Showing papers on "Epinephrine published in 1988"

Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs.

Abstract: Endothelin is a recently discovered vasoconstrictor peptide that is synthesized in certain vascular endothelial cells. We have identified the cardiovascular, renal, and hormonal responses that can be elicited in conscious dogs by intravenous administration of endothelin at rates of 10 and 30 ng.kg-1.min-1 for 60 min (0.24 and 0.72 nmol.kg-1/1-h infusion). Each dose of endothelin increased total peripheral resistance, arterial pressure, and left atrial pressure and decreased heart rate and cardiac output. Hematocrit increased by 4.8% (NS) and 22.9% (P less than 0.01) in response to the lower and higher infusion rates, respectively. Urinary sodium excretion, urine osmolality, and osmolar clearance decreased and free water clearance increased. The lower dose of endothelin decreased plasma norepinephrine and increased plasma atriopeptin. The higher dose increased plasma levels of vasopressin, renin, aldosterone, norepinephrine, epinephrine, and atriopeptin. The higher infusion rate of the peptide caused one or more brief vomiting episodes in four of five dogs. Although it is not yet known whether endothelin is a circulating hormone, it is clear that this peptide is capable of causing profound cardiovascular, renal, and endocrine alterations in conscious dogs. The possible relevance of these observations to physiological processes and to pathological conditions such as hypertension remains to be established.

Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs.

Abstract: Although large doses of epinephrine increase coronary perfusion pressure and flow during cardiopulmonary resuscitation, epinephrine also increases myocardial oxygen consumption during ventricular fibrillation. To test the hypothesis that epinephrine improves the balance between myocardial oxygen supply and demand during cardiopulmonary resuscitation, myocardial adenosine 5'-triphosphate (ATP) and lactate concentrations were measured before and immediately after 10 minutes of cardiopulmonary resuscitation in 10 control dogs and 10 dogs given intravenous epinephrine (1-mg bolus followed by 0.2 mg/min). Left ventricular myocardial blood flow during cardiopulmonary resuscitation was measured with radioactive microspheres and was significantly higher in the epinephrine group (48 +/- 11 vs. 21 +/- 4 ml/min/100 g, p less than 0.05). However, myocardial lactate concentration increased significantly (p less than 0.01) after cardiopulmonary resuscitation in both groups and tended to increase more in epinephrine-treated animals. Myocardial ATP concentration decreased significantly (p less than 0.05) and by comparable amounts in the two groups. These findings suggest that large doses of epinephrine may fail to improve the balance between myocardial oxygen supply and demand during cardiopulmonary resuscitation, even when they result in a substantial increase in coronary blood flow.

Catecholamine toxicity in cerebral cortex in dissociated cell culture.

Abstract: Identification of endogenous toxins and characterization of the mechanisms by which toxins produce cell injury and death may help understand both normal modeling of cell populations and connections in the CNS as well as abnormal cell loss The toxicity of catecholamines intrinsic to the CNS was investigated using the model system of rat cerebral cortex in dissociated cell culture All catecholamines tested, including norepinephrine (NE), dopamine, and epinephrine, were toxic to neurons as well as glia at a concentration of 25 microM when added to cultures 24 hr after plating Toxicity was evident after 48 hr exposure to NE, as monitored by loss of cells from the cultures Toxicity did not seem to be mediated by adrenergic receptors because, although the beta-adrenergic agonist isoproterenol (but not the alpha-adrenergic agonist phenylephrine) was similar in its toxic effect to NE, the beta- adrenergic antagonist atenolol did not block the toxic effect of NE Toxicity could be mimicked by hydrogen peroxide, a product of the oxidative degradation of catecholamines Toxicity of NE was blocked by catalase The neurotoxin 6-hydroxydopamine (6-OHDA), supposedly selective for catecholaminergic neurons, was found to be toxic over the same concentration range as NE These results suggest that endogenous catecholamines may play a role in normal and abnormal cell death, and suggest that caution be used in relying on the specificity of 6-OHDA and other supposedly selective neurotoxins

Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs.

