Endogenous Catecholamine Levels Research Articles

Endogenous Catecholamine Release in COVID-19 Related Acute Respiratory Distress Syndrome: Link between Enhanced Sympathetic Stimulation, Cardiac Dysfunction and Outcome

The aim of this study was to measure the serum levels of catecholamines in patients admitted to intensive care unit (ICU) with COVID-19-related acute respiratory distress syndrome (ARDS) and describe their relation with clinical, inflammatory and echocardiographic parameters. Serum levels of endogenous catecholamines (norepinephrine, epinephrine and dopamine) were measured at ICU admission. We enrolled 71 patients consecutively admitted to ICU due to moderate to severe ARDS. 11 patients (15.5%) died during the admission in ICU. Serum levels of endogenous catecholamines were significantly elevated. Norepinephrine levels were higher in those with RV and LV systolic dysfunction, higher CRP, and higher IL-6. Patients with higher mortality rate were those with norepinephrine values ≥ 3124 ng/mL, CRP ≥ 17.2 mg/dL and IL-6 ≥ 102 pg/mL. Univariable analysis by Cox proportional hazards regression modelling showed that norepinephrine, IL-6 and CRP had the highest risk of acute mortality. Multivariable analysis showed that only norepinephrine and IL-6 retained in the model. Marked increase of serum catecholamine levels is present during acute phase of critically ill COVID-19 and it is associated with inflammatory and clinical parameters.

Natural Sympathomimetic Drugs: From Pharmacology to Toxicology.

Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.

Catecholamine Toxicity After Craniotomy Evacuation Craniotomy and Evacuation of The Abscess

Increasing levels of endogenous catecholamines occur acutely to provide short-time adaptation to stressful conditions, known as the fight-or-fly response. Catecholamine toxicity requires multidisciplinary management. In this case, the patient is diagnosed with a brain abscess since birth. According of the history, physical examination and investigations, it was concluded that the diagnosis of epidural abscess with abscess evacuation craniotomy and PS ASA 2 (leukocytosis) with GA-ETT anesthesia. The operation is carried out with a duration of 4 hours. Vital sign monitoring obtained blood pressure sp108 – 125 62 - 90 mmHg, heart frequency 90 - 120 times per minute, 99% oxygen saturation. When in the recovery room, the patient experiences cardiac arrest, this is thought to result from catecholamine toxicity. Patients are treated as resuscitation in accordance with the algorithm of cardiac arrest in children. Patients experienced a response of spontaneous circulation (ROSC) and performed vital sign monitoring.

Abstract 13411: Vasodilatory Capacity With Regadenoson Myocardial Perfusion Imaging In Patients With End Stage Liver Disease

Introduction: The sensitivity and specificity of myocardial perfusion imaging in end stage liver disease (ESLD) patients ranges between 35-37% and 63-88%, respectively. Despite high levels of endogenous catecholamines and angiotensin, ESLD induced arterial vasodilation may exhaust the vasodilatory capacity of common pharmacologic stress agents. Reduced heart rate (HR) response to vasodilator stress test has been associated with increased major adverse cardiac events (MACE) in pre-transplant end stage renal disease patients but there is limited data in ESLD. We hypothesize that the hemodynamic response, measured as a change in HR and systolic blood pressure (SBP), during regadenoson stress test will be more robust when associated with low level exercise. Method: Forty-five subjects with ESLD referred for pre-transplant risk stratification were assigned to 1 of 3 groups: regadenoson alone or associated with low level treadmill or bicycle maneuver. Regadenoson was injected 2 minutes after low level exercise in the treadmill and bicycle groups. Myocardial perfusion images and hemodynamic changes were performed and interpreted as part of the standard clinical protocol. Results: There were 21 subjects in the regadenoson alone group, 10 in the low level treadmill group, and 14 in the bicycle maneuver group. There were no perfusion abnormalities in any of the groups and LVEF were greater than 50%. There was a statistically significant difference in HR response between the 3 groups (p = 0.015), but not in percentage SBP change between the 3 groups (p = 0.4). Pairwise comparison of regadenoson alone vs. low level treadmill percentage HR change showed statistical significance (p = 0.011). There was no MACE at 6-month follow-up. Conclusions: Low level exercise achieved a higher HR response than the other groups with a similar SBP response. The increased HR response may represent a more physiologic assessment of the true vasodilatory capacity remaining in ESLD patients.

