Showing papers on "Epinephrine published in 2007"

Endogenous and Exogenous Cardiac Glycosides and their Mechanisms of Action

Abstract: Cardiac glycosides have been used for decades to treat congestive heart failure The recent identification of cardiotonic steroids such as ouabain, digoxin, marinobufagenin, and telocinobufagin in blood plasma, adrenal glands, and hypothalamus of mammals led to exciting new perspectives in the pathology of heart failure and arterial hypertension Biosynthesis of ouabain and digoxin occurs in adrenal glands and is under the control of angiotensin II, endothelin, and epinephrine released from cells of the midbrain upon stimulation of brain areas sensing cerebrospinal Na(+) concentration and, apparently, the body's K(+) content Rapid changes of endogenous ouabain upon physical exercise may favor the economy of the heart by a rise of intracellular Ca(2)(+) levels in cardiac and atrial muscle cells According to the sodium pump lag hypothesis, this may be accomplished by partial inhibition of the sodium pump and Ca(2+) influx via the Na(+)/Ca(2+) exchanger working in reverse mode or via activation of the Na(+)/K(+)-ATPase signalosome complex, generating intracellular calcium oscillations, reactive oxygen species, and gene activation via nuclear factor-kappaB or extracellular signal-regulated kinases 1 and 2 Elevated concentrations of endogenous ouabain and marinobufagenin in the subnanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells They may have a primary role in the development of cardiac dysfunction and failure because (i) offspring of hypertensive patients evidently inherit elevated plasma concentrations of endogenous ouabain; (ii) such elevated concentrations correlate positively with cardiac dysfunction, hypertrophy, and arterial hypertension; (iii) about 40% of Europeans with uncomplicated essential hypertension show increased concentrations of endogenous ouabain associated with reduced heart rate and cardiac hypertrophy; (iv) in patients with advanced arterial hypertension, circulating levels of endogenous ouabain correlate with BP and total peripheral resistance; (v) among patients with idiopathic dilated cardiomyopathy, high circulating levels of endogenous ouabain and marinobufagenin identify those individuals who are predisposed to progressing more rapidly to heart failure, suggesting that endogenous ouabain (and marinobufagenin) may contribute to toxicity upon digoxin therapy In contrast to endogenous ouabain, endogenous marinobufagenin may act as a natriuretic substance as well It shows a higher affinity for the ouabain-insensitive alpha(1) isoform of Na(+)/K(+)-ATPase of rat kidney tubular cells and its levels are increased in volume expansion and pre-eclampsia Digoxin, which is synthesized in adrenal glands, seems to counteract the hypertensinogenic action of ouabain in rats, as do antibodies against ouabain, for example, (Digibind) and rostafuroxin (PST 2238), a selective ouabain antagonist It lowers BP in ouabain- and adducin-dependent hypertension in rats and is a promising new class of antihypertensive medication in humans

Self-injectable Epinephrine for First-Aid Management of Anaphylaxis

Abstract: Anaphylaxis is a severe, potentially fatal systemic allergic reaction that is rapid in onset and may cause death. Epinephrine is the primary medical therapy, and it must be administered promptly. This clinical report focuses on practical issues concerning the administration of self-injectable epinephrine for first-aid treatment of anaphylaxis in the community. The recommended epinephrine dose for anaphylaxis in children, based primarily on anecdotal evidence, is 0.01 mg/kg, up to 0.30 mg. Intramuscular injection of epinephrine into the lateral thigh (vastus lateralis) is the preferred route for therapy in first-aid treatment. Epinephrine autoinjectors are currently available in only 2 fixed doses: 0.15 and 0.30 mg. On the basis of current, albeit limited, data, it seems reasonable to recommend autoinjectors with 0.15 mg of epinephrine for otherwise healthy young children who weigh 10 to 25 kg (22–55 lb) and autoinjectors with 0.30 mg of epinephrine for those who weigh approximately 25 kg (55 lb) or more; however, specific clinical circumstances must be considered in these decisions. This report also describes several quandaries in regard to management, including the selection of dose, indications for prescribing an autoinjector, and decisions regarding when to inject epinephrine. Effective care for individuals at risk of anaphylaxis requires a comprehensive management approach involving families, allergic children, schools, camps, and other youth organizations. Risk reduction entails confirmation of the trigger, discussion of avoidance of the relevant allergen, a written individualized emergency anaphylaxis action plan, and education of supervising adults with regard to recognition and treatment of anaphylaxis.

Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation.

Abstract: Objectives: Both epinephrine and vasopressin increase aortic and carotid arterial pressure when administered during cardiopulmonary resuscitation. However, we recently demonstrated that epinephrine reduces cerebral cortical microcirculatory blood flow. Accordingly, we compared the effects of nonadrenergic vasopressin with those of epinephrine on cerebral cortical microvascular flow together with cortical tissue Po 2 and Pco 2 as indicators of cortical tissue ischemia. Design: Randomized, prospective animal study. Setting: University-affiliated research laboratory. Subjects: Domestic pigs. Measurements and Main Results: The tracheae of ten domestic male pigs, weighing 40 ± 2 kg, were noninvasively intubated, and the animals were mechanically ventilated. A frontoparietal bilateral craniotomy was created. Microcirculatory blood flow was quantitated with orthogonal polarization spectral imaging. Blood flow velocity in pial and cortical penetrating vessels measuring <20 μm was graded from 0 (no flow) to 3 (normal). Cerebral cortical tissue carbon dioxide and oxygen tensions (P b co 2 and P b o 2 ) were measured concurrently using miniature optical sensors. Ventricular fibrillation, induced with an alternating current delivered to the right ventricular endocardium, was untreated for 3 mins. Animals were then randomized to receive central venous injections of equipressor doses of epinephrine (30 μg/kg) or vasopressin (0.4 units/kg) at 1 min after the start of cardiopulmonary resuscitation. After 4 mins of cardiopulmonary resuscitation, defibrillation was attempted. Spontaneous circulation was restored in each animal. However, postresuscitation microvascular flows and P b o 2 were greater and P b co 2 less after vasopressin when compared with epinephrine. We observed that a significantly greater number of cortical microvessels were perfused after vasopressin. Conclusions: Cortical microcirculatory blood flow was markedly reduced after epinephrine, resulting in a greater severity of brain ischemia after the restoration of spontaneous circulation in contrast to the more benign effects of vasopressin.

Food-induced anaphylaxis and repeated epinephrine treatments.

Abstract: Background Research on the use of more than 1 dose of epinephrine in the treatment of food-induced anaphylaxis is limited Objective To perform a medical record review to examine the frequency of repeated epinephrine treatments in patients presenting with food-induced anaphylaxis to the emergency department (ED) Methods We reviewed 39 medical records of patients who presented with food-induced allergic reactions to the Massachusetts General Hospital ED during a 1-year period The analysis focused on the timing of the onset of symptoms and on the number of epinephrine treatments given before and during the ED visit Results Of the 39 patients, 34 had an acute food-induced allergic reaction Nineteen had anaphylaxis Twelve patients with anaphylaxis (63%; 95% confidence interval, 38%-84%) received at least 1 dose of epinephrine, and 3 (16%; 95% confidence interval, 3%-40%) were given 2 doses Although statistical analysis was not possible, repeated epinephrine treatment occurred in patients with anaphylaxis to peanut or tree nut and hypotension There was no apparent association between time from ingestion of the causative agent to epinephrine treatment(s) Conclusions Of patients presenting to the ED with food-induced anaphylaxis, approximately 16% were treated with 2 doses of epinephrine This study supports the recommendation that patients at risk for food-induced anaphylaxis carry 2 doses of epinephrine Further study is needed to confirm these results and to expand them to patients who do not present to the ED because that group may have a lower frequency of epinephrine use

Alcohol‐induced stress in painful alcoholic neuropathy

Abstract: Chronic alcohol consumption induces a painful small-fiber peripheral neuropathy, the severity of which increases during alcohol withdrawal. Chronic alcohol consumption also produces a sustained increase in stress hormones, epinephrine and corticosterone, that is exacerbated during alcohol withdrawal. We report that adrenal medullectomy and administration of a glucocorticoid receptor antagonist, mifepristone (RU 38486), both prevented and reversed a model of painful peripheral neuropathy in alcohol binge-drinking rats. Chronic administration of stress levels of epinephrine to rats that had undergone adrenal medullectomy and were being fed the alcohol diet reconstituted this phenotype. Intrathecal administration of oligodeoxynucleotides antisense to the beta(2)-adrenergic- or glucocorticoid-receptor also prevented and reversed the pro-nociceptive effects of ethanol. Our results suggest a convergence of the effects of mediators of the hypothalamic-pituitary- and sympathoadrenal-stress axes on sensory neurons in the induction and maintenance of alcohol-induced painful peripheral neuropathy.