Abstract: Although large doses of epinephrine increase coronary perfusion pressure and flow during cardiopulmonary resuscitation, epinephrine also increases myocardial oxygen consumption during ventricular fibrillation. To test the hypothesis that epinephrine improves the balance between myocardial oxygen supply and demand during cardiopulmonary resuscitation, myocardial adenosine 5'-triphosphate (ATP) and lactate concentrations were measured before and immediately after 10 minutes of cardiopulmonary resuscitation in 10 control dogs and 10 dogs given intravenous epinephrine (1-mg bolus followed by 0.2 mg/min). Left ventricular myocardial blood flow during cardiopulmonary resuscitation was measured with radioactive microspheres and was significantly higher in the epinephrine group (48 +/- 11 vs. 21 +/- 4 ml/min/100 g, p less than 0.05). However, myocardial lactate concentration increased significantly (p less than 0.01) after cardiopulmonary resuscitation in both groups and tended to increase more in epinephrine-tre...

Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats

Abstract: Capsaicin enhances adrenal medullary catecholamine secretion. The participation of the central nervous system on this enhancement by capsaicin was investigated in alpha-chloralose-urethan- or halothane-anesthetized rats. Intravenous administration of capsaicin caused a rapid and marked increase in adrenal sympathetic nerve activity. The nerve activity began to show an increase with the administration of capsaicin at a dosage of 20 micrograms/kg and significantly increased with a dosage of 200 micrograms/kg, i.e., capsaicin was found to cause a dose-dependent increase in adrenal nerve activity. Cholinergic blocking with hexamethonium bromide and atropine sulfate (1 and 5 mg/kg iv, respectively) attenuated the adrenal epinephrine secretion caused by capsaicin. The direct action of capsaicin on adrenal catecholamine secretion was examined using a retrograde perfusion system of left adrenal gland. Up to 8.2 X 10(-5) M capsaicin did not enhance catecholamine secretion from the adrenal gland. These results suggest that the enhancement of physiological catecholamine secretion by capsaicin is mainly through activation of the central nervous system.

Epinephrine potentiates human platelet activation but is not an aggregating agent

Abstract: Epinephrine can in certain in vitro conditions induce the aggregation of human platelets and could play an important role in vivo in the appearance of thrombotic disorders when catecholamine levels are increased. This study examines some functional and biochemical responses to epinephrine. Epinephrine induces the aggregation and serotonin secretion of human platelets in citrated plasma. This is not due to a direct effect of citrate itself, such as the lowering of plasma free Ca2+ but more likely to the generation of traces of thrombin during blood collection, as suggested by abrogation of these platelet responses when hirudin was added before citrate. When washed human platelets suspended in Tyrode buffer containing 2 mM Ca2+, 0.35% albumin and apyrase, and 0.1-100 microM epinephrine were used, no shape change, aggregation, or secretion of serotonin was observed, nor was the platelet ultrastructure modified. Epinephrine does not modify platelet membrane fluidity, as studied with the lipophilic fluorescent probe trimethylammonium-diphenylhexatriene. It has no direct effect on fibrinogen binding to intact platelets, intracellular Ca2+ levels measured by quin2, or protein phosphorylation. Epinephrine potentiates the action of all types of aggregating agents on aggregation, secretion, intracellular Ca2+ levels, membrane fluidity, fibrinogen binding, or protein phosphorylation. These effects are mediated by alpha 2-adrenergic agonists and inhibited by alpha 2-adrenergic antagonists. This study shows that epinephrine alone does not induce modifications of morphology, metabolism, or function of intact and functional washed human platelets and that it cannot be considered per se as an aggregating agent. However, epinephrine interacts with alpha 2-adrenergic receptors on human platelets and potentiates biochemical and aggregatory responses induced by other platelet agonists.

Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat.

