Arterial Epinephrine Levels Research Articles

Anesthetic regimen effects on a pediatric porcine model of asphyxial arrest

The effects of three anesthetic regimens on an established model of pediatric porcine hypoxic-hypercarbic arrest were examined. Twenty-four preadolescent miniature piglets were paralyzed, mechanically ventilated and anesthetized with one of three regimens: IM+IV pentobarbital ( n=8); IM+IV ketamine ( n=8); or IM ketamine+inhaled isoflurane ( n=8). Asphyxial cardiopulmonary arrest was induced and, after an 8 min cardiac arrest nonintervention interval, a standardized protocol of manual CPR with mechanical ventilation was performed. Outcome variables included incidence of ventricular fibrillation, time to cardiac arrest, endogenous plasma epinephrine levels and arteriovenous epinephrine gradients. IV Ketamine anesthesia produced the highest incidence of ventricular fibrillation ( P<0.01 vs. pentobarbital and isoflurane). Time to asphyxia induced cardiac arrest was greatest for the pentobarbital group ( P<0.05 vs. ketamine and isoflurane). During induction of asphyxial cardiac arrest (low cardiac flow), endogenous venous epinephrine accumulation was highest in the pentobarbital anesthetized group ( P<0.05). After 8 min of untreated cardiac arrest and 1 min of CPR (low flow), arterial epinephrine levels were highest in the ketamine group ( P<0.05). Endogenous epinephrine gradients were venous>arterial in all groups at the end of the 8 min cardiac arrest non-intervention interval (no flow). After 1 min of CPR, the gradients had either equalized or reversed to arterial>venous in all groups except for pentobarbital. As designed and expected, return of spontaneous circulation did not occur in any animal. We conclude that, in developing models of porcine asphyxial cardiopulmonary arrest and resuscitation to simulate pediatric human arrest, variations in anesthetic regimen produce significant differences in parameters that are important to consider: time to asphyxia induced cardiac arrest, fibrillation threshold, plasma epinephrine level and arteriovenous epinephrine gradient. Anesthetic effects need to be carefully considered and clearly explained to facilitate the interpretation of studies of interventions in cardiopulmonary arrest and resuscitation.

The effect of transcutaneous electrical nerve stimulation (TENS) on catecholamine metabolism during pacing-induced angina pectoris and the influence of naloxone

Two invasive studies (invasive study I and invasive study II) showed positive effects of transcutaneous electrical nerve stimulation (TENS) in pacing-induced angina pectoris in terms of increased tolerance to pacing, improved lactate metabolism and less anginal pain. Invasive study I demonstrated a decrease in left ventricular afterload by TENS treatment as reflected by a fall in systolic blood pressure and this fact was thought to be explained by reduced sympathetic activity since arterial levels of epinephrine and norepinephrine dropped during TENS in TENS responders. In invasive study II, the influence of naloxone on the effects of TENS in pacing-induced angina pectoris was studied in 11 patients with severe coronary artery disease. The patients were catheterized and treated with TENS on 2 occasions; one with a single intravenous (i.v.) dose of saline as placebo and one with a single i.v. dose of 50 mg naloxone, double-blind, in random order. Treatment with TENS increased tolerance to pacing ( P < 0.01 with placebo and P < 0.01 with naloxone, respectively) and improved lactate metabolism ( P < 0.05 with placebo and P < 0.01 with naloxone, respectively). The positive effects of TENS were thus reproducible and not reversed by single i.v. doses of naloxone. The results of this study indicate that the effects of TENS on the heart are not mediated by beta-endorphin but do not exclude activation of more short-acting opioids like delta or kappa receptor agonists (met-enkephalin and/or dynorphin) since naloxone has a low affinity for these receptors. It is also possible that non-opioid mechanisms are of importance. However, this study did not exhibit any data that confirmed the hypothesis that the effects of TENS in angina pectoris can be explained by a reduced sympathetic activity, since the arterial levels of epinephrine and norepinephrine did not change and the systolic blood pressure did not decrease during TENS treatment.

