction, p < 0.005; n = 8). Plasma norepinephrine after administration of the selective β 1-adrenergic blocker metoprolol (40 mg/day) was similarly elevated (0.282 ± 0.071 ng/ml in supine position with isoproterenol vs 0.390 ± 0.078 ng/ml at 3 minutes of tilt, p < 0.05, n = 6; and vs 0.547 ± 0.152 ng/ml at the onset of vasodepressor reaction, p < 0.001, n = 3). Plasma norepinephrine after administration of the nonselective β-blocker propranolol (30 mg/day) was not significantly elevated (0.254 ± 0.063 ng/ml in supine position with isoproterenol vs 0.339 ± 0.081 ng/ml at 3 minutes of tilt, p not significant; and vs 0.343 ± 0.079 ng/ml at 10 minutes of tilt, p not significant, n = 6). Metoprolol prevented vasodepressor syncope in 5 of 10 patients; propranolol prevented syncope in all 10 patients ( p < 0.05). Heart rate after administration of propranolol did not increase in either the supine position with isoproterenol or during tilt compared to control tilt and tilt after administration of metoprolol. We abserved no significant differences in the number and afrinity of β-adrenoceptors between five patients with vasodepressor syncope and tive age-matched normal subjects. We conclude that propranolol is far more useful for the prevention of vasodepressor syncope than metoprolol. Our data suggest that β 2-adrenergic transmission may play an important role in the induction of vasodepressor reaction in patients with vasodepressor syncope.

New approaches to evaluate sympathoadrenal system activity in experiments on Earth and in space

In previous studies the activity of the sympathoadrenal system (SAS) in cosmonauts during space flights was evaluated by measuring plasma catecholamines (CA) levels and urinary CA and their metabolites concentrations. Plasma CA levels are accepted indicators of SAS activity, however, they are determined by the plasma clearances as well as the rates of CA release (spillover-SO) into the bloodstream. Nowadays methods are available which evaluate not only plasma levels of CA but also their release, spillover, uptake, reuptake, degradation and also CA synthesis in vivo measured by plasma levels of dihydroxyphenylalanine (DOPA). Plasma concentrations of DOPA, the CA noradrenaline (NE), adrenaline (ADR), and dopamine (DA), the deaminated catechol metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC), and the O-methylated metabolites methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured during immobilization stress (IMO) in conscious rats. Radiotracer methods were used to measure NE SO. IMO markedly increased arterial NE levels but NE SO was less elevated bacause the NE clearance was slightly reduced in IMO rats. Simultaneous measurements of plasma CA and their metabolites provide another means to obtain information about SAS function. For instance, dissociation between changes of plasma DHPG and NE levels can indicate changes in neuronal reuptake of NE. We found marked parallel increases in plasma NE and DHPG levels during acute IMO; however after repeated IMO, plasma NE levels were increased but DHPG responses were less pronounced suggesting a reduced NE reuptake. DOPA, the CA precursor, circulates in plasma at a concentration higher than NE. During stress, increased sympathoneural outflow stimulates DOPA synthesis and release into the circulation supporting the view that changes in plasma DOPA levels during stress reflect in vivo changes in the rate of CA synthesis. We propose to measure the new plasma indicators of SAS activity in cosmonauts and/or in animals before, during and after space flights.

Sympathoinhibition by rilmenidine in conscious rabbits: involvement of ?2-adrenoceptors