Comparative study of dexmedetomidine vs. midazolam on plasma catecholamine levels and hemodynamics in patients with septic shock

To compare the effects of dexmedetomidine (DEX) and midazolam on the endogenous plasma catecholamine levels and the dosage of exogenous norepinephrine (NE) to maintain blood pressure in patients with septic shock. From January 2018 to December 2019, patients admitted to the department of critical care medicine of the Affiliated Hospital of Guizhou Medical University who needed invasive mechanical ventilation and had a stay of more than 48 hours in the intensive care unit (ICU) for septic shock and received DEX or midazolam for sedation were enrolled in this study. The hemodynamic data, arterial blood lactic acid (Lac) level, arterial blood gas analysis and vasoactive drug dose at 0, 12, 24, 48, 72 hours after entering the ICU were dynamically recorded, and the plasma catecholamine levels at 0, 24, 48 hours after entering the ICU were recorded. The acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score on ICU-admission were calculated. The parameters of prognosis were collected. A total of 24 patients were enrolled, 12 in the DEX group and 12 in the midazolam group. There were similar dynamic trends in heart rate (HR), central venous pressure (CVP), venous-arterial carbon dioxide pressure difference (Pv-aCO2), oxygenation index (PaO2/FiO2), and Lac level of patients between the two groups. Only the 12-hour CVP and 72-hour Pv-aCO2 in the DEX group were significantly higher than those in the midazolam group [CVP (mmHg, 1 mmHg = 0.133 kPa): 13±3 vs. 10±3, Pv-aCO2 (mmHg): 9.4±5.2 vs. 4.8±2.2, both P < 0.05], and the mean arterial pressure (MAP) of patients in the DEX group at 48 hours and 72 hours was significantly higher than that in the midazolam group (mmHg: 95±10 vs. 86±10, 96±9 vs. 88±7, both P < 0.05). There was no statistically significant difference in the duration of mechanical ventilation, ICU mortality or in-hospital mortality between the DEX group and the midazolam group [duration of mechanical ventilation (days): 5.6 (3.8, 9.5) vs. 10.5 (5.9, 15.0), ICU mortality: 16.7% vs. 33.3%, in-hospital mortality: 25.0% vs. 41.7%, all P > 0.05]. There was no significant difference in the dosage of propofol or sufentanil between the DEX group and the midazolam group [propofol (mg/kg): 0 (0, 9.35) vs. 4.07 (0, 13.75), sufentanil (μg/kg): 6.26 (4.90, 9.80) vs. 8.32 (3.52, 9.34), both P > 0.05]. The levels of plasma NE, dopamine and dobutamine in the DEX group at 48 hours were significantly lower than those in the midazolam group [NE (ng/L): 1 850.12 (342.16, 2 938.05) vs. 4 596.60 (3 310.56, 5 546.84), dopamine (ng/L): 119.10 (60.47, 200.71) vs. 275.40 (214.61, 418.88), dobutamine (ng/L): 51.20 (36.85, 75.59) vs. 98.97 (85.65, 107.10), all P < 0.05], but the amount of NE required to maintain MAP between 65 mmHg and 75 mmHg in the DEX group and the midazolam group was similar [μg/kg: 1 922 (1 170, 4 887) vs. 2 466 (2 043, 3 438), P > 0.05]. DEX can reduce plasma catecholamine levels in patients with septic shock more than midazolam, and does not increase the dose of exogenous NE, and has a smaller effect on hemodynamics in patients with septic shock than midazolam.

Quality of Death in Fighting Bulls during Bullfights: Neurobiology and Physiological Responses.

