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At least 19 recordsLinked to original sources
PubMed2000

Nebulized racemic epinephrine for extubation of newborn infants.

BACKGROUND: Following a period of mechanical ventilation, post-extubation upper airway obstruction can occur in newborn infants, especially after prolonged, traumatic or multiple intubations. The subsequent increase in upper airway resistance may lead to respiratory insufficiency and failure of extubation. The vasoconstrictive properties of epinephrine, and its proven efficacy in the treatment of croup in infants, has led to the routine use of inhaled nebulised epinephrine immediately post-extubation in some neonatal units. It is also recommended for neonates with post-extubation tracheal obstruction and stridor in neonatal and respiratory textbooks and reviews. OBJECTIVES: The primary objective was to assess whether nebulised epinephrine administered immediately after extubation in neonates weaned from IPPV decreases the need for subsequent additional respiratory support. SEARCH STRATEGY: Searches were made of Medline (MeSH search terms 'epinephrine' and 'exp infant, newborn'), the Oxford Database of Perinatal trials, expert informants and journal hand searching mainly in the English language, expert informant searches in the Japanese language by Prof. Ogawa, previous reviews including cross references, abstracts, and conference and symposia proceedings. SELECTION CRITERIA: All randomised and quasi-randomised control trials in which nebulised epinephrine was compared with placebo immediately post-extubation in newborn infants who have been weaned from IPPV and extubated, with regard to clinically important outcomes (i.e. need for additional respiratory support, increase in oxygen requirement, respiratory distress, stridor or the occurrence of side effects). DATA COLLECTION AND ANALYSIS: No studies met our criteria for inclusion in this review. MAIN RESULTS: No studies were identified which looked at the effect of inhaled nebulised epinephrine on clinically important outcomes in infants being extubated. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: There is no evidence either supporting or refuting the use of inhaled nebulised racemic epinephrine in newborn infants. IMPLICATIONS FOR RESEARCH: randomised controlled trials are needed comparing inhaled nebulised racemic epinephrine with placebo in neonates post-extubation. This should be looked at both as a routine treatment post-extubation and as specific treatment for post-extubation upper airway obstruction. Study populations should include the group of infants at highest risk for upper airway obstruction from mucosal swelling because of their small glottic and sub-glottic diameters (ie those infants with birthweights less than 1000 grams).

Administration, Inhalation↗
PubMed2002

Epinephrine markedly improves thoracic epidural analgesia produced by a small-dose infusion of ropivacaine, fentanyl, and epinephrine after major thoracic or abdominal surgery: a randomized, double-blinded crossover study with and without epinephrine.

UNLABELLED: We have shown that epinephrine markedly improves the analgesic effect of a thoracic epidural infusion of bupivacaine and fentanyl. Ropivacaine has an intrinsic vasoconstrictive effect, and epinephrine may therefore not have the same pharmacokinetic interaction in a ropivacaine-fentanyl infusion; but a possible spinal cord alpha(2)-agonist effect of epinephrine would give the same positive pharmacodynamic interaction with ropivacaine and fentanyl during epidural analgesia. In a prospective, randomized, crossover study, a thoracic epidural infusion of ropivacaine 1 mg/mL and fentanyl 2 microg/mL with or without epinephrine 2 microg/mL was given to 12 patients in a double-blinded manner after major thoracic or upper abdominal surgery. Main outcome measures were pain intensity at rest and when coughing, evaluated on a visual analog scale. Extent of sensory blockade was evaluated by determining dermatomal hypoesthesia to cold. Pain increased (P < 0.001) and hypoesthetic dermatomal segments decreased (P < 0.001) when epinephrine was omitted from the triple epidural infusion. After 3 h without epinephrine, pain intensity when coughing was unacceptable despite rescue analgesia. After restarting the triple epidural mixture with epinephrine, pain was again reduced to mild pain when coughing, and the sensory blockade was restored. The mixture with epinephrine caused less nausea and facilitated mobilization. We conclude that epinephrine improves the pain relief and reduces the side effects of a thoracic epidural infusion of ropivacaine and fentanyl after major thoracic or upper abdominal surgery. IMPLICATIONS: Epidural epinephrine markedly improves the pain relief and sensory blockade of a small-dose thoracic epidural infusion of ropivacaine and fentanyl. Nausea was reduced, and mobilization of the patients was facilitated.