Sympathetic mechanisms of hypoglycemic counterregulation.

Abstract: In normal individuals hypoglycemic counterregulation is a multifactorial, redundant process that involves reduction of insulin secretion, increasing glucagon secretion, adrenergic activation, and increased growth hormone and cortisol secretion. Metabolically, these lead to increased glucose production, initially through glycogenolysis and later through gluconeogenesis, decreased muscle glucose oxidation and storage and increased release and use of alternative fuels, primarily free fatty acids. They also lead to hypoglycemic symptoms and hunger which increase food intake. These systems are designed to provide as much glucose as possible for brain glucose use. In patients with type 1 diabetes there are multiple impairments of these responses. Insulin does not decrease. Glucagon secretion is decreased or absent. Recovery from hypoglycemia is therefore dependent on the adrenergic response. Hypoglycemia increases plasma levels of both epinephrine and norepinephrine. These catechols are released primarily from the adrenal medulla. However, it is well documented that hypoglycemic increases muscle sympathetic nerve activity, and that both alpha and beta adrenergic activity increase. Increased beta-activity increases free fatty acid release which increase glucose production and decrease glucose utilization. The increased alpha-adrenergic activity's primary role is to counteract beta-adrenergic vasodilation. It may also reduce neurogenic and neuroglycopenic symptoms. Lastly, there is evidence that both cardiac and adrenergic sensitivity are altered in type 1 diabetes. It is hoped that this information can be used in the future to help develop ways to protect patients with type 1 diabetes from hypoglycemia and its adverse effects.

Epinephrine enhances lysosomal enzyme delivery across the blood brain barrier by up-regulation of the mannose 6-phosphate receptor.

Abstract: Delivering therapeutic levels of lysosomal enzymes across the blood–brain barrier (BBB) has been a pivotal issue in treating CNS storage diseases, including the mucopolysaccharidoses. An inherited deficiency of β-glucuronidase (GUS) causes mucopolysaccharidosis type VII that is characterized by increased systemic and CNS storage of glycosaminoglycans. We previously showed that the neonate uses the mannose 6-phosphate (M6P) receptor to transport phosphorylated GUS (P-GUS) across the BBB and that this transporter is lost with maturation. Induction of expression of this BBB transporter would make enzyme replacement therapy in the adult possible. Here, we tested pharmacological manipulation with epinephrine to restore functional transport of P-GUS across the adult BBB. Epinephrine (40 nmol) coinjected i.v. with 131I-P-GUS induced the transport across the BBB in 8-week-old mice. The brain influx rate of 131I-P-GUS (0.29 μl/g per min) returned to the level seen in neonates. Capillary depletion showed that 49% of the 131I-P-GUS in brain was in brain parenchyma. No increases of influx rate or the vascular space for 125I-albumin, a vascular marker, was observed with epinephrine (40 nmol), showing that enhanced passage was not caused by disruption of the BBB. Brain uptake of 131I-P-GUS was significantly inhibited by M6P in a dose-dependent manner, whereas epinephrine failed to increase brain uptake of nonphosphorylated GUS. Thus, the effect of epinephrine on the transport of 131I-P-GUS was ligand specific. These results indicate that epinephrine restores the M6P receptor-mediated functional transport of 131I-P-GUS across the BBB in adults to levels seen in the neonate.

Epinephrine Is Required for Normal Cardiovascular Responses to Stress in the Phenylethanolamine N-Methyltransferase Knockout Mouse

Abstract: Background— Epinephrine (EPI) is an important neurotransmitter and hormone. Its role in regulating cardiovascular function at rest and with stress is unclear, however. Methods and Results— An epinephrine-deficient mouse model was generated in which the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase was knocked out (KO). Blood pressure and heart rate were monitored by telemetry at rest and during graded treadmill exercise. Cardiac structure and function were evaluated by echocardiography in mice under 1 of 2 conditions: unstressed and lightly anesthetized or restrained and awake. In KO mice, resting cardiovascular function, including blood pressure, heart rate, and cardiac output, was the same as that in wild-type mice, and the basal norepinephrine plasma level was normal. However, inhibition of sympathetic innervation with the ganglion blocker hexamethonium caused a 54% smaller decrease in blood pressure in KO mice, and treadmill exercise caused an 11% higher increase in blood pres...