Simple SummaryFighting bulls that participate in bullfighting face energy and metabolic demands due to the high intensity and duration of the exercise performed. Under these conditions, specific corporal mechanisms, such as the acid–base balance, are affected, causing metabolic acidosis. However, fighting bulls also undergo muscular injuries, physiological changes, and high enzyme concentrations that reflect the stress to which they are subjected, and in some bulls, bullfights can trigger electrolytic imbalances that include hypercalcaemia, hypermagnesaemia, and hyperphosphataemia, exacerbated by muscular necrosis and myoglobinuria.During bullfights, bulls undergo physiometabolic responses such as glycolysis, anaerobic reactions, cellular oedema, splenic contraction, and hypovolemic shock. The objective of this review article is to present the current knowledge on the factors that cause stress in fighting bulls during bullfights, including their dying process, by discussing the neurobiology and their physiological responses. The literature shows that biochemical imbalances occur during bullfights, including hypercalcaemia, hypermagnesaemia, hyperphosphataemia, hyperlactataemia, and hyperglycaemia, associated with increased endogenous cortisol and catecholamine levels. Creatine kinase, citrate synthase, and lactate dehydrogenase levels also increase, coupled with decreases in pH, blood bicarbonate levels, excess base, partial oxygen pressure, and oxygen saturation. The intense exercise also causes a marked decrease of glycogen in type I and II muscle fibres that can produce myoglobinuria and muscular necrosis. Other observations suggest the presence of osteochondrosis. The existing information allows us to conclude that during bullfights, bulls face energy and metabolic demands due to the high intensity and duration of the exercise performed, together with muscular injuries, physiological changes, and high enzyme concentrations. In addition, the final stage of the bullfight causes a slow dying process for an animal that is sentient and conscious of its surroundings.

A perspective on the potential detrimental role of inflammation in pig orthotopic heart xenotransplantation.

There is a critical shortage of deceased human donor organs for transplantation. The need is perhaps most acute in neonates and infants with life-threatening congenital heart disease, in whom mechanical support devices are largely unsuccessful. If orthotopic (life-supporting) heart transplantation (OHTx) were consistently successful in the genetically engineered pig-to-nonhuman primate (NHP) model, a clinical trial of bridging with a pig heart in such patients might be justified. However, the results of pig OHTx in NHPs have been mixed and largely poor. We hypothesise that a factor is the detrimental effects of the inflammatory response that is known to develop (a) during any surgical procedure that requires cardiopulmonary bypass, and (b) immediately after an NHP recipient is exposed to a pig xenograft. We suggest that the combination of these two inflammatory responses has a direct detrimental effect on pig heart graft function, but also, and possibly of more importance, on recipient baboon pulmonary function, which further impacts survival of the pig heart graft. In addition, the inflammatory response almost certainly adversely impacts the immune response to the graft. If our hypothesis is correct, the potential steps that could be taken to reduce the inflammatory response or its effects (with varying degrees of efficacy) include (a) white blood cell filtration, (b) complement depletion or inactivation, (c) immunosuppressive therapy, (d) high-dose corticosteroid therapy, (e) cytokine/chemokine-targeted therapy, (f) ultrafiltration or CytoSorb hemoperfusion, (g) reduction in the levels of endogenous catecholamines, (h) triiodothyronine therapy and (i) genetic engineering of the organ-source pig. Prevention of the inflammatory response, or attenuation of its effects, by judicious anti-inflammatory therapy may contribute not only to early survival of the recipient of a genetically engineered pig OHTx, but also to improved long-term pig heart graft survival. This would open the possibility of initiating a clinical trial of genetically engineered pig OHTx as a bridge to allotransplantation.