Regional adrenal blood flow during hypoxia in anesthetized, ventilated dogs

The effect of hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH) on adrenal medullary (MQ) and cortical (CQ) blood flow (radiolabeled microsphere technique) was studied in pentobarbital sodium-anesthetized, mechanically ventilated dogs. Animals were exposed to 60 min of hypoxia (arterial O2 content 8 vol%) induced by adding either nitrogen (HH, n = 6) or carbon monoxide (COH, n = 6) to the inspired gas. Whole adrenal Q and CQ increased by 70 and 50%, respectively, with HH but were unchanged during COH. MQ, however, increased threefold during both HH and COH. HH and COH both increased arterial levels of epinephrine, corticosteroids, and adrenocorticotropic hormone (ACTH). To determine whether the increase in CQ during HH was because of HH-induced increases in mean arterial blood pressure (MAP, approximately 20 mmHg), an additional group of animals (n = 6) was exposed to HH but had MAP maintained at control levels using a pressurized-bottle system. MAP control did not alter the CQ response to HH. We conclude that MQ appears to be associated with medullary secretory activity during hypoxia and that HH and COH stimulate adrenal medullary secretion equally. In contrast, CQ increases only with HH, despite similar increases in ACTH and corticosteroid levels during HH and COH, suggesting that an alternative mechanism is responsible for increased cortical blood flow during HH.

Pulmonary vascular responses to forebrain stimulation in the cat.

The effects of forebrain stimulation on the pulmonary vascular bed were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was raised to a high steady level, direct electrical stimulation of the forebrain elicited a biphasic change in lobar arterial pressure. The response was characterized by an initial transient increase in lobar arterial pressure that was followed by a prolonged secondary decrease in pressure. When a delay coil was added to the extracorporeal perfusion circuit, the secondary vasodilator response was separated into initial brief and delayed prolonged components, suggesting that it was mediated in part by the release of a humoral factor. The entire response to forebrain stimulation was abolished by cervical cord section or freezing. The initial constrictor response and early brief dilator response were not blocked by classic pharmacological blocking agents. The delayed humorally mediated vasodilator response was blocked by propranolol or ICI 118551, indicating that it was mediated by a circulating factor with beta 2-stimulating properties. The delayed vasodilator response was associated with a large increase in arterial epinephrine levels, and this rise in plasma epinephrine was not altered by propranolol. The present data suggest that electrical stimulation of the forebrain causes a prolonged pulmonary vasodilator response that is mediated by way of a descending pathway, which results in a large rise in arterial epinephrine levels.

Potent mental stress and insulin absorption in normal subjects.

Effects of mental stress (a 20-min modified Stroop's color-word conflict test; CWT) on the absorption of 125I-labeled soluble human insulin (10 U s.c. in the thigh 60 min before CWT) and on subcutaneous adipose tissue blood flow (ATBF; 133Xe clearance); heart rate (HR); arterial blood pressure (BP); and arterial levels of epinephrine (Epi), norepinephrine (NE), and glycerol were studied in 11 healthy subjects. Insulin absorption was measured as elimination of radioactivity (external gamma-counting) and as appearance of plasma immunoreactive insulin (IRI). The glucose-clamp technique was used to maintain normoglycemia. Identical measurements were performed during a control day without CWT. HR and mean BP increased markedly (35 +/- 5 beats/min and 30 +/- 3 mmHg) during CWT despite only minor elevations in plasma catecholamines. Thus, arterial plasma Epi rose from 0.18 +/- 0.03 to 0.82 +/- 0.17 nM (P less than .01) and NE from 0.94 +/- 0.09 to 1.69 +/- 0.18 nM (P less than .001). ATBF showed a biphasic response, with a 100% elevation during CWT followed by a decrease and a second peak of similar magnitude approximately 0.5 to 1 h after CWT. Blood glycerol was approximately doubled during CWT and remained elevated during recovery. Despite these changes, insulin absorption was unaltered during and after stress. Thus, elimination rates of 125I, plasma IRI levels, and amounts of glucose needed to maintain normoglycemia were all similar during the stress and control days. These results suggest that absorption of soluble insulin from subcutaneous injection sites in the thigh is unaltered during potent mental stress in healthy subjects despite a considerable and prolonged increase in ATBF.