Abstract: Pyridoxal phosphate is the coenzyme of various decarboxylases involved in the formation of monoamine neurotransmitters such as gamma-aminobutyric acid, serotonin, dopamine, and norepinephrine. Adult male Sprague-Dawley rats placed on a pyridoxine-deficient diet for 8 weeks showed significant hypertension compared with pyridoxine-supplemented controls. Hypothalamic contents of pyridoxal phosphate, gamma-aminobutyric acid, and serotonin in the pyridoxine-deficient rats were significantly lower than those in pyridoxine-supplemented controls. Hypertension was associated with sympathetic stimulation. Treatment of pyridoxine-deficient rats with a single dose of pyridoxine (10 mg/kg body weight) reversed the blood pressure to normal levels within 24 hours, with concomitant restorations of hypothalamic serotonin and gamma-aminobutyric acid as well as the return of plasma norepinephrine and epinephrine to normal levels. Also, pyridoxine treatment reversed the hypothalamic hypothyroidism observed in pyridoxine-deficient rats. These results indicate an association between pyridoxine deficiency and sympathetic stimulation leading to hypertension.

Glucose homeostasis and insulin secretion during isoflurane anesthesia in humans.

Abstract: The effect of isoflurane-air anesthesia on glucose tolerance in humans was investigated using two successive intravenous glucose tolerance tests (IVGTT). After a first IVGTT while awake, patients received a second IVGTT either while awake (group I), during anesthesia with isoflurane-air and pancuronium without surgical stimulation (group II), or during the same anesthetic technique but combined with surgery (group III). Isoflurane seemed to induce glucose intolerance (glucose disappearance rate K10-60 min = 1.628 +/- 0.462% min-1 [control] versus 1.086 +/- 0.920% min-1 [anesthesia], P less than 0.05) partly due to a decreased glucose induced insulin response. Growth hormone and norepinephrine levels were also increased during anesthesia. Epinephrine levels were lowered by isoflurane anesthesia. Although glucose intolerance was marked during surgery (K10-60 min = 0.892 +/- 0.286% min-1), the glucose-induced insulin response remained similar to that observed in patients in group II, while growth hormone, cortisol, epinephrine, and norepinephrine concentrations increased significantly. These known stress factors thus seemed to enhance glucose intolerance through a diminished response to insulin action and/or an enhanced hepatic glucose output, rather than by further impairing pancreatic insulin secretion.

Memory enhancement with posttraining intraventricular glucose injections in rats.

Abstract: Recent findings suggest that peripheral epinephrine enhancement of memory storage may be mediated in part by an increase in circulating glucose levels subsequent to epinephrine release or injection. Because glucose, unlike epinephrine, has ready access to the central nervous system, it is possible that glucose acts directly on central processes to enhance memory. To test this possibility, rats were trained on a one-trial inhibitory avoidance task and received immediate or delayed injections of glucose in artificial cerebrospinal fluid. On retention tests 24 hr after training, animals that received 3 or 5 micrograms glucose (in 1 microl cerebrospinal fluid over 3 min) had significantly enhanced performance of the learned response. These findings are consistent with the view that glucose can regulate the storage of new information by acting on central processes. Whether there are additional peripheral contributions to glucose effects on memory remains to be determined.

Stress and Autonomic Nervous System in Type II Diabetes: A Hypothesis

Abstract: Many investigators have begun to speculate that the sympathetic nervous system is involved in the pathophysiology of type II (noninsulin-dependent) diabetes mellitus (1–4). Recalling the early observations of Claude Bernard, who found that hyperglycemia could be produced in normal rabbits by lesioning the area of the hypothalamus, several groups have noted that hyperglycemia can be produced by chemical stimulation of the brain with morphine as well as with a variety of endogenous neuropeptides and can be abolished by bilateral adrenalectomy (1,5). Similarly, hyperglycemia has been shown to result from slow intravenous infusion of epinephrine (6) as well as from certain forms of stress that produce prolonged sympathetic discharge (7).

A randomized double-blind, placebo-controlled trial of dexamethasone and racemic epinephrine in the treatment of croup.