Adjuvants, Anesthesia↗
PubMed1991

[Effect of lidocaine-epinephrine-dextran solution on the plasma epinephrine concentration during spinal surgery--how to avoid circulatory complications due to the use of epinephrine for hemostasis].

Epinephrine infiltrated for hemostasis may cause adverse effect on the circulatory system and the effect can be potentiated by surgical stimulation. Local infiltration of lidocaine-epinephrine-dextran solution (LED) at the surgical site is advantageous for this purpose since nerve blocking action of lidocaine attenuates surgical stimulation and dextran suppresses the transfer of injected epinephrine to the blood stream, thereby reducing the adverse effect of epinephrine. LED, however, could be injected accidentally into vessels. This is one of the important causes of raising the plasma epinephrine concentration to a dangerous level. The author believes that the following maneuvers are helpful to avoid the rise of plasma epinephrine concentration to a dangerous level; 1) injecting not more than 0.05 ml.kg-1 at a time, 2) monitoring the arterial pressure waves and ECG during the injection by use of a continuous recording device, and 3) halting the injection immediately whenever sudden changes in the arterial pressure and in the height of the T wave in ECG were observed. More importantly, surgeon's cooperation is essential for anesthesiologists to execute these maneuvers.

Adult↗
PubMed1992

Use of cardiopulmonary bypass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from post-countershock electromechanical dissociation.

STUDY OBJECTIVE: To determine the effects of cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, and standard-dose epinephrine on perfusion pressures, myocardial blood flow, and resuscitation from post-countershock electromechanical dissociation. DESIGN: Prospective, controlled laboratory investigation using a canine cardiac arrest model randomized to receive one of three resuscitation therapies. INTERVENTIONS: After the production of post-countershock electromechanical dissociation, 25 animals received ten minutes of basic CPR and were randomized to receive cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, or standard-dose epinephrine. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow was measured using a colored microsphere technique at baseline, during basic CPR, and after intervention. Immediate and two-hour resuscitation rates were determined for each group. Return of spontaneous circulation was achieved in eight of eight cardiopulmonary bypass with standard-dose epinephrine compared with four of eight high-dose epinephrine and three of eight standard-dose epinephrine animals (P less than .04). One animal was resuscitated with CPR alone and was excluded. Survival to two hours was achieved in five of eight cardiopulmonary bypass with standard-dose epinephrine, four of eight high-dose epinephrine, and three of eight standard-dose epinephrine animals (NS). Coronary perfusion pressure increased significantly in the cardiopulmonary bypass with standard-dose epinephrine group when compared with the other groups (cardiopulmonary bypass with standard-dose epinephrine, 76 +/- 45 mm Hg; high-dose epinephrine, 24 +/- 12 mm Hg; standard-dose epinephrine, 3 +/- 14 mm Hg; P less than .005). Myocardial blood flow was higher in cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine animals compared with standard-dose epinephrine animals but did not reach statistical significance. Cardiac output increased during cardiopulmonary bypass with standard-dose epinephrine (P = .001) and standard-dose epinephrine (NS) compared with basic CPR but decreased after epinephrine administration in the high-dose epinephrine group (NS). CONCLUSION: Resuscitation from electromechanical dissociation was improved with cardiopulmonary bypass and epinephrine compared with high-dose epinephrine or standard-dose epinephrine alone. However, there was no difference in survival between groups. Cardiopulmonary bypass with standard-dose epinephrine resulted in higher cardiac output, coronary perfusion pressure, and a trend toward higher myocardial blood flow. A short period of cardiopulmonary bypass with epinephrine after prolonged post-countershock electromechanical dissociation cardiac arrest can re-establish sufficient circulation to effect successful early resuscitation.

Animals↗
PubMed2000

Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis?