Catecholamine Toxicity After Craniotomy and Evacuation of the Abscess

BACKGROUND: Brain abscess is a focal infection in the brain parenchyma, may be through direct extension or hematogenous. Brain abscess is a rare complication of neonatal meningitis that occurs in 1–4% of all cases. In infants and toddlers, bacterial meningitis or bacteremia is the major cause.&#x0D; CASE REPORT: In this case, the patient is diagnosed with a brain abscess since birth. According of the history, physical examination, and investigations, it was concluded the diagnosis of epidural abscess with abscess evacuation craniotomy and PS ASA 2 (leukocytosis) with GA-ETT anesthesia. The operation is carried out with a duration of 4 h. Vital sign monitoring obtained blood pressure 108–125/62–90 mmHg, heart frequency 90–120 times/min, and 99% oxygen saturation. When in the recovery room, the patient experiences cardiac arrest. Sudden cardiac arrest in children is a rare event. This is thought to result from catecholamine toxicity. Patient is treated as resuscitation in accordance with the algorithm of cardiac arrest in children. Patient experienced a response of spontaneous circulation and performed vital sign monitoring.&#x0D; CONCLUSION: Increasing levels of endogenous catecholamines occur acutely to provide short-time adaptation to stressful conditions. Catecholamine toxicity requires multidisciplinary management.

Development of a sensitive and fast method for detection of catecholamines and metabolites by HRMS

Variations in endogenous levels of catecholamines may be caused by changes in the organism, which are associated with the development of certain diseases by exogenous sources that are related to the intentional administration of some catecholamine. This study presents the development, validation and application of an analytical method to detect and to analyze the catecholamines and its metabolites simultaneously. The sample extraction consisted basically in hydrolysis and solid-phase extraction using a weak cation exchange functionalized polymeric sorbent cartridges. The catecholamines analysis was performed on orbitrap high resolution mass spectrometry HRMS-orbitrap equipped with electrospray. Modifications in different electrospray variables (S-lens, sheath gas flow and capillary temperature) were performed following the Doehlert experimental design (DOI). The validation parameters evaluated were repeatability, intermediate precision, matrix interference, limit of quantification, linearity, carryover and robustness. The most favorable conditions found according to the DOI for all analytes were S-lens fixed at 80 rf, sheath gas flow at 20 au and capillary temperature at 300 °C. The repeatability obtained from 100%, intermediate precision was 70%, matrix interference was observed, limit of quantification of the 5 ng·mL−1, linearity was 80%, robustness was 80% and carryover was not observed. DOI showed the most favorable conditions for the analysis of all the target compounds, contributing to the establishment of the method parameters. When applied in real samples, the method proved to be rapid, sensitive and selective even in the presence of urine interferents.

Feeding the critically ill obese patient: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE The objective of this review is to identify effective enteral nutritional regimens targeting protein and calorie delivery for the critically ill obese patient on morbidity and mortality. More specifically, the review question is: In the critically ill obese patient, what is the optimal enteral protein and calorie target that improves mortality and morbidity? INCLUSION CRITERIA Types of participants This review will consider studies that include critically ill obese adult patients receiving enteral nutritional support at any stage during their Intensive Care Unit admission for a time period of greater than 72 hours. Studies eligible for retrieval will include intensive care patients in intensive care units or alternatively using a population of patients in which greater than or equal to 50% of trial participants required mechanical ventilation. In attempting to limit the search to studies involving critically ill patients in this way, it is acknowledged that there are differing criteria that determine Intensive Care Unit admission between countries determined in part by resources, in part by cultural differences and in part by the model of intensive care that predominates (closed versus open Intensive Care Units). This is, however, a universal conundrum of critical care research in which there is often heterogeneity in admission diagnosis, severity of disease, metabolic derangement and therapeutic interventions, and which has been recognized in other publications. Critically ill populations comprising both elective and emergency Intensive Care Unit admissions will be included, as will critically ill populations with a medical or surgical TRUNCATED AT 250 WORDS

Catecholamine-Based Treatment in AD Patients: Expectations and Delusions.