Stress-induced changes in epinephrine expression in the adrenal medulla in vivo.

Abstract: Immobilization (IMMO) stress was used to examine how stress alters the stress hormone epinephrine (EPI) in the adrenal medulla in vivo. In rats subjected to IMMO for 30 or 120 min, adrenal corticosterone increased to the same extent. In contrast, EPI changed very little, suggesting that EPI synthesis replenishes adrenal pools and sustains circulating levels for the heightened alertness and physiological responses of the 'flight or fight' response. In part, stress activates EPI via the phenylethanolamine N-methyltransferase (PNMT) gene as single or repeated IMMO elevated PNMT mRNA. The rise in PNMT mRNA was preceded by induction of the PNMT gene activator, Egr-1, with increases in Egr-1 mRNA, protein, and protein-DNA binding complex apparent. IMMO also evoked changes in Sp1 mRNA, protein, and Sp1-DNA complex formation, although for chronic IMMO changes were not entirely coincident. In contrast, glucocorticoid receptor and AP-2 mRNA, protein, and protein-DNA complex were unaltered. Finally, IMMO stress elevated PNMT protein. However, with seven daily IMMOs for 120 min and delayed killing, protein stimulation did not attain the highly elevated levels expected based on mRNA changes. The latter may perhaps suggest initiation of adrenergic desensitization to prolonged and repeated IMMO stress and/or dissociation of transcriptional and post-transcriptional regulatory mechanisms.

Heterozygous α2C-adrenoceptor-deficient mice develop heart failure after transverse aortic constriction

Abstract: Objective Feedback regulation of norepinephrine release from sympathetic nerves is essential to control blood pressure, heart rate and contractility. Recent experiments in gene-targeted mice have suggested that α2C-adrenoceptors may operate in a similar feedback mechanism to control the release of epinephrine from the adrenal medulla. As heterozygous polymorphisms in the human α2C-adrenoceptor gene have been associated with cardiovascular disease including hypertension and chronic heart failure, we have sought to characterize the relevance of α2C-gene copy number for feedback control of epinephrine release in gene-targeted mice. Methods Adrenal catecholamine release, basal hemodynamics and susceptibility to develop heart failure after transverse aortic constriction were tested in mice with two copies (+/+), one copy (+/−) or no functional α2C-adrenoceptor gene (α2C−/−). Results Heterozygous α2C-receptor deletion (α2C+/−) resulted in a 43% reduction of adrenal α2C mRNA copy number and in a similar decrease in α2-receptor-mediated inhibition of catecholamine release from isolated adrenal glands in vitro. Urinary excretion of epinephrine was increased by 74±15% in α2C+/− and by 142±23% in α2C−/− mice as compared with wild-type control mice. Telemetric determination of cardiovascular function revealed significant tachycardia but no hypertension in α2C-adrenoceptor-deficient mice. α2C+/− mice were more susceptible to develop cardiac hypertrophy, failure and mortality after left-ventricular pressure overload than α2C+/+ mice. Conclusion Adrenal α2-mediated feedback regulation of epinephrine secretion differs fundamentally from sympathetic feedback control. A single adrenoceptor subtype, α2C, operates without a significant receptor reserve to prevent elevation of circulating epinephrine levels. This genetic model may provide an experimental basis to study the pathophysiology of α2C-adrenoceptor dysfunction in humans.

Fight-or-Flight Response*

Abstract: Walter Cannon and his students and coworkers conducted an initial series of experiments from 1910 to 1911 that examined the link between emotional experiences and the secretion of epinephrine from the adrenal medulla. Employing an intestinal strip bioassay for the semiquantitative study of epinephrine secretion, he and his students determined that epinephrine secretion increased dramatically when a quiescent animal was exposed to a stressful or threatening stimulus. In addition, Cannon's laboratory used increases in glucose in the urine (glycosuria) as an indirect measure of epinephrine secretion with similar results. The connection between epinephrine secretion and increases in blood glucose led Cannon to write the following entry in his journal on January 20, 1911: “Got idea that adrenals in excitement serve to affect muscular power and mobilize sugar for muscular use – thus in wild state readiness for fight or run!” In time, “fight or run” was transformed into the more familiar fight or flight.