Plasma catecholamines in conscious rabbits after central administration of vasopressin

Arterial levels of epinephrine (E) were significantly raised for all times sampled, after intracerebroventricular (i.c.v.) injection of arginine vasopressin (AVP) (1 nmol) into conscious rabbits. Venous levels of norepinephrine (NE) were significantly raised within the first 4 min after a similar i.c.v. injection of AVP. The significant increases in arterial E and venous NE correspond in time and therefore could account for changes in heart rate and blood pressure elicited by centrally injected AVP. Therefore, AVP could influence cardiovascular function by increasing the activity of the sympatho-adrenomedullary system.

Extraction of epinephrine and norepinephrine by the dog pancreas in vivo

This study determined the fractional extraction of epinephrine and norepinephrine by the in situ dog pancreas. Plasma samples for epinephrine measurements were taken simultaneously from the femoral artery and the superior pancreaticoduodenal vein. Pancreatic extraction of epinephrine was 73 ± 5% when basal arterial epinephrine levels were 380 ± 93 pg/mL, 76 ± 4% when arterial levels were 896 ± 123 pg/mL (epinephrine infused intravenously at 20 ng/kg/min), and 84 ± 1% when arterial levels were 2,956 ± 414 pg/mL (epinephrine infused intravenously at 80 ng/kg/min) suggesting that the process of epinephrine extraction by the pancreas is not saturable over this range. During a similar sampling protocol, norepinephrine was infused intravenously at 4 μg/kg/min; pancreatic extraction of norepinephrine was then 65 ± 7% when arterial norepinephrine levels were 107,000 ± 28,000 pg/mL. In separate experiments, lower rates of norepinephrine (12 to 1,200 ng/min) were infused directly into the pancreatic artery and pancreatic norepinephrine extraction was calculated; it ranged between 66% and 75%. Because the pancreas produces as well as extracts norepinephrine, a third technique was required to determine pancreatic norepinephrine extraction at the lower endogenous levels of norepinephrine; 3H-norepinephrine was infused intravenously and the arteriovenous difference of 3H-norepinephrine was measured. Fractional extraction of 3H-norepinephrine was 74 ± 4% both in the basal state (arterial norepinephrine level = 202 ± 44 pg/mL) and during systemic, glucopenic, stress induced by 2-deoxy-glucose (arterial norepinephrine level = 636 ± 70 pg/mL). These data suggest that also the norepinephrine extraction process by the pancreas is not sarurable. Further, since the pancreatic extraction of norepinephrine is so avid, these data suggest that measurement of the arteriovenous concentration difference of endogenous norepinephrine alone will markedly underestimate local norepinephrine spillover. Correcting these measurements for the extraction would, however, provide an index of the endogenous activity of pancreatic adrenergic nerves. Finally, this study also determined whether pancreatic catecholamine extraction is altered by α-or β-adrenoceptor antagonists; phenoxybenzamine was found to reduce the extraction of both epinephrine ( P < .001) and norepinephrine ( P < .05) whereas propranolol did not. Thus, one must consider how changes of pancreatic catecholamine extraction might alter the interpretation of experiments using α-adrenoceptor antagonists to study local norepinephrine release or catecholamine effects on pancreatic hormone secretion. In summary, (1) at steady state 60% to 80% of either epinephrine or norepinephrine is extracted in one pass by the dog pancreas, (2) this process of extraction appears nonsaturable, and (3) the pancreatic extraction of catecholamines is impaired by the α-adrenoceptor antagonist phenoxybenzamine, but not by the β-adrenoceptor antagonist propranolol.