In Alzheimer disease, the gap between excellence of diagnostics and efficacy of therapy is wide. Despite sophisticated imaging and biochemical markers, the efficacy of available therapeutic options is limited. Here we examine the possibility that assessment of endogenous catecholamine levels in cerebrospinal fluid (CSF) may fuel new therapeutic strategies. In reviewing the available literature, we consider the effects of levodopa, monoamine oxidase inhibitors, and noradrenaline (NE) modulators, showing disparate results. We present a preliminary assessment of CSF concentrations of dopamine (DA) and NE, determined by HPLC, in a small dementia cohort of either Alzheimer’s disease (AD) or frontotemporal dementia patients, compared to control subjects. Our data reveal detectable levels of DA, NE in CSF, though we found no significant alterations in the dementia population as a whole. AD patients exhibit a small impairment of the DA axis and a larger increase of NE concentration, likely to represent a compensatory mechanism. While waiting for preventive strategies, a pragmatic approach to AD may re-evaluate catecholamine modulation, possibly stratified to dementia subtypes, as part of the therapeutic armamentarium.

The suppression of endogenous adrenalin in the prolongation of ketamine anesthesia

This study investigated whether or not the anesthetic effect of ketamine in rats is dependent on adrenal gland hormones. The study was performed on two main rat groups, intact and adrenalectomized. Rat were divided into subgroups and given appropriate doses of ketamine, metyrapone or metyrosine. Durations of anesthesia in the groups were then recorded. Endogenous catecholamine levels were measured in samples taken from peripheral blood. This experimental results showed that ketamine did not induce anesthesia in intact rats at doses of 15 or 30mg/kg, and that at 60mg/kg anesthesia was established for only 11min. However, ketamine induced significant anesthesia even at a dose of 30mg/kg in animals in which production of endogenous catecholamine (adrenalin, noradrenalin dopamine) was inhibited with metyrosine at a level of 45–47%. Ketamine at 60mg/kg in animals in which endogenous catecholamine was inhibited at a level of 45–47% established anesthesia for 47.6min. However, ketamine at 30 and 60mg/kg induced longer anesthesia in adrenalectomized rats with higher noradrenalin and dopamine levels but suppressed adrenalin production. Adrenalin plays an important role in the control of duration of ketamine anesthesia, while noradrenalin, dopamine and corticosterone have no such function. If endogenous adrenalin is suppressed, ketamine can even provide sufficient anesthesia at a 2-fold lower dose. This makes it possible for ketamine to be used in lengthy surgical procedures.

Early adrenaline administration does not improve circulatory recovery during resuscitation from severe asphyxia in newborn piglets

Aim of the studyTo investigate the effects of early intravenous adrenaline administration on circulatory recovery, cerebral reoxygenation, and plasma catecholamine concentrations, after severe asphyxia-induced bradycardia and hypotension. MethodsOne-day-old piglets were left in apnoea until heart rate and mean arterial pressure were less than 50min−1 and 25mmHg, respectively. They randomly received adrenaline, 10μgkg−1 (n=16) or placebo (n=15) and were resuscitated with air ventilation and, when needed, closed-chest cardiac massage (CCCM). Eight not asphyxiated animals served as time controls. ResultsCCCM was required in 13 piglets given adrenaline and in 13 given placebo. Time to return of spontaneous circulation was: 72 (66–85)s vs. 77 (64–178)s [median (quartile range)] (p=0.35). Time until cerebral regional oxygen saturation (CrSO2) had increased to 30% was 86 (79–152)s vs. 126 (88–309)s (p=0.30). The two groups did not differ significantly in CrSO2, heart rate, arterial pressure, right common carotid artery blood flow, or number of survivors: 13 vs. 11 animals. Plasma concentration of adrenaline, 2.5min after resuming ventilation, was 498 (268–868)nmoll−1vs. 114 (80–306)nmoll−1 (p=0.01). Corresponding noradrenaline concentrations were 1799 (1058–4182)nmoll−1vs. 1385 (696–3118)nmoll−1 (ns). In the time controls, the concentrations were 0.4 (0.2–0.6)nmoll−1 of adrenaline and 1.8 (1.3–2.4)nmoll−1 of noradrenaline. ConclusionThe high endogenous catecholamine levels, especially those of noradrenaline, may explain why early administered adrenaline did not significantly improve resuscitation outcome.