A Comparison of Epinephrine Only, Arginine Vasopressin Only, and Epinephrine Followed by Arginine Vasopressin on the Survival Rate in a Rat Model of Anaphylactic Shock

Abstract: Background: Epinephrine and more recently arginine vasopressin (AVP) alone or in combination have been proposed in patients with anaphylactic shock, but few experimental data exist. The authors investigated the effects of epinephrine only, AVP only, or epinephrine followed by AVP in a model of anaphylactic shock. Methods: Ovalbumin-sensitized Brown Norway rats were anesthetized, intubated, and shock induced with ovalbumin. Rats (n = 6/group) were randomly allocated to receive 5 min after shock onset: (1) saline (no-treatment group); (2) two boluses of epinephrine followed by continuous infusion (epinephrine group); (3) AVP bolus followed by continuous infusion (AVP group); (4) epinephrine bolus followed by AVP continuous infusion (epinephrine + AVP group). Mean arterial pressure (MAP) and skeletal muscle oxygen pressure (Ptio 2 ) were measured. Continuous infusion rates were titrated to reach MAP values of 60 mmHg. Survival was analyzed. Results: Without treatment, MAP and Ptio 2 decreased rapidly with 0% survival. In the epinephrine group, MAP and Ptio 2 recovered after an initial decrease, with 84% survival. In the AVP group, MAP was partially restored and subsequently decreased; Ptio 2 values decreased to values similar to those in the no-treatment group; survival was 0%. In the epinephrine + AVP group, MAP and Ptio 2 values increased more slowly as compared with the epinephrine group; survival was 100%. Conclusions: In this model of anaphylactic shock, early treatment with epinephrine followed by continuous epinephrine or vasopressin infusion resulted in an excellent survival rate, whereas vasopressin only resulted in a 100% death rate. These experimental results suggest that epinephrine must still be considered as the first-line drug to treat anaphylactic shock.

Impaired overnight counterregulatory hormone responses to spontaneous hypoglycemia in children with type 1 diabetes

Abstract: Abstract: To assess the changes in counterregulatory hormones overnight after an afternoon of structured exercise or sedentary activity in children with type 1 diabetes mellitus (T1DM), the Diabetes Research in Children Network (DirecNet) studied 50 children (10 to <18 yr) with T1DM in five clinical research centers on two separate days (with and without an afternoon exercise session) using a crossover design. Glucose, epinephrine, norepinephrine, cortisol, growth hormone (GH), and glucagon concentrations were measured hourly overnight. Nocturnal hypoglycemia [plasma glucose concentrations ≤70 mg/dL (3.9 mmol/L)] occurred more frequently on the nights following exercise (56 vs. 36%; p = 0.008). Mean hourly concentrations of most hormones did not differ between sedentary or exercise nights or between nights with or without hypoglycemia. Spontaneous nocturnal hypoglycemia only stimulated small increases in plasma epinephrine and GH concentrations and failed to cause a rise in norepinephrine, cortisol, or glucagon levels in comparison with values during the hour before or after hypoglycemia or other times during those same nights. Counterregulatory hormone responses to spontaneous nocturnal hypoglycemia were markedly decreased regardless of whether there was antecedent afternoon exercise in children with T1DM. Sleep‐induced impairments in counterregulatory hormone responses likely contribute to the increased risk of hypoglycemia during the entire overnight period in youth with T1DM.

Successful use of terlipressin in post-cardiac arrest resuscitation after an epinephrine-resistant anaphylactic shock to suxamethonium.

Abstract: EPINEPHRINE is considered in most guidelines as the first-line treatment of anaphylactic shock occurring during anesthesia. In some cases, epinephrine is not effective, and alternative therapies have been proposed, such as norepinephrine or metaraminol 1 or, more recently, arginine vasopressin. 2 ' 4 To our knowledge, we are the first to report the successful treatment of anaphylactic shock with terlipressin, a structural analog of arginine vasopressin.