Cardiovascular and sympathetic nervous system effects of the mixed alpha 2-adrenoceptor and imidazoline receptor agonist rilmenidine were studied in conscious rabbits chronically instrumented for the recording of the firing rate of renal sympathetic fibers. Separate experiments were carried out on pithed rabbits with electrically stimulated (2 Hz) sympathetic outflow. Drugs were administered intravenously in a cumulative manner. In conscious rabbits, rilmenidine 0.1, 0.3 and 1.0 mg kg-1 dose-dependently lowered blood pressure, renal sympathetic nerve activity, heart rate and the plasma concentration of noradrenaline and adrenaline. The effect on blood pressure and plasma catecholamines was maximal after 0.3 mg kg-1 whereas heart rate and renal sympathetic nerve activity decreased further after rilmenidine 1.0 mg kg-1. Yohimbine 0.1 and 0.5 mg kg-1, when injected subsequently, attenuated and at the higher dose abolished all effects of rilmenidine. The effects of rilmenidine were also antagonized by the alpha 2-adrenoceptor antagonist 2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1H-imid azole HCl (RX821002; 0.1 and 0.5 mg kg-1). Yohimbine 0.1 and 0.5 mg kg-1 did not attenuate or attenuated only slightly the decrease of heart rate and renal sympathetic nerve activity produced by infusion of vasopressin. In pithed rabbits with electrically-stimulated sympathetic outflow, yohimbine 0.1 submaximally and yohimbine 0.5 mg kg-1 maximally increased the plasma noradrenaline concentration. The experiments show by direct measurement of sympathetic nerve firing and plasma catecholamines that rilmenidine causes sympathoinhibition in conscious rabbits, presumably through central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)

Breakdown of 3,4-dihydroxybenzylamine and dopamine in plasma of various animal species by semicarbazide-sensitive amine oxidase

We report a rapid breakdown of dopamine and especially of 3,4-dihydroxybenzylamine, the frequently-used internal standard in catecholamine determinations, in plasma of many but not all animal species. Species investigated were cow, sheep, goat, pig, horse, rabbit, dog, guinea pig, mouse, chicken, rat and man. In some species 3,4-dihydroxybenzylamine nearly completely disappeared at 4°C within 15 min after addition to the plasma. Added dopamine, but not norepinephrine and epinephrine, also rapidly disappeared at 4°C. Disappearance rates were increased at higher temperatures, and at 20°C also norepinephrine showed some breakdown. The breakdown is caused by a semicarbazide-sensitive amine oxidase in the plasma, and can be completely blocked by the addition of the inhibitor semicarbazide. Measurement of plasma catecholamine concentrations in animal species can thus lead to erroneous results, especially when 3,4-dihydroxybenzylamine is used as an internal standard. Only when blood is collected in tubes containing an inhibitor of semicarbazide-sensitive amine oxidase like semicarbazide can reliable plasma catecholamine measurements be performed.

Effects of Ibopamine on Postural Hypotension in Pure Autonomie Failure

We wished to determine whether ibopamine, a dopaminergic prodrug with weak agonist activity on alpha- and beta-adrenoceptors, improves orthostatic tolerance in autonomic insufficiency. Three subjects with severe orthostatic hypotension resulting from pure autonomic failure (PAF) were studied. Direct arterial blood pressure (ABP) and heart rate (HR) were recorded continuously. Orthostatic tolerance was evaluated by 60 degrees passive head-up tilting. Tilting was performed before and after a single oral 100-mg dose of ibopamine. Blood samples for measurement of plasma catecholamines, free epinine (the active metabolite of ibopamine), and conjugated epinine were taken at regular intervals. In all 3 subjects, orthostatic tolerance was greatly improved by ibopamine. This improvement occurred as soon as 10-30 min after administration of ibopamine and lasted 20-50 min. alpha-Adrenoceptor blockade with phentolamine abolished the effect of ibopamine. The interindividual pharmacokinetics of ibopamine varied considerably: Peak plasma concentrations of ibopamine in the three subjects were 2.8, 4.5, and 35.4 ng/ml, respectively. The high level of epinine in one patient was associated with severe hypertension and tachycardia. Ibopamine may be a valuable new pharmacologic treatment for orthostatic hypotension in PAF, but in light of the highly variable interindividual pharmacokinetics further studies must be performed before use of the compound can be advocated in this disorder.

Pressor hormone profile during stress in hypertension: does vasopressin interfere with left ventricular hypertrophy?