Catecholamine metabolism during pacing-induced angina pectoris and the effect of transcutaneous electrical nerve stimulation

The arterial levels of norepinephrine and epinephrine were estimated in 14 patients with severe coronary artery disease in order to assess the catecholamine metabolism during pacing-induced angina pectoris and to evaluate the effects of transcutaneous electrical nerve stimulation (TENS). Arterial levels of epinephrine and norepinephrine increased significantly during pacing to angina pectoris ( p < 0.05 and p < 0.001, respectively), indicating that maximal atrial pacing induced an increase in sympathetic tone. At the corresponding pacing rate during TENS, myocardial lactate production was improved ( p < 0.01) and the ST segment depression was less pronounced ( p < 0.05). The maximal pacing rate during TENS was 141 ± 24 compared to 123 ± 19 ( p < 0.01) and the heart rate-blood pressure product was also significantly higher ( p < 0.01), suggesting an elevation of the anginal threshold by TENS. Systemic vascular resistance and systolic blood pressure were significantly reduced (both p < 0.01). These beneficial results may be caused by a decrease in left ventricular afterload as reflected by a fall in systolic blood pressure and may be explained by reduced sympathetic activity. TENS may decrease the sympathetic activity either directly or indirectly as a consequence of pain inhibition. This hypothesis is supported by the fact that arterial levels of epinephrine and norepinephrine dropped during TENS in TENS responders.

Indices of sympathetic vascular innervation in sympathectomized patients

We measured arterial and venous plasma catecholamines and used laser-Doppler flowmetry to measure cutaneous microcirculatory flow in the sympathectomized and in the intact limbs of 3 patients who had undergone regional sympathectomies. Venous concentrations of norepinephrine, the sympathetic neurotransmitter, exceeded arterial concentrations in the intact limbs—a normal finding—but invariably were less than arterial in the sympathectomized limbs of the same patients, both during baseline conditions and during sympathetic stimulation using tilt, standing and the cold pressor test (mean arteriovenous decrement about 40%). Arterial epinephrine levels exceeded venous levels with or without sympathectomy. Skin microvascular flow rapidly decreased during the cold pressor test and the Valsalva maneuver in the intact but not in the sympathectomized limbs, and spontaneous flow oscillations occurred in the sympathectomized limbs. The results suggest that an arteriovenous increment in plasma norepinephrine reflects local release of norepinephrine from sympathetic nerve endings, whereas removal of circulating catecholamines can occur with or without sympathetic neural impulses. Laser-Doppler flowmetry can measure reflexive sympathetically mediated responses of skin microvascular flow and so can detect sympathetic denervation. Spontaneous oscillations in this flow may not depend exclusively on oscillations in the activity of the sympathetic microvascular innervation.

Facultative thermogenesis induced by carbohydrate: a skeletal muscle component mediated by epinephrine

In addition to the obligatory thermogenesis due to processing and storage, carbohydrate ingestion is accompanied by a facultative thermogenesis mediated by catecholamines via beta-adrenoceptors. The anatomical origin of facultative thermogenesis has hitherto not been determined. The possible involvement of skeletal muscle was examined in lean, healthy subjects by measuring the response in forearm oxygen consumption to an oral glucose load. The study demonstrates an early component of skeletal muscle thermogenesis coinciding with the local glucose uptake, followed by a late facultative thermogenesis. The arterial epinephrine concentration increased to a maximum of 200% above base-line values 4 h after glucose. This value greatly exceeds the physiological threshold for the thermogenic action of epinephrine. In forearm venous blood the corresponding increase in epinephrine was only approximately 50% due to enhanced peripheral extraction, which accompanies an increase in arterial epinephrine levels. Due to venous sampling previous studies have overlooked the magnitude of the late postglucose increase in arterial epinephrine, and its potential thermogenic effect has been disregarded. The facultative thermogenesis in skeletal muscle may be of importance for the regulation of body weight in humans.