Sympathoadrenal function in patients with paroxysmal hypertension : pseudopheochromocytoma. Commentary

Abstract: Objectives The causes of paroxysmal hypertension in patients in whom pheochromocytoma has been excluded ('pseudopheochromocytoma') usually remain unclear. Blood pressure disturbances and symptoms of catecholamine excess in these patients may reflect activation of the sympathetic nervous and adrenal medullary systems. We therefore examined sympathoadrenal function in patients with pseudopheochromocytoma compared with age-matched control subjects in whom there was no suspicion of pheochromocytoma. Methods Plasma catecholamines and hemodynamics were examined in response to intravenous glucagon, yohimbine, and trimethaphan in 11 patients with pseudopheochromocytoma and a comparison group of nine normotensive and five hypertensive volunteers. Adrenomedullary function was also assessed by abdominal 18 F-fluorodopamine positron emission tomography and measurements of plasma metanephrine, the O-methylated metabolite of epinephrine. Results Compared with controls, patients with pseudopheochromocytoma had normal plasma concentrations of norepinephrine, but 120% higher (P<0.05) baseline plasma concentrations of epinephrine, 80% higher (P<0.01) baseline plasma concentrations of metanephrine, and sixfold larger (P<0.05) increases in plasma epinephrine after glucagon. Adrenal 18 F-fluorodopamine-derived radioactivity did not differ between groups. Compared with changes in plasma norepinephrine, falls in blood pressure after trimethaphan were 13-fold larger (P<0.005) and increases in blood pressure after yohimbine were threefold larger (P<0.01) in pseudopheochromocytoma patients than in controls. Conclusion Patients with pseudopheochromocytoma exhibit a pattern of normal sympathetic noradrenergic outflow, adrenomedullary activation, and augmented blood pressure responses to changes in the sympathoneural release of norepinephrine.

Case report: Fentanyl-associated intraoperative anaphylaxis with pulmonary edema

Abstract: Purpose: To describe an atypical presentation of intraoperative anaphylaxis due to fentanyl. Clinical features: A 40-yr-old otherwise healthy woman was admitted for abdominal hysterectomy. She denied any drug allergies or past adverse anesthetic reactions. Physical examination, vital signs, and laboratory findings were all within normal limits. Twenty minutes after induction of general anesthesia with propofol, lidocaine, fentanyl, and rocuronium, she developed sudden onset of hypotension and bronchospasm. She was treated with fluids and epinephrine, but nonetheless required mechanical ventilation for 48 hr. Chest x-ray revealed pulmonary edema which resolved over two days. She recovered completely and was discharged home. Subsequent skin testing showed reactions to fentanyl and succinylcholine. Because the patient had not received succinylcholine, the cause of her anaphylaxis was attributed to fentanyl. The patient later returned for her hysterectomy and tolerated spinal anesthesia with bupivacaine and morphine. Conclusion: Anaphylaxis is a fulminant, unexpected, IgE-mediated allergic reaction which can be triggered by multiple agents. Common causative agents include neuromuscular blocking drugs, latex, antibiotics, colloids, hypnotics, and opioids. Fentanyl, however, is an extremely unusual cause of anaphylaxis. Pulmonary edema, although uncommon in anaphylaxis, can be a prominent feature, as was the case with this patient.

Beta-blockade in burns.

Abstract: A significant proportion of the mortality and morbidity of severe burns is attributable to the ensuing hypermetabolic response that typically lasts for at least 9-12 months post-injury. This is associated with impaired wound healing, increased infection risks, erosion of lean body mass, hampered rehabilitation and delayed reintegration of burn survivors into society. The endocrine status is markedly altered during this period with an initial and then sustained increase in proinflammatory 'stress' hormones such as cortisol and other glucocorticoids, and catecholamines including epinephrine and norepinephrine by the adrenal medulla and cortex. These hormones exert catabolic effects leading to muscle wasting, the intensity of which depends upon the percentage of total body surface area (TBSA) involved, as well as the time elapsed since initial injury. Pharmacological and non-pharmacological strategies may be used to reverse the catabolic effect of thermal injury. Of these, beta-adrenergic blockade with propranolol has been the most efficacious anti-catabolic therapy in the treatment of burns. The underlying mechanism of action of propranolol is still unclear, however its effect appears to occur due to an increased protein synthesis in the face of a persistent protein breakdown and reduced peripheral lipolysis. This article aims to review the current understanding of catecholamines in postburn muscle wasting and focuses on the clinical and metabolic effects of beta-blockade in severe burns.

Erythropoietin improves the postresuscitation myocardial dysfunction and survival in the asphyxia-induced cardiac arrest model.