Abstract: Seventy-two children hospitalized for croup received on admission a single dose of either 06 mg/kg dexamethasone or an equivalent placebo intramuscularly from randomized ampules; subsequently the same patients were randomized to receive either nebulized racemic epinephrine or saline by intermittent positive pressure breathing Of the four treatment groups those receiving a placebo injection and nebulized saline had the slowest recovery by all criteria Dexamethasone and nebulized epinephrine reduced the symptoms and hastened recovery, but dexamethasone was more effective by clinical evaluation at 6 and 12 hours post admission The patients given dexamethasone had a significantly shorter hospital stay than those receiving placebo We conclude that a single injection of a potent corticosteroid is beneficial in acute spasmodic croup Nebulized racemic epinephrine given with an appropriate device is also effective, but the effect of epinephrine is less remarkable in patients treated with dexamethasone

Platelet aggregation in hypertension and the effects of antihypertensive treatment.

Abstract: The major findings of a review of the literature on platelet aggregation in hypertensive human subjects and the effects of antihypertensive agents were as follows: (1) There is an increased platelet aggregatory response to epinephrine and ADP in hypertensives with MAP greater than 120 mmHg. (2) Treatment with propranolol decreases the aggregatory response to ADP, but it may enhance the response to epinephrine. (3) Treatment with calcium blockers in normotensives decreases the aggregatory response to epinephrine. Further work needs to be done to answer the questions raised by this review. Since the major goal, yet unachieved, of antihypertensive therapy is reduction of the incidence of CHD, the anti-thrombotic or thrombotic potential of antihypertensive agents must be known. Future clinical trials of drug therapy for hypertension should be designed to include at least a determination of platelet aggregation in response to both ADP and epinephrine.

Successful Resuscitation From Cardiac Arrest Using High-Dose Epinephrine Therapy: Report of Two Cases

Abstract: A patient with cardiac arrest failed to respond to prolonged standard therapy for multiple dysrhythmias. High-dose intravenous epinephrine hydrochloride was administered 22 and 26 minutes after arrest. Coarsening of ventricular fibrillation and defibrillation with subsequent return of spontaneous circulation occurred. The patient was neurologically intact when eventually discharged. In another patient, prolonged asystole failed to respond to standard advanced cardiac life-support therapy. High-dose epinephrine was given 38 minutes after arrest, and return of spontaneous circulation subsequently occurred. Intensive treatment efforts were discontinued after admission to the hospital, and the patient died. The temporal sequence in these patients suggests that high-dose epinephrine therapy caused the return of spontaneous circulation. Recent studies suggest that presently recommended epinephrine doses may be too low, and investigation of graded epinephrine doses for the treatment of cardiac arrest is indicated. (JAMA1988;259:3031-3034)

Plasma catecholamines and resuscitation from prolonged cardiac arrest.

Abstract: Plasma catecholamine levels rise markedly with cardiac arrest and attempted resuscitation. W e examined whether epinephrine (EPI) or norepinephrine (NE) plasma concentrations could predict resuscitation outcome. In nine mongrel dogs. EPI and NE levels were drawn before cardiac arrest and after 8 and

Epinephrine facilitates neurogenic vasoconstriction in humans.

Abstract: Numerous studies have suggested that epinephrine may facilitate neural release of NE. There have been no studies in humans that demonstrate the functional significance of this action. To determine whether epinephrine facilitates neurogenic vasoconstriction in humans, we contrasted forearm vasoconstrictor responses to a reflex stimulus (lower body negative pressure [LBNP]) and to intraarterial NE before, during, and 30 min after infusion of epinephrine (50 ng/min) or isoproterenol (10 or 25 ng/min) into a brachial artery. These doses had no systemic effects. We reasoned that if prejunctional stimulation of beta receptors by epinephrine and isoproterenol had functional significance, the vasoconstrictor response to LBNP would be potentiated in comparison to the response to NE (postjunctional mechanism). Studies were done on 23 normal male volunteers. Forearm blood flow was measured with a strain gauge plethysmograph and intraarterial pressure was recorded. The ratio of vasoconstrictor responses to LBNP/NE was used as an index of neural release of the neurotransmitter NE. This ratio increased during infusions of both epinephrine and isoproterenol. 30 min after epinephrine the vasoconstrictor response to LBNP (n = 15) was augmented from +9.9 +/- 2.2 (SE) resistance units (RU) before epinephrine to +16.4 +/- 3.2 RU (P less than 0.05); whereas the response to NE (n = 8) tended to decrease from +8.8 +/- 3.1 RU before to +4.2 +/- 1.2 RU after epinephrine (P greater than 0.05). In contrast, 30 min after isoproterenol the vasoconstrictor responses to LBNP and NE were the same as before isoproterenol. The augmented ratio of responses to LBNP/NE after epinephrine and not after isoproterenol supports the concept that epinephrine, but not isoproterenol, is taken up by the adrenergic terminal, is released subsequently during reflex stimulation, and augments the release of the neurotransmitter NE. These experiments provide the first hemodynamic evidence in humans that epinephrine and isoproterenol facilitate neurogenic vasoconstriction. The sustained effect of epinephrine in contrast to isoproterenol suggests that the late facilitation by epinephrine is related to its neural uptake and subsequent release.