BACKGROUND: For out-of-hospital treatment of anaphylaxis, inhalation of epinephrine from a pressurized metered-dose inhaler is sometimes recommended as a noninvasive, user-friendly alternative to an epinephrine injection. OBJECTIVE: To determine the feasibility of administering an adequate epinephrine dose from a metered-dose inhaler in children at risk for anaphylaxis by assessing the rate and extent of epinephrine absorption after inhalation. METHODS: We performed a prospective, randomized, observer-blind, placebo-controlled, parallel-group study in 19 asymptomatic children with a history of anaphylaxis. Based on the child's weight, 10, 15, or 20 carefully supervised epinephrine or placebo inhalations were attempted. Before dosing, and at intervals from 5 to 180 minutes after dosing, we monitored plasma epinephrine concentrations, blood glucose, heart rate, blood pressure, and adverse effects. RESULTS: Eleven children (mean +/- standard error of the mean: 9 +/- 1 years and 33 +/- 3 kg) in the epinephrine group were able to inhale 11 +/- 2 (range: 3-20) puffs, equivalent to 74% +/- 7% of the precalculated dose or 0.078 +/- 0.009 mg/kg. They achieved a mean peak plasma epinephrine concentration of 1822 +/- 413 (range: 230-4518) pg/mL at 32.7 +/- 6.2 minutes. Eight children (10 +/- 1 years of age and 33 +/- 5 kg) in the placebo group were able to inhale 12 +/- 2 (range: 8-20) puffs, 89% +/- 3% of the precalculated dose, and had a peak endogenous plasma epinephrine concentration of 1316 +/- 247 (range: 522-2687) pg/mL at 44.4 +/- 16.7 minutes. In the children receiving epinephrine compared with those receiving placebo, mean plasma epinephrine concentrations were not significantly higher at any time, mean blood glucose concentrations were significantly higher from 10 to 30 minutes, mean heart rate was not significantly different at any time, and mean systolic and diastolic blood pressures were not significantly increased at most times. After the inhalations of epinephrine or placebo, the children complained of bad taste and many experienced cough or dizziness. After inhaling epinephrine, 1 child developed nausea, pallor, and muscle twitching. CONCLUSIONS: Despite expert coaching, because of the number of epinephrine inhalations required and the bad taste of the inhalations, most children were unable to inhale sufficient epinephrine to increase their plasma epinephrine concentrations promptly and significantly. Therefore, we urge caution in recommending epinephrine inhalation as a substitute for epinephrine injection for out-of-hospital treatment of anaphylaxis symptoms in children.

Administration, Inhalation↗
PubMed2006

Sublingual epinephrine tablets versus intramuscular injection of epinephrine: dose equivalence for potential treatment of anaphylaxis.

BACKGROUND: Epinephrine autoinjectors are underused in the emergency treatment of anaphylaxis in the community, perhaps in part because of fear of needles. OBJECTIVES: To determine the sublingual epinephrine dose from a novel fast-disintegrating tablet required to achieve epinephrine plasma concentrations (EPPCs) similar to those obtained after epinephrine 0.3 mg intramuscular injection. METHODS: In a prospective 5-way crossover study, sublingual tablets containing epinephrine 0, 10, 20, and 40 mg, and epinephrine 0.3 mg intramuscular in the thigh (EpiPen) were compared in a validated rabbit model. Blood samples were collected before dosing and 5, 10, 15, 20, 30, 40, 60, 90, 120, 150, and 180 minutes afterward. EPPCs were measured by using high-performance liquid chromatography-electrochemical detection. Pharmacokinetic parameters were calculated by using WinNonlin. RESULTS: The area under the curve (AUC), maximum concentration (C(max)), and time at which C(max) was achieved (T(max)) did not differ significantly (P > .05) after epinephrine 40 mg (AUC = 1861 +/- 537 ng/mL/min, C(max) = 31.0 +/- 13.1 ng/mL, and T(max) = 9 +/- 2 minutes) and epinephrine 0.3 mg intramuscular (AUC = 2431 +/- 386 ng/mL/min, C(max) = 50.3 +/- 17.1 ng/mL, and T(max) = 21 +/- 5 minutes). The AUC after tablets containing epinephrine 0 mg (AUC = 472 +/- 126 ng/mL/min), epinephrine 10 mg (AUC = 335 +/- 152 ng/mL/min), and epinephrine 20 mg (AUC = 801 +/- 160 ng/mL/min) did not differ significantly from each other, but were significantly lower (P < .05) than the AUC after epinephrine 0.3 mg intramuscularly. CONCLUSION: Sublingual administration of epinephrine 40 mg from this tablet formulation resulted in EPPCs similar to those obtained after epinephrine 0.3 mg intramuscular injection in the thigh. CLINICAL IMPLICATIONS: For treatment of anaphylaxis in the community, self-injectable epinephrine is underused. This novel, fast-disintegrating epinephrine tablet formulation for sublingual administration is a feasible alternative that warrants further development.