Abstract: To investigate the effect of erythropoietin for the management of postresuscitation myocardial dysfunction following asphyxia-induced cardiac arrest. Male adult Wistar rats were used for the prospective controlled animal study. Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. Cardiopulmonary resuscitation with an intravenous injection of 0.01 mg/kg epinephrine and mechanical ventilation were started after 6.5 minutes of asphyxia. The resuscitated animals received either erythropoietin (5000 U/kg) or equivalent volume of 0.9% saline as placebo intravenously 3 minutes after return of spontaneous circulation. The erythropoietin treatment produced better left ventricular dP/dt40 and −dP/dt in the invasive hemodynamic measurements, and left ventricular fraction shortening by echocardiography. Administration of erythropoietin also improved three days survival among those successfully resuscitated. The molecular effects of erythropoietin were shown by activation of its down streaming Akt and ERK 42/44 signaling pathways. EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest.

Epinephrine dosing regimens comprising buccal, lingual or sublingual and injectable dosage forms

Abstract: The present invention relates to methods of administering a series of epinephrine doses for the treatment of allergic emergencies, including anaphylaxis, comprising buccal, lingual or sublingual epinephrine dosage forms and injectable epinephrine dosage forms. Also provided herein are kits and packaging systems useful in these methods.

Humor, as an adjunct therapy in cardiac rehabilitation, attenuates catecholamines and myocardial infarction recurrence.

Abstract: Background Catecholamines, especially epinephrine, are implicated in causing arrhythmias, hypertension, and recurrence of myocardial infarction (MI). Diminishing or blocking the effect of catecholamines is useful in cardiac rehabilitation. We have shown previously that a single 1-hour viewing of a humorous video attenuates epinephrine production. Design We hypothesized that daily participation in viewing humor would diminish catecholamine production and improve cardiac rehabilitation. Methods Forty-eight diabetic patients who had recently experienced an MI were divided into 2 matched groups and followed for 1 year in their cardiac rehabilitation programs. The experimental humor group was asked to view self-selected humor for 30 minutes daily as an adjunct to the standard cardiac therapy. Blood pressure, urinary and plasma epinephrine and norepinephrine levels, and 24-hour Holter recording were monitored monthly in both experimental humor and control groups. Results The patients in the humor group had fewer episodes of arrhythmias, lower blood pressure, lower urinary and plasma epinephrine and norepinephrine levels, less use of nitroglycerin for angina, and a markedly lower incidence of recurrent MI (2/24) than did the control group (10/24). Conclusion Humor appears to attenuate catecholamines and MI recurrence and thus may be an effective adjunct in post-MI care.

Epinephrine, but not vasopressin, improves survival rates in an adult rabbit model of asphyxia cardiac arrest.

Abstract: Although vasopressin has been reported to be more effective than epinephrine for cardiopulmonary resuscitation in ventricular fibrillation animal models, its efficacy in asphyxia model remains controversy. The purpose of this study was to investigate the effectiveness of vasopressin vs epinephrine on restoration of spontaneous circulation (ROSC) in a rabbit model of asphyxia cardiac arrest. Cardiac arrest was induced by clamping endotracheal tube. After 5 minutes of basic life-support cardiopulmonary resuscitation, animals who had no ROSC were randomly assigned to receive either epinephrine alone (epinephrine group; 200 μ g/kg) or vasopressin alone (vasopressin group; 0.8 U/kg). The coronary perfusion pressure (CPP) was calculated as the difference between the minimal diastolic aortic and simultaneously recorded right atrial pressure. Restoration of spontaneous circulation was defined as an unassisted pulse with a systolic arterial pressure of 60 mm Hg or higher for 5 minutes or longer. We induced arrest in 62 rabbits, 15 of whom had ROSC before drug administration and were excluded from analysis. The remaining 47 rabbits were randomized to epinephrine group (n = 24) and vasopressin group (n = 23). Before and after drug administration, CPP in epinephrine group increased significantly (from −4 ± 4 to 36 ± 9 mm Hg at peak value, P = .000), whereas CPP in vasopressin group increased only slightly (from 9 ± 5 to 18 ± 6 mm Hg at peak value, P = .20). After drug administration, 13 of 24 epinephrine rabbit had ROSC, and only 2 of 23 vasopressin rabbit had ROSC ( P Consequently, we conclude that epinephrine, but not vasopressin, increases survival rates in this adult rabbit asphyxia model.