Neurohormonal factors may account for the fact that patients with similar severity and duration of hypertension develop different degrees of left ventricular hypertrophy (LVH). The purpose of this work was to compare the pressor hormone profiles of hypertensive subjects off medication during exercise testing. Nineteen patients, stratified according to echocardiographically diagnosed absence (Group I n = 6) or presence (Group II n = 13) of LVH, underwent testing on the treadmill according to the Bruce protocol. Both groups were comparable in age, severity and duration of hypertension and reached similar double product at peak exercise. Measurements of plasma renin activity (PRA), plasma catecholamines and vasopressin (AVP) at baseline, peak exercise and post exercise revealed significant differences between groups: Group I had suppressed PRA levels throughout and had significantly higher baseline AVP levels, which increased further at peak effort. Group II had significantly higher baseline PRA levels, which tended to increase further at peak effort, and had suppressed AVP levels throughout. There was a significant negative correlation between percent increments in AVP and increments in double product. Norepinephrine increased significantly with effort in both groups, but the levels attained were higher in Group I. In view of the known negative inotropic action of AVP and the trophic effect of angiotensin, we speculate that lower baseline AVP and higher PRA, together with inability of AVP to increase with effort, may be causally related to development of LVH.

Adrenaline and noradrenaline responses during insulin-induced hypoglycaemia in man: should the hormone levels be measured in arterialized venous blood?

To compare arterial, arterialized venous and venous measurements of plasma catecholamines during hypoglycaemia, six healthy men were studied by an iv infusion of insulin (1034 pmol.kg-1.h-1). Arterial blood glucose was clamped at the baseline level for the first 30 min and then reduced to 3.2 and to 2.5 mmol/l for 20 min subsequently. At each stage, arterial, arterialized venous and venous blood samples were simultaneously taken for analyses of plasma catecholamines. Plasma glucagon significantly declined during hyperinsulinaemic euglycaemia and then increased during hypoglycaemia. Plasma adrenaline and noradrenaline increased significantly during hypoglycaemia. During euglycaemia and mild hypoglycaemia, arterial adrenaline tended to be higher and arterial noradrenaline lower as compared with the corresponding arterialized and venous values. During marked hypoglycaemia, the arterial catecholamines were significantly higher than that of the two venous samples (p < 0.05). There was a significant correlation between the arterial and the arterialized as well as venous catecholamine values (p < 0.005). We conclude that, during euglycaemia and mild hypoglycaemia, the arterialized adrenaline values are closer to the arterial levels whereas the arterialized noradrenaline concentrations are similar to those measured in venous blood. However, during marked hypoglycaemia, both the arterialized adrenaline and noradrenaline are 20-30% lower than the arterial values, being close to the venous levels.

Blood pressure, heart rate and catecholamine response during fiberoptic nasotracheal intubation under general anesthesia.

Arterial blood pressure (ABP) and heart rate were recorded at one-minute intervals during several stages of intubation in the fiberscope group and the laryngoscope group, to determine if fiberoptic nasotracheal intubation would result in fewer hemodynamic and catecholamine responses than when intubation was performed with a Macintosh laryngoscope. Blood samples were also taken to measure plasma catecholamine concentration immediately after intubation with the fiberscope. The mean ABP in the laryngoscope group was slightly greater than that of the fiberscope group for 4 min after intubation. Heart rates at 2 min and 4 min after intubation in the laryngoscope group were significantly greater than those for the fiberscope group. Even immediately after intubation, the mean plasma levels of epinephrine and norepinephrine were unchanged in the fiberscope group. Arterial oxygen saturation (Sp(O)(2)) was maintained within normal range during both of intubation procedures, although the time required for intubation was longer than in the laryngoscope group. Other cardiovascular complications were more common in the laryngoscope group than in the fiberscope group. These results suggest that fiberoptic intubation results in less severe stress than does laryngoscopic intubation. Fiberoptic intubation should therefore be used not only in patients with difficult airway, hypertension, ischemic heart disease, or cerebrovascular atherosclerosis, but also it is recommended for all patients for whom nasotracheal intubation is indicated.