The impact of beta‐blocker therapy on anemia after traumatic brain injury

An increase in endogenous catecholamine levels after traumatic brain injury (TBI) is well described. Animal studies suggest that postinjury anemia is exacerbated by a persistent hyperadrenergic state. This study aims to determine if beta-blocker (BB) exposure affects anemia after TBI. We reviewed a Level I trauma registry for patients with TBI, examining markers of anemia between patients who received BB with those who did not. A total of 174 patients were exposed to BB (BB+) and 245 were not exposed (BB-). The mean age in the BB+ group was 50 years (vs. 36 years in BB- group, p < 0.001). The mean injury severity score was 33.6 for the BB+ group (vs. 30.8 for BB- group, p = 0.01). While BB+ patients were more likely to receive a transfusion (60.9% vs. 35.1%, p < 0.001), BB+ patients reached their nadir hemoglobin (Hb) at a later day of hospitalization and their rate of decrease in Hb was significantly slower (both p < 0.001). Choosing Hb cutoffs for anemia of both 7 and 10 g/dL, Kaplan-Meier demonstrated a significant delay in time to anemia. This study suggests beta-blockade delays anemia after TBI. Elaboration of this effect may demonstrate an additional benefit of beta-blockade after head injury.

Effects of Animal Positioning on Catecholamine and Vasopressin Levels in Pigs Undergoing Laparoscopy

Background: The aim of this study was to determine the influence of different therapeutic interventions and positions on catecholamine and vasopressin levels in the pneumoperitoneum (PN) in a porcine model. Methods: In 43 pigs, a 14-mm-Hg PN was established and plasma concentrations of epinephrine, norepinephrine and vasopressin were measured in head-up, supine and head-down positions. Additionally, the effects of the following changes were studied: (1) increase in intrathoracic blood volume (ITBV) by means of hydroxyethyl starch infusion; (2) vasodilatation induced by sodium nitroprusside, or (3) selective sympathicolysis induced by esmolol. Again, catecholamines (ELISA) and vasopressin (RIA) were determined. Results: After PN, epinephrine levels did not significantly increase in the head-up position (p = 0.075) and remained also unchanged in the supine or head-down position. Plasma norepinephrine statistically significantly decreased in the head-up position (p = 0.046). Vasopressin concentrations remained unaltered. After increased ITBV, neither catecholamine nor vasopressin concentrations changed in any body position. Application of sodium nitroprusside or esmolol caused no changes. Conclusion: Changes in endogenous catecholamine levels safely prevent cardiocirculatory instability in small pigs. Volume substitution might reduce endocrine responses to PN in the head-up position.

Expression and activation of β-adrenoceptors in the colorectal mucosa of rat and human

The functions of the distal colon are regulated by local and extrinsic neural pathways. In previous studies, we have found that dopamine (DA) and norepinephrine (NE) could evoke colonic ion transport by activating β-adrenoceptors. The present study aims to investigate the segmental differences in expression and activation of β-adrenoceptors in the distal colon in physiological and pathophysiological conditions. Real-time PCR, immunofluorescence, and Western blotting were used to detect the expression of β-adrenoceptors in the rat and human distal colon. Short-circuit current measurements (Isc) were used to assess the role of β-adrenoceptors in ion transport. DA and NE caused greater suppression of baseline Isc in distal colon adjacent to the rectum than in segments further away from the anus. These responses were inhibited by selective antagonists of β₁- and β₂-adrenoceptors, but not β₃-adrenoceptor. The expression levels of β₁- and β₂-adrenoceptors in colonic mucosa were higher in colorectum than the regions away from the anus of rats and humans. In wrap-restraint stress (2 h), DA-, NE-induced ΔIsc and the expression of β-adrenoceptors in the colorectum were significantly reduced. However, when endogenous catecholamines were depleted by 6-hydroxydopamine (75 mg kg(-1), i.p., 3 days), DA-, NE-induced ΔIsc as well as the expression of β-adrenoceptors were significantly enhanced in the rat colorectum but not in more proximal regions of the distal colon. β₁- and β₂-adrenoceptors are predominantly expressed in the colorectal mucosa. Perturbation of endogenous catecholamine levels influences the expression and activation of β-adrenoceptors in the colorectal region.