Endogenous catecholamine levels in chronic heart failure. Relation to the severity of hemodynamic abnormalities

Plasma free epinephrine, norepinephrine, and dopamine concentrations were determined in 48, 63, and 45 patients, respectively, with overt congestive heart failure, and compared with those in 26 patients with stable angina but without heart failure. Systemic hemodynamic values were determined to assess the severity of heart failure. Arterial epinephrine levels were not different between patients with heart failure (73 ± 92 pg/ml) and patients without heart failure (55 ± 73 pg/ml). In patients with congestive heart failure, norepinephrine (665 ± 510 pg/ml, mean ± SD) and dopamine (407 ± 405 pg/ml) levels were significantly higher than in patients with stable angina without heart failure (norepinephrine 184 ± 136 pg/ml, p <0.001, and dopamine 197 ± 259 pg/ml, p <0.02). However, in patients with congestive heart failure, the plasma norepinephrine levels did not correlate with cardiac Index (r = 0.21, p = NS), pulmonary capillary wedge pressure (r = 0.11, p = NS), mean arterial pressure (r = 0.11, p = NS), or systemic vascular resistance (r = 0.18, p = NS). Similarly, there was no correlation between dopamine levels and the hemodynamic abnormalities In patients with congestive heart failure. These findings suggest that although endogenous norepinephrine and dopamine levels are frequently elevated In patients with heart failure, reflecting enhanced sympathetic activity, catecholamine levels do not reflect the severity of heart failure.

Nitrous Oxide Markedly Increases Cerebral Cortical Metabolic Rate and Blood Flow in the Goat

Studies to date on the influence of N2O on cerebral blood flow (CBF) and metabolism in dogs, rodents, and humans have produced conflicting results. In the present study the authors have employed techniques in the awake, freely breathing nonstressed goat that allowed the authors to 1) serially obtain rapidly frozen cerebral cortical biopsy specimens (for labile metabolite assay) and 2) measure changes in cerebral O2 metabolism (CMRO2) and total and regional CBF (rCBF). Thus, with each animal utilized as its own control, the authors studied N2O effects on the above variables. Two determinations of the effects of 1 h of N2O (70% via a mask) on these variables were performed on each animal. Following introduction of N2O, PaCO2 and arterial blood pressure did not change, but arterial epinephrine levels declined over the 60-min period. Total CBF increased in the first 5 min of N2O exposure, reached a maximum of 165% control at 15 min, and then decreased to 143% control at 60 min. rCBF evaluations showed that much of this CBF increase was confined to cerebral cortical structures (188-246% control at 60 min). Over the same period cortical CMRO2 increased to 170% of control. No appreciable changes in the levels of high-energy phosphates or glycolytic intermediates were found at 60 min of N2O. The authors attribute the described changes solely to the presence of N2O and not to sympathoadrenal influences, altered ventilation, or anything related to the experimental preparation, and they conclude that N2O (at least in goats) is associated with a marked cerebral cortical "activation".

Treatment of hypertension associated with head injury.

Arterial hypertension that occurs after severe head injury is characterized by elevation of systolic blood pressure, tachycardia, increased cardiac output, normal or decreased peripheral vascular resistance, and increased circulating catecholamines. The effects of two drugs used in the management of hypertension, propranolol and hydralazine, on these indices of cardiovascular function were examined in six head-injured patients. Both drugs effectively normalized blood pressure. However, hydralazine increased heart rate by 30%, cardiac index by 49%, left cardiac work by 21%, and pulmonary venous admixture by 53%, and was responsible for an increase in intracranial pressure or decreased compliance in two patients. Hydralazine produced no consistent change in arterial catecholamines. In contrast, propranolol decreased heart rate by 21%, cardiac index by 26%, left cardiac work by 35%, pulmonary venous admixture by 15%, and oxygen consumption by 18%. Propranolol decreased arterial epinephrine levels by 48% and norepinephrine levels by 28%. Propranolol appears to be a useful antihypertensive drug in the hyperdynamic head-injured patient because it normalizes blood pressure and the underlying hemodynamic abnormalities both by its beta-adrenergic blocking action and by decreasing circulating levels of catecholamines.