Delayed Orthostatic Intolerance

In seven patients who presented with lightheadedness, fatigue, "weakness," and sometimes syncope, blood pressure was found not to fall after standing for 3 to 4 minutes but to fall severely, frequently with syncope or presyncopal symptoms, after 13 to 30 minutes when measured every minute with an automatic device. This delayed orthostatic hypotension could be corrected with inflation of a pressure suit to 45 mm Hg. Its mechanism was further investigated with measurements of plasma catecholamines, plasma cortisol and aldosterone responses to corticotropin, and the effects of norepinephrine infusions on blood pressure and venous contractility. There was normal or excessive orthostatic norepinephrine release in all patients, evidence of impaired venous innervation in the legs in some, and various disorders in the other patients. Since therapeutic improvement in the orthostatic hypotension greatly reduced the symptoms, we concluded that orthostatic hypotension occurring after more than 10 minutes of standing is a potentially debilitating and often correctable disorder.

Plasma catecholamine concentrations after successful resuscitation in patients.

To measure plasma catecholamine concentrations after cardiopulmonary resuscitation (CPR) and to correlate catecholamine concentrations with heart rate (HR), BP, and plasma glucose and lactate concentrations. Prospective, descriptive study. Emergency medical service at a University Hospital. Ten patients (58 to 85 yrs) with out-of-hospital cardiac arrest. At 1, 5, 15, 30, and 60 mins after restoration of spontaneous circulation, blood samples were drawn and BP and HR were measured. Plasma catecholamine concentrations were measured by high-pressure liquid chromatography and plasma glucose and lactate concentrations were measured by enzymatic methods. Median plasma epinephrine and norepinephrine concentrations were 136.3 micrograms/L (136,300 pg/mL), range 27.6 to 397.6 micrograms/L (27,600 to 397,600 pg/mL), and 4.7 micrograms/L (4700 pg/mL), range 1.8 to 14.5 micrograms/L (1800 to 14,500 pg/mL), respectively, at 1 min. Median plasma epinephrine and norepinephrine concentrations decreased to 8.7 micrograms/L (8700 pg/mL), range 1.2 to 55.0 micrograms/L (1200 to 55,000 pg/mL) and 1.9 micrograms/L (1900 pg/mL), range 1.3 to 5.8 micrograms/L (1300 to 5800 pg/mL), respectively, at 60 mins after restoration of spontaneous circulation. Epinephrine concentrations decayed with a semilogarithmic decay pattern. The half-life for the alpha phase was 2.2 mins and was 38.7 mins for the beta phase. Mean values of systolic arterial pressure were between 136 +/- 23 mm Hg at 1 min and 120 +/- 15 mm Hg at 30 mins. Median plasma glucose concentrations were between 8.2 mmol/L (147.7 mg/dL; range 5.8 to 11.2 mmol/L [104.5 to 201.8 mg/dL]) at 1 min and 13.9 mmol/L (250.4 mg/dL; range 9.7 to 16.6 mmol/L [174.8 to 299.1 mg/dL]) at 30 mins. Lactate values were between 11.4 mmol/L (range 4.7 to 16.5) at 1 min and 5.2 mmol/L (range 2.7 to 12.5) at 60 mins. No significant correlations were found between circulating catecholamine concentrations and the other variables. After CPR, plasma catecholamine concentrations remained at high values but they did not lead to increases in BP, HR, or circulating glucose concentrations.