Administration, Sublingual↗
PubMed1995

Effects of aging on epinephrine secretion and regional release of epinephrine from the human heart.

In contrast to the sympathetic nervous system, which is activated by aging in at least some sympathetic nervous outflows, epinephrine release from the adrenal medulla appears to be either normal or low in the elderly. Using isotope dilution methodology, we studied the effect of aging on the secretion of epinephrine in 19 men, aged 20-30 yr, and 15 men, aged 60-75 yr. Measurements were made both at rest and during the application of laboratory stressors, as diminished adrenal medullary responsiveness possibly contributes to the impairment of some cardiovascular and metabolic responses to stress described previously in the elderly. Epinephrine secretion at rest was lower in the older men (mean +/- SEM, 0.86 +/- 0.10 nmol/min) than in the younger men (1.45 +/- 0.17 nmol/min; P < 0.05). Due to 20% lower plasma epinephrine clearance in the older men (P < 0.01), the reduction in the plasma concentration of epinephrine (0.37 +/- 0.03 vs. 0.52 +/- 0.06 nmol/L; P = 0.06) was proportionally less than that in epinephrine secretion. In the younger men, epinephrine secretion doubled or tripled during mental stress, isometric exercise, and dynamic exercise. Epinephrine responses to the stressors were reduced in older men, being equivalent to only 44% (P < 0.05), 44% (P = 0.1), and 33% (P = 0.01) of the corresponding responses in the younger men. After uptake from plasma, in some circumstances epinephrine is released from sympathetic nerves as a cotransmitter, where it can augment the release of the major sympathetic transmitter, norepinephrine. We also measured regional extraadrenal release of epinephrine from the heart to test whether the previously described increased release of norepinephrine from the cardiac sympathetic nerves with aging might result from facilitator effects of epinephrine released as a cotransmitter. At rest, epinephrine was released from the heart (9.4 +/- 2.6 pmol/min) in older men only (P < 0.01) despite the fact that adrenal medullary secretion of epinephrine was reduced. Failure of epinephrine and norepinephrine spillover from the heart to increase in parallel in the elderly during the sympathetic excitation accompanying exercise suggested that epinephrine lay outside the sympathetic nerves, perhaps arising from extraneuronal synthesis in the heart. We have not yet tested whether extraneuronal, in contrast to neuronal, epinephrine release in the heart could contribute to the observed higher rates of norepinephrine release in the elderly.

Adult↗
PubMed1990

Naloxone enhances cardiac contractile responses to epinephrine without altering epinephrine uptake from plasma.

Naloxone potentiates the inotropic effect of selected beta-agonists in the canine isolated heart. This could be accomplished by elevating circulating catecholamines through a reduction in their disposal or by the facilitation of events at or subsequent to the cardiac beta-receptor. To evaluate the first hypothesis, epinephrine was infused intravenously into a blood-perfused isolated heart-lung preparation. Catecholamines were determined and myocardial and pulmonary epinephrine uptakes were calculated. Naloxone enhanced the inotropic effect (peak +dP/dt) during epinephrine infusion. Coronary blood flow and coronary venous epinephrine concentrations were also elevated after naloxone. Calculated myocardial and pulmonary uptake of epinephrine were, however, unaltered by naloxone. The increased coronary sinus epinephrine after naloxone was evaluated further in experiments redesigned to eliminate the influence of changing coronary blood flow. Epinephrine was infused into the left common coronary and coronary blood flow as maintained constant, 100% above the resting flow rate. Naloxone enhanced the contractile response to epinephrine without altering coronary artery or coronary sinus epinephrine concentrations or myocardial epinephrine uptake. By comparison, corticosterone, an extra-neuronal uptake inhibitor, also potentiated the inotropic effect of infused epinephrine under identical conditions. However, corticosterone was accompanied by a significant increase in coronary sinus epinephrine concentration and a decrease in myocardial epinephrine uptake. We therefore concluded that the ability of naloxone to enhance the inotropic effect of epinephrine is not mediate through an increase in plasma epinephrine concentration secondary to a decrease in the disposal of circulating catecholamines.