Evidence for inhibition of leptin secretion by catecholamines in man.

The regulation of leptin secretion is complex and not entirely understood in humans. Insulin has been shown to stimulate leptin secretion in humans, whereas in vitro data suggest that catecholamines inhibit leptin secretion. The present studies were therefore undertaken to examine the leptin response to hyperinsulinemia in the presence and absence of elevated plasma levels of endogenous catecholamines in humans. Leptin concentrations were determined during both a euglycemic and hypoglycemic hyperinsulinemic clamp study in 10 normal and 10 type I diabetic subjects. Serum leptin increased during the hyperinsulinemic euglycemic clamp in normal (from 6.1 +/- 0.9 to 7.2 +/- 1.1 ng/dl, p = 0.003) and diabetic subjects (from 6.2 +/- 1.4 to 7.8 +/- 1.8 ng/dl, p = 0.001). During hyperinsulinemic hypoglycemia leptin concentrations increased significantly in type 1 diabetic patients (from 5.6 +/- 1.1 to 7.6 +/- 1.7 ng/dl, p = 0.003) but remained unaltered in normals (from 5.5 +/- 0.7 to 5.7 +/- 0.9 ng/dl, p = 0.7). During hypoglycemia in all subjects the increase in leptin was negatively correlated with the increase in epinephrine (r = 0.60, p = 0.005) and positively with the decrease in free fatty acids (r = 0.71, p = 0.003). In conclusion our results indicate that catecholamines play a suppressive role in the regulation of leptin secretion.

Endogenous catecholamine levels and function of the systemic right ventricle following atrial switch

Background As a result of successful surgery there is a large cohort of young adults with systemic right ventricles, suffering from progressive right ventricular dysfunction. Beta-blockers are successfully used in left ventricular failure. We assessed catecholamine levels and related it to cardiac function late following atrial switch, to provide the pathophysiologic basis for pharmacotherapy in patients with systemic right ventricles. Methods It was a prospective study of 23 consecutive adult patients with the complete transposition of the great arteries, following atrial switch. Epinephrine and norepinephrine concentrations were measured with high performance liquid chromatography. Results Mean ± SD epinephrine and norepinephrine levels were 54.5 ± 29.0 pg/mL and 389.6 ± 134.2 pg/mL, respectively. In multivariate stepwise regression models, sex ( B = − 0.455, 95% CI for B of − 0.887 to − 0.023, P = 0.04), age ( B = − 1.328, 95% CI for B of − 2.402 to − 0.254, P = 0.018), and cardiothoracic ratio ( B = 2.302, 95% CI for B of 0.120–4.484, P = 0.04) were significant predictors of epinephrine levels. Diastolic right ventricular cavity area ( B = 0.024, 95% CI for B of 0.009–0.038, P = 0.003) was a significant predictor of norepinephrine levels. Significantly higher levels of epinephrine were observed in patients with vs without left ventricular tract obstruction (88.0 ± 15.5 vs 47.4 ± 26.2 pg/mL, P = 0.008). Conclusions We have demonstrated a significant correlation between right ventricular enlargement and epinephrine as well as norepinephrine levels. Elevated catecholamine levels were observed in patients with left ventricular tract obstruction. This supports the use of beta-blockers in the selected patients with systemic right ventricles following atrial switch.