Different Norepinephrine Disappearance Rate in Venous and Arterial Plasma in Man

The disappearance of norepinephrine in both arterial (radial) and venous (antecubital) plasma was studied in five patients with mild essential hypertension following isometric exercise and norepinephrine infusion. Arterial levels of epinephrine throughout the study and of norepinephrine during norepinephrine infusion were consistently higher than venous levels, indicating that both amines are removed by passage through the forearm. Following infusion the disappearance rate of norepinephrine from arterial plasma was faster than from venous plasma. After isometric exercise there was a delay in fall of venous levels, consistent with a delayed efflux of norepinephrine from local tissues. Arterial plasma levels probably reflect total body contribution whereas venous plasma levels presumably reflect additional local removal and/or release from the forearm.

Release and clearance rates of epinephrine in man: importance of arterial measurements.

Previous estimates of catecholamine kinetics in human subjects have been based on the measurement of the catecholamine levels in forearm venous plasma. However, the use of forearm venous measurements may introduce considerable error, since venous catecholamine levels may primarily reflect metabolism in the organ drained rather than in the total body. In this study, arterial levels of epinephrine were found to significantly exceed forearm venous levels, both basally (mean +/- SEM, 71 +/- 13 vs. 50 +/- 7 pg/ml; n = 6; P less than 0.05) and during infusions of epinephrine [0.1 microgram/min (112 +/- 9 vs. 77 +/- 11 pg/ml; P less than 0.005) or 2 micrograms/min (862 +/- 71 vs. 437 +/- 66 pg/ml; P less than 0.001)]. During the 2 micrograms/min epinephrine infusion, arterial plasma norepinephrine rose from 191 +/- 37 to 386 +/- 78 pg/ml (P less than 0.001), while venous norepinephrine levels did not change significantly. Fractional extraction (arterial - venous + arterial X 100) of epinephrine across the forearm was 26 +/- 8% in the basal state and increased to 33 +/- 6% and further to 51 +/- 4% during the epinephrine infusions. The addition of propranolol (5 mg, iv, plus an 80 micrograms/min infusion) reduced fractional extraction from 51 +/- 4% to 35 +/- 5%. Whole body clearance of epinephrine, calculated from arterial measurements, was 33 +/- 3 ml/kg . min during the 0.1 microgram/min infusion and 35 +/- 3 ml/kg . min during the 2 micrograms/min epinephrine infusion, values 50% lower than the clearance rates calculated from venous measurements. Propranolol infusion resulted in a fall in whole body clearance to 20 +/- 2 ml/kg . min (P less than 0.001), suggesting that epinephrine clearance is partly dependent on a beta-adrenergic mechanism. Basal endogenous release rate (clearance X basal epinephrine level) was estimated to be approximately 0.18 microgram/min, a value much less than that reported in studies using venous measurements. We conclude that arterial rather than venous measurements should be used to estimate catecholamine kinetics in vivo.

Arterial-venous differences of plasma catecholamines in man

To investigate the relationship between forearm venous levels of catecholamines and systemic levels, simultaneous arterial and forearm vein blood samples were obtained from 14 subjects undergoing elective dental procedures and assayed with a sensitive and specific radioenzymatic assay. Baseline venous levels of norepinephrine were greater than arterial levels (305 ± 30 pg/ml versus 221 ± 18; ± SEM, p < .005). Conversely, arterial epinephrine levels were higher than venous (132 ± 17 pg/ml versus 80 ± 10; p < .005). There was a significant relationship between arterial and venous levels of both norepinephrine ( r = .77, p < .01) and epinephrine ( r = .67, p < .01). The arterial-venous epinephrine difference increased from the baseline value of 44 ± 14 pg/ml to 108 ± 16 ( p < .005) by 3 min after subcutaneous injection of epinephrine (18 μg), but the arterial-venous difference returned to 65 ± 24 by 5 min after injection ( p = NS versus baseline). These findings indicate that under the conditions of this study, forearm tissues produced more norepinephrine than they removed, but removed more epinephrine than they produced. Baseline venous and arterial levels were related; when epinephrine production was augmented, there was a short time lag for the venous epinephrine increase.