Animals↗
PubMed1979

Clinical comparison of dipivalyl epinephrine and epinephrine in the treatment of glaucoma.

Dipivalyl epinephrine, 0.1%, though slightly less effective in decreasing intraocular pressure, showed significantly fewer side effects than epinephrine hydrochloride, 2%. Seventeen patients with symmetrically increased intraocular pressures who completed a six-month double-masked crossover study showed a significant decrease in intraocular pressure averaging 23.7% for dipivalyl epinephrine over the entire study and 27.4% for epinephrine. In the first treatment period, dipivalyl epinephrine was slightly less effective than epinephrine. In the second treatment period, dipivalyl epinephrine was statistically less effective than epinephrine. Two of the original 25 patients were dropped from the study because of epinephrine allergy or intolerance, one had uncontrolled pressures with either drug, and five failed to maintain adequate follow-up. Complaints of side effects such as burning and irritation occurred much more frequently in eyes receiving epinephrine (24%) than dipivalyl epinephrine (3%). Mild mydriasis occurred with each drug, averaging +0.65 mm with dipivalyl epinephrine and +0.55 mm Hg with epinephrine. No effect on blood pressure or pulse rate was found for the two drugs.

Adult↗
PubMed1983

Epinephrine is a hypophosphatemic hormone in man. Physiological effects of circulating epinephrine on plasma calcium, magnesium, phosphorus, parathyroid hormone, and calcitonin.

The physiologic effects of epinephrine on mineral metabolism are not known. In six healthy men, insulin-induced hypoglycemia, a potent stimulus to endogenous epinephrine secretion, resulted in a decrement of 0.9+/-0.1 mg/dl (mean+/-SE, P < 0.001) in serum inorganic phosphorus and smaller increments in magnesium and total and ionized calcium. Plasma immunoreactive parathyroid hormone (iPTH) decreased and plasma immunoreactive calcitonin (iCT) increased appropriately with the increments in calcium and magnesium. We wished to determine to what extent these changes in mineral metabolism might be attributable to epinephrine. Therefore, in the same protocol, we infused the hormone over 60 min in these six men, in doses that resulted in steady-state plasma epinephrine concentrations ranging from 52 to 945 pg/ml (levels that span the physiologic range), for a total of 25 studies. Serum ionized calcium, iPTH, and iCT concentrations were unaltered by these physiologic elevations of plasma epinephrine. However, epinephrine resulted in dose-dependent decrements in serum inorganic phosphorus of 0.6+/-0.1 mg/dl (P < 0.005) for the highest epinephrine infusion rate. The plasma epinephrine concentration threshold for this hypophosphatemic effect was approximately 50-100 pg/ml. Thus, the sensitivity of the hypophosphatemic response to epinephrine is comparable to that of the cardiac chronotropic, systolic pressor, and lipolytic responses to epinephrine, and considerably greater than that of the diastolic depressor, glycogenolytic, glycolytic, and ketogenic responses to the hormone in human beings. In view of its rapidity, the hypophosphatemic effect of epinephrine is probably the result of a net shift of phosphate from the extracellular compartment to intracellular compartments. We suggest that it is a direct effect of epinephrine, in that it is not mediated by changes in availability of the primary regulatory hormones PTH and CT, although indirect effects mediated by changes in other hormones, such as insulin, cannot be excluded. The hypophosphatemic response is also not attributable to increments in plasma calcium. These data indicate that epinephrine in physiologic concentrations is a hypophosphatemic hormone in man.

Adult↗
PubMed1997

Signal transduction system in epinephrine stimulated platelets; comparison between epinephrine sensitive and insensitive platelets.