Vasopressin in paediatric practice

Arginine vasopressin (AVP) is a nine amino acid peptide hormone, which is synthesized in the hypothalamus as a precursor, transported down the portal system and stored in the posterior pituitary gland. It is also known as argipressin or antidiuretic hormone (ADH) and it is closely related in structure to oxytocin, which is also released from the posterior pituitary. Physiologically, it acts though the kidney with several other hormones to conserve solute-free water, but in hypovolemic states its potent arterial and venoconstrictor properties act to preserve blood pressure. Vasopressin has been used for many years in the treatment of diabetes insipidus and in control of bleeding esophageal varices (utilizing its potent vasoconstrictor effect on the slanchnic circulation), but its role as a pressor agent in the context of resuscitation, septic shock and pediatric cardiac surgery has only emerged in the last few years. Vasopressin is released physiologically in response to a rise in osmolarity, which is sensed within sensitive receptors in the hypothalamus. A fall in osmolarity below 280 mOsmAEkg will trigger its release (1). It acts via V2 receptors to open aquaporin (water channels) in the collecting tubules thereby increasing central water reabsorption. Reduction in afferent transmission from baroreceptors or cardiopulmonary volume receptors associated with hypovolemia or hypotension will also trigger vasopressin release which then acts via V1a receptors of smooth muscle to produce vasoconstriction of both veins and arteries (2). Similarly, increases in circulating ANG11 act via the hypothalamus to trigger release (3). The vasoconstictive effects are specific to different organ beds with the slanchnic bed being particularly sensitive to the circulating concentrations of vasopressin. In addition, increase in vasopressin activity is associated with increased release of corticotrophin releasing hormone via V1b (V3) receptors within the CNS, an increase in release of FV111, Von Willebrand Factor and enhanced platelet aggregation. The physiological effects on the heart are unclear. In the isolated healthy myocyte AVP produces improved contractility (4) probably by increasing intracellular calcium in myocardial cells through a GTP mechanism (5): The integrated position is less clear: pharmacological doses cause coronary vasoconstriction, while improved inotropic performance in pathological states may occur due both primary myocardial effect of secondary effects because of improved coronary perfusion. Pathologically, vasopressin is known to rise in heart failure and conditions of cardiovascular compromise. There are less data in children: in a study of neonates with congenital heart disease, AVP levels in infants with congestive heart and no outflow tract obstruction was significantly higher than normal controls but those with failure and left ventricular outflow tract obstruction had reduced levels (6). The available data suggest that while vasopressin levels are often raised appropriately in hypotensive states because of a variety of conditions this is not necessarily the case. Small studies have been published documenting vasopressin deficiency in catecholamine resistant hypotension (7,8). Vasopressin became of interest when it was observed that organ donors who had brain death and diabetes insipidus were cardiovascularly more stable with reduced inotrope requirements and better organ preservation. Additionally, it was observed that patients who survived cardiac arrest had higher levels of vasopressin compared to nonsurvivors (9). In contrast, there is a correlation of poorer outcome after cardiopulmonary resuscitation with higher levels of endogenous catecholamines (10). These observations led to initial adult studies which questioned whether the purer vasoPediatric Anesthesia 2008 18: 579–581 doi:10.1111/j.1460-9592.2008.02520.x

Effect of Corticosteroids and Neuropeptides on the Expression of Defensins in Bovine Tracheal Epithelial Cells

Susceptibility to bacterial pneumonia in cattle is enhanced by stressors such as transportation, weaning, and commingling, which trigger a physiologic stress response resulting in elevated levels of endogenous corticosteroids and catecholamines. To determine the effect of neuroendocrine mediators on the expression of innate defense peptides in the lung, bovine tracheal epithelial cells were exposed to dexamethasone, catecholamines, acetylcholine, or substance P, and then beta-defensin expression was quantified using real-time reverse transcription-PCR. Basal expression of tracheal antimicrobial peptide (TAP) mRNA was not affected by any of the mediators tested. However, induction of TAP expression by lipopolysaccharide was significantly inhibited by pretreatment with dexamethasone. Bronchial biopsy specimens from dexamethasone-treated calves had significantly lower expression of TAP and lingual antimicrobial peptide (LAP) mRNA than saline-treated controls following 48 h of treatment. Lipopolysaccharide-elicited neutrophil recruitment was enhanced in the lungs of dexamethasone-treated calves compared to saline-treated controls. These findings indicate that modulation of epithelial antimicrobial peptide expression is one mechanism through which corticosteroids and stress may impair innate pulmonary defenses.