Pancreatic noradrenergic nerves are activated by neuroglucopenia but not by hypotension or hypoxia in the dog. Evidence for stress-specific and regionally selective activation of the sympathetic nervous system.

Abstract: To determine if acute stress activates pancreatic noradrenergic nerves, pancreatic norepinephrine (NE) output (spillover) was measured in halothane-anesthetized dogs. Central neuroglucopenia, induced by intravenous 2-deoxy-D-glucose [( 2-DG] 600 mg/kg + 13.5 mg/kg-1 per min-1) increased pancreatic NE output from a baseline of 380 +/- 100 to 1,490 +/- 340 pg/min (delta = +1,110 +/- 290 pg/min, P less than 0.01). Surgical denervation of the pancreas reduced this response by 90% (delta = +120 +/- 50 pg/min, P less than 0.01 vs. intact innervation), suggesting that 2-DG activated pancreatic nerves by increasing the central sympathetic outflow to the pancreas rather than by acting directly on nerves within the pancreas itself. These experiments provide the first direct evidence of stress-induced activation of pancreatic noradrenergic nerves in vivo. In contrast, neither hemorrhagic hypotension (50 mmHg) nor hypoxia (6-8% O2) increased pancreatic NE output (delta = +80 +/- 110 and -20 +/- 60 pg/min, respectively, P less than 0.01 vs. neuroglucopenia) despite both producing increases of arterial plasma NE and epinephrine similar to glucopenia. The activation of pancreatic noradrenergic nerves is thus stress specific. Furthermore, because both glucopenia and hypotension increased arterial NE, yet only glucopenia activated pancreatic nerves, it is suggested that a regionally selective pattern of sympathetic activation can be elicited by acute stress, a condition in which sympathetic activation has traditionally been thought to be generalized and nondiscrete.

Differential response of substance P-containing subtypes of adrenomedullary cells to different stressors.

Abstract: Adrenal medullary cells produce not only the catecholamines norepinephrine and epinephrine but also a number of peptides; hence, they can be subclassified according to their peptide quality. The present study was an attempt to test whether different stressors address different subclasses of adrenal medullary cells. The adrenal gland of intact male rats was implanted with a dialysis system, and the jugular vein was catheterized. One day after surgery, the adrenal dialysis system was connected to a perfusion pump, and Ringer solution was used for dialysis; dialysate fractions were collected at 15-min intervals, and blood was withdrawn at the end of each fraction period after a 2-h equilibration period. The basal release rates of pituitary PRL and adrenal corticosterone, measured in plasma, and of epinephrine, norepinephrine, and substance P (SP) measured in the adrenal dialysates, were constant during the preshock period. SP concentrations in the blood were below the detection limit of the RIA. Application ...