We recently reported the high prevalence of impaired platelet responsiveness only to epinephrine in healthy Japanese. This abnormality was associated with a 50% decrease in the number of alpha 2-adrenergic receptors. Platelets from non-responders (NR) do not undergo secondary platelet aggregation even after exposure to 100 microM epinephrine, but they can potentiate the effect of ADP to provoke platelet aggregation. To further define the nature of the defect and to delineate controversial steps of epinephrine stimulated signal transduction, a signaling pathway of epinephrine was investigated in platelets from NR and R(normal responder to epinephrine). In a unique particle counting apparatus, epinephrine initially triggered the formation of small platelet aggregates composing of 10-1000 cells from both R and NR, but the aggregates became larger (4600 > cells) only in platelets from R. Thus, platelets from NR lack the ability to form larger aggregates. A similar defect was reproduced by treating normal platelets with aspirin. In the presence of fibrinogen, platelets from NR lacked phospholipase A2 activation, determined by arachidonic acid liberation in the presence of inhibitors to cyclooxygenase and lipoxygenase. In the absence of fibrinogen, aggregation and phospholipase A2 activation were not evident in R and NR. The surface expression of GPIIb/IIIa was markedly decreased in platelets from NR after stimulation by epinephrine, in comparison with those from R. The resting level and epinephrine stimulated increase in cAMP were not significantly different between NR and R. Incubating R platelets with a half saturating dose of yohimbine rendered them insensitive to epinephrine. These results indicated that the impaired platelet aggregation induced by epinephrine was due to the impaired surface exposure of glycoproteins GPIIbIIIa integral to the activation of phospholipase A2, which requires the full and normal occupancy of the alpha 2-adrenergic receptor by epinephrine.

Adenosine Triphosphate↗
PubMed1956

The role of epinephrine in the reactions produced by the endotoxins of gram-negative bacteria. II. The changes produced by endotoxin in the vascular reactivity to epinephrine, in the rat mesoappendix and the isolated, perfused rabbit ear.

The effects of endotoxin on the epinephrine reactivity of blood vessels in the rat mesoappendix have been studied. Following intravenous injection of a relatively small, sublethal dose of endotoxin, the terminal arterioles and venules exhibited greatly augmented and prolonged vasoconstrictor responses to epinephrine and norepinephrine. Hyperreactivity became evident within 30 minutes after injection of endotoxin, and persisted for as long as 6 hours. After larger doses of endotoxin, sufficient to cause illness or death, the vascular hyperreactivity to epinephrine was of briefer duration, and was followed by a stage of increasing hyporeactivity reaching levels much below normal. With lethal doses, the terminal arterioles and venules became completely refractory to epinephrine, while heightened reactivity persisted in the larger arteries and veins. The end result was pooling of stagnant blood in distended capillaries and venules, accompanied by the appearance of petechiae. Topical applications of epinephrine during this stage were followed promptly by an increase in petechial hemorrhage at the site of testing. Rats which were rendered tolerant to the lethal effect of endotoxin, by repeated daily injections of small doses, developed resistance to the effects of endotoxin on epinephrine reactivity. Neither hyperreactivity nor hyporeactivity to epinephrine were demonstrable in these animals, nor were spontaneous abnormalities of blood flow or petechial hemorrhages observed in the mesoappendix. Analogous results were obtained in perfusion studies of the vessels of the isolated rabbit ear. Perfusion of small amounts of endotoxin was followed within a few minutes by potentiation of epinephrine reactivity. Larger doses caused complete reversal of this effect, to such an extent that epinephrine now produced marked degrees of vasodilation. The possible meaning of these observations in the interpretation of the endotoxin-epinephrine skin lesions described in the preceding paper is discussed. It is suggested that abnormal reactions to epinephrine or norepinephrine in the tissues of intact animals may represent a basic mechanism in the intoxicating and tissue-damaging properties of endotoxin.

Animals↗
PubMed2004

Plasma metanephrine levels are decreased in type 1 diabetic patients with a severely impaired epinephrine response to hypoglycemia, indicating reduced adrenomedullary stores of epinephrine.

A defective epinephrine response to hypoglycemia is a common disorder in type 1 diabetes. We assessed the role of the adrenomedullary capacity to secrete epinephrine in this disorder by measuring plasma metanephrine levels in affected type 1 diabetic patients compared with those in matched nondiabetic controls. Metanephrine is formed from epinephrine that leaks from adrenomedullary storage vesicles by catechol-O-methyl transferase (COMT) and is continuously released into the circulation. Thus, plasma metanephrine levels reflect adrenomedullary epinephrine content and, provided there is normal COMT activity, the adrenomedullary capacity to secrete epinephrine. Diabetic patients had approximately 25% lower plasma metanephrine levels than controls (0.18 +/- 0.09 vs. 0.24 +/- 0.02 nmol/liter; P = 0.012), whereas plasma epinephrine, norepinephrine, and normetanephrine levels were comparable between patients and controls. In response to hypoglycemia, the increments in plasma epinephrine and plasma metanephrine levels were both significantly lower in diabetic patients than in controls (P < 0.001), but the increase in plasma metanephrine as a percentage of the increase in plasma epinephrine was identical, indicating similar COMT activity. We conclude that type 1 diabetic patients with an impaired epinephrine response to hypoglycemia have lower plasma metanephrine levels than matched controls, reflecting decreased adrenomedullary stores of epinephrine and indicating reduced adrenomedullary capacity to secrete epinephrine.