Plasma catecholamine levels after intraosseous epinephrine administration in a cardiac arrest model

To measure plasma catecholamine levels and the cardiovascular response after administering epinephrine by the intraosseous (IO) route in an animal cardiac arrest model. Eighteen anesthetized swine (weight, 12 to 15 kg) subjected to five minutes of electrically induced ventricular fibrillation followed by 25 minutes of chest compression and ventilation. Animals were anesthetized with 30 mg/kg IM ketamine and 75 mg/kg IV a-chloralose, intubated, placed on a respirator, and surgically instrumented. Ventricular fibrillation was induced. After five minutes of cardiac arrest, mechanical chest compressions were initiated and continued until the end of the experiment. Animals received 0.01 mg/kg IO epinephrine (five) or 0.1 mg/kg IO epinephrine (five) at ten and 20 minutes. The eight controls did not receive epinephrine. Plasma epinephrine levels increased from 1.0 to approximately 40 to 85 ng/mL with the initiation of CPR. Epinephrine (0.01 mg/kg) increased plasma epinephrine levels to 222 +/- 72 ng/mL at 12 minutes after arrest but did not increase diastolic or mean blood pressure. Epinephrine (0.1 mg/kg) increased plasma epinephrine levels to 1,103 +/- 157 ng/mL at 12 minutes after arrest and increased diastolic and mean arterial blood pressures. IO epinephrine is rapidly transported to the central circulation but requires larger than currently recommended doses to produce a significant change in blood pressure.

Determinants of subsequent late postoperative left ventricular function and reversal of ventricular dilatation after mitral valve replacement for chronic mitral regurgitation.

We studied 16 patients with chronic mitral regurgitation by echocardiography before, and at 3 weeks, at 6-8 months and at 1-9 years after mitral valve replacement (MVR) to investigate serial changes in left ventricular (LV) function and reversal of ventricular dilatation. All patients at an average of 2.6 years after, and 8 patients before MVR were also studied by echocardiography and, except for 3 patients by measuring plasma catecholamines from the right atrium during bicycle exercise. Before operation, all patients were divided into group A (n = 12) with end-systolic dimension (ESD) < 4 cm and systolic blood pressure (SBP)/ESD > 3, and group B (n = 4) with ESD > 4 cm and SBP/ESD < 3. Maximum reduction in end-diastolic dimension (EDD) occurred at 3 weeks in all patients after MVR (from 60.5 +/- 3.7 to 49.0 +/- 4.5 mm, p < 0.05). ESD was reduced significantly (p < 0.5) only in group A. LV function was normal in group A, but it was depressed in group B at early and late periods after MVR. The slopes of the relationship between the mean velocity of circumferential fiber shortening (Vcf) and plasma norepinephrine (NE) during exercise in all patients in group B decreased along with the depression in LV function. After operation, all patients in group A reached New York Heart Association (NYHA) functional class I, while patients in group B were in NYHA class II. It is concluded that the surgical outcome after MVR for chronic MR will be better if preoperative ESD < 4 cm and SBP/ESD > 3. The relationship between mean Vcf and plasma NE during exercise seemed to be a useful index to evaluate the inotropic reserve of the LV.

Pheochromocytoma in a Long-Term Hemodialysis Patient

A right adrenal tumor was found incidentally by renal echography in a 25-year-old man, who had been on hemodialysis for 4 years. Inquiry and clinical examination suggested pheochromocytoma, which was confirmed by plasma catecholamine measurements. Subsequent adrenalectomy was uneventful. Although hypertension, headache, and diaphoresis are common symptoms in a dialyzed patient, pheochromocytoma has to be eliminated in the presence of this clinical triad.

Measurement of plasma catecholamines by high-performance liquid chromatography with electrochemical detection in intensive care patients after dobutamine infusion

A procedure for the determination of plasma catecholamine concentrations in critical care patients after dobutamine infusion is presented. A modified chromatographic system is required with an additional washing procedure to achieve maximum sensitivity and stable chromatographic conditions. The influence of storage time on the catecholamine concentrations of plasma samples is reported in detail. A time-dependent decrease in catecholamine concentrations of up to 12 and 39% was found within two and ten months, respectively.