Effect of physical training on the capacity to secrete epinephrine

Abstract: Epinephrine responses to hypoglycemia and to identical relative work loads have been shown to be higher in endurance-trained athletes than in untrained subjects. To test the hypothesis that training increases the adrenal medullary secretory capacity, we studied the effects of glucagon (1 mg/70 kg iv), acute hypercapnia (inspired O2 fraction = 7%), and acute hypobaric hypoxia (inspired Po2 = 87 Torr), respectively, on the epinephrine concentration in arterialized hand vein blood in eight endurance-trained athletes [T, O2 uptake = 66 (62-70) ml.min-1.kg-1] and seven sedentary males [C, O2 uptake = 46 (41-50)]. In response to identical increments in glucagon concentrations, plasma epinephrine increased more in T than in C subjects [0.87 +/- 0.11 vs. 0.38 +/- 0.14 (SE) nmol/l, P less than 0.05]. In response to hypercapnia [arterial PCO2 = 56 +/- 0.7 Torr (T) and 55 +/- 0.4 (C), P greater than 0.05], the increment in epinephrine was significant in T (0.38 +/- 0.11 nmol/l) but not (P less than 0.1) in C subjects (0.22 +/- 0.11). Hypoxia [arterial PO2 = 42 +/- 2 Torr (T) and 41 +/- 2 (C), P greater than 0.05] increased epinephrine in T (0.22 +/- 0.10 nmol/l, P less than 0.05) but not in C subjects (0.01 +/- 0.07). The plasma norepinephrine concentration never changed, whereas heart rate always increased, the increase being higher (P less than 0.05) in T than in C subjects only during hypercapnia. The results indicate that training increases the capacity to secrete epinephrine.

Secretion of corticotrophin releasing factor from the adrenal during splanchnic nerve stimulation in conscious calves.

Abstract: 1. The output of corticotrophin releasing factor-like immunoreactivity (CRF) from the adrenal gland has been investigated using the 'adrenal clamp' technique in conscious calves. 2. Stimulation of the peripheral end of the splanchnic nerve for 10 min increased the mean output of CRF progressively, so that it had risen by about twentyfold, to a peak incremental value of 24 +/- 4 pmol min-1 kg-1 at 10 min. This response was significantly increased by stimulating in bursts at 40 Hz for 1 s at 10 s intervals, which raised the mean CRF output by 44 +/- 7 pmol min-1 kg-1 at 10 min (P less than 0.05). 3. The mean output of adrenaline and noradrenaline rose more abruptly in response to splanchnic nerve stimulation with peak incremental values realized within 2.5 min. However, the ratios of adrenal CRF to catecholamine output were closely similar during the later stages of stimulation (7.5-10 min). There was a similarly abrupt rise in adrenal cortisol output in response to splanchnic nerve stimulation which was, nevertheless, linearly related to arterial plasma ACTH concentration throughout. 4. In hypophysectomized calves, administration of adrenocorticotrophic hormone (ACTH1-24) at a dose of 5 ng min-1 kg-1 reduced the output of adrenal CRF in response to splanchnic nerve stimulation by about 50% (P less than 0.05). 5. CRF isolated from adrenal venous effluent plasma, collected both at rest and during splanchnic nerve stimulation, was separated by reverse-phase high-pressure liquid chromatography and found to elute in a position identical to that of human 41CRF. This suggests that adrenal CRF is structurally closely similar to its pituitary counterpart.

Influence of androgenic status on the α2/β-adrenergic control of lipolysis in white fat cells: predominant α2-antilipolytic response in testosterone-treated-castrated hamsters

Abstract: The aim of this study was to evaluate the influence of castration with or without testosterone propionate (TP) administration (one daily injection of 1 mg for 10 days) on the fat cell lipolytic activity in male hamsters. Basal and maximal lipolytic responses to the pure β-adrenergic agonist isoproterenol, the mixed α2- and β-adrenergic agonist epinephrine, and the nonadrenergic compounds ACTH and 3- isobutyl-1-methylxanthine were all reduced by half in castrated animals. TP treatment restored these defective responses to control values, except the response to epinephrine which remained paradoxically unchanged. Sensitivity of lipolysis to epinephrine was unimpaired by castration but markedly reduced (10-fold) in TP-treated castrated hamsters. The antilipolytic potencies of the α2-component of epinephrine and of the two α2- agonists, UK 14304 and clonidine, were reduced by half in castrated animals, and returned to a value slightly higher than control after TP treatment. These changes in lipolysis were acco...