Adrenal Medulla↗
PubMed1980

Induction of the fibrinogen receptor on human platelets by epinephrine and the combination of epinephrine and ADP.

The capacity of epinephrine alone and the combination of low dose epinephrine and ADP to support the binding of fibrinogen to washed human platelets has been examined, 125I-Fibrinogen was bound to epinephrine-stimulated platelets, but 90 min were required to achieve maximal binding at 22 degrees C in contrast to 20 to 30 min with ADP. The overall rate of interaction appeared to reflect the slow binding of fibrinogen to epinephrine-stimulated platelets as opposed to the rate of stimulation of the cell. Divalent ions were required for binding of fibrinogen to epinephrine-stimulated platelets, and both calcium and magnesium supported binding with a prolonged time course. Fibrinogen binding was maximally supported by 20 to 30 microM epinephrine. The combination of low dose epinephrine (5 microM) and low dose ADP (0.5 microM), which acted synergistically to induce platelet aggregation, supported the rapid (10 min) binding of fibrinogen to platelets. With 4 microM epinephrine, more fibrinogen bound per platelet at all ADP doses than with ADP alone. With all the stimuli, saturable binding of fibrinogen to the platelet was observed, and Scatchard plots were linear, yielding very similar apparent association constants. The number of molecules bound per cell was stimulus-dependent, with 30 microM epinephrine inducing the binding of fewer fibrinogen molecules per cell (mean = 20,400) than 10 microM ADP (mean = 35,900) or the combination of 5 microM epinephrine + 0.5 microM ADP (mean = 43,600). The participation of endogenous ADP in fibrinogen binding to epinephrine-stimulated platelets was suggested since enzymes which remove ADP, apyrase, and creatine phosphate/creatine phosphokinase, and the ADP analogue, 2-chloroadenosine, completely inhibited the binding of fibrinogen to the platelet.

Adenosine Diphosphate↗
PubMed1999

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

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

Adolescent↗
PubMed1998

Reduced epinephrine clearance and glycemic sensitivity to epinephrine in older individuals.

To test the hypothesis that glycemic sensitivity to epinephrine is reduced in older individuals and to assess the impact of a sedentary lifestyle on responses to the hormone, we performed 30-min sequential intravenous infusions of epinephrine (0, 41, 82, 164, 246, and 328 pmol. kg-1. min-1) in young (n = 10) and older (n = 23) healthy subjects. We performed these again after 12 mo of physical training, which raised peak O2 consumption from 24.4 +/- 1.0 to 30.4 +/- 1.4 ml. kg-1. min-1 (P < 0.01) in most of the older subjects (n = 21). During epinephrine infusions, plasma epinephrine concentrations were higher (P = 0.0001) in older than in young subjects (e.g., final values of 7,280 +/- 500 vs. 4,560 +/- 380 pmol/l, respectively), indicating that the clearance of epinephrine from the circulation was reduced in the older individuals. Plasma epinephrine concentration-response curves disclosed reduced glycemic sensitivity to the hormone in the older subjects (P = 0.0001), a finding plausibly attributed to increased sympathetic neural activity, as evidenced here by higher plasma norepinephrine concentrations (P = 0.0001) in the older subjects and consequent desensitization of cellular responsiveness to catecholamines. Training did not correct reduced epinephrine clearance, reduced glycemic sensitivity to epinephrine, or raised norepinephrine levels. We conclude that aging is associated with reduced clearance of epinephrine from the circulation and reduced glycemic sensitivity to epinephrine, the latter plausibly attributed to an age-associated increase in sympathetic neural norepinephrine release. These age-associated changes are not the result of a sedentary lifestyle.

3-Hydroxybutyric Acid↗