Comparison of two doses of endotracheal epinephrine in a cardiac arrest model

The objective of this study was to measure plasma catecholamine levels and the cardiovascular response before and after endotracheal administration of epinephrine in a swine cardiac arrest model. Prospective, controlled laboratory investigation. Twenty-one swine weighing 10 to 12 kg, anesthetized with ketamine and alpha-chloralose and ventilated with room air. Ventricular fibrillation was induced with 90 V of 60 Hz current delivered to the right ventricle by transvenous pacemaker. Blood samples for epinephrine were drawn before arrest and every two minutes thereafter. At five minutes, external mechanical cardiac compressions were initiated. Nine animals received no further therapy and served as controls. Two groups of six animals received either 0.01 mg/kg or 0.1 mg/kg of epinephrine through the endotracheal tube at ten and 20 minutes. Blood samples were assayed for epinephrine. Arterial blood pressure, lead II ECG, and plasma epinephrine. Swine receiving epinephrine 0.01 mg/kg had an increase in epinephrine levels after drug administration, but these were not significantly different from control levels. The 0.1-mg/kg dose group had a significant increase in plasma epinephrine levels compared with controls and the 0.01-mg/kg dose group after receiving epinephrine at ten and 20 minutes. These increases were from 14 +/- 3 to 215 +/- 40 ng/mL (+/- SEM) at 12 minutes after arrest and from 151 +/- 56 to 402 +/- 80 ng/mL at 22 minutes after arrest. These data suggest that standard dosing of epinephrine through the endotracheal tube during arrest does not produce significant increases in plasma catecholamines or blood pressure. Epinephrine 0.1 mg/kg produces a significant increase in plasma epinephrine levels, but it is not sufficient to produce a significant change in blood pressure.

Sympathoadrenal activity and hypoglycemia in the hibernating garden dormouse

The hibernating garden dormouse is spontaneously hypophagic during the prehibernating period at which time we found a low peripheral sympathetic activity (S.A.). The aim of this work was to investigate the link between dietary intake and S.A. The S.A. was evaluated by measurement of catecholamines in both plasma and adrenal glands by HPLC. Food intake, body weight, energy expenditure and plasma glucose were measured during the reentry phase of the hibernating period. The following results were obtained: the energy intake in pretorpid animals (55 to 83 kJ/24 h/100 g body weight) was less than energy expenditure which was between 145 and 97 kJ/24 h/100 g. The energy deficit induces marked hypoglycemia immediately before the onset of hypothermia (117 mg/dl vs. 76 mg/dl) and leads to a drastic drop in the peripheral sympathetic system. This, in turn, reduced energy production, causing the hypothermia.

Evaluation of Clonidine suppression and various provocation tests in the diagnosis of pheochromocytoma

Recent investigations have shown that the widely used clonidine suppression test is sometimes fallible for the diagnosis of pheochromocytoma. A comparative assessment was made of the following suppression and provocation tests, the clonidine suppression test, and the glucagon, metoclopramide, and naloxone provocation tests. The assessment was performed in 6 patients with pheochromocytoma and in 19 patients without pheochromocytoma who were initially suspected of harboring a tumor. BP response did not predict the presence of pheochromocytoma in any test. Plasma norepinephrine (NE) concentrations determined at 120 and 180 min after oral 150 micrograms of clonidine gave false negative results in 2 of the 5 patients with pheochromocytoma tested. Both plasma NE and epinephrine (E) concentrations were measured before and sequentially after each provocative agent. Neither NE nor E responded to 1 mg of glucagon iv in 2 of the 4 patients with pheochromocytoma tested. Determination of the peak level, peak increment, and % peak increment of NE and E following 10 mg of naloxone iv did not distinguish the two groups. The % peak increments of both NE and E in all 4 patients with pheochromocytoma given 5 mg of metoclopramide iv exceeded the mean + 3 SD values of the patients without pheochromocytoma (25 + 28% for NE, and 25 + 42% for E). These results suggested that, when performed with judicious patient selection (ambiguous plasma or urinary catecholamine levels), the measurement of plasma catecholamines in response to metoclopramide can be a useful adjunctive tool in the diagnosis of pheochromocytoma.