Catecholamine Release Research Articles

When a Multidisciplinary Approach Is Life-Saving: A Case Report of Cardiogenic Shock Induced by a Large Pheochromocytoma.

Background: Pheochromocytoma is known for its instantaneous presentation, especially in the younger population. Hemodynamic instability may be the cause of severe complications and impede patients’ ability to undergo surgical treatment. These tumours are surgically difficult to treat due to the risk of catecholamine release during their manipulations, and when they are large, the tumour size represents an additional challenge. In our report, cardiogenic shock developed due to increases in systemic vascular resistance, and the lesion’s size induced surgeons to perform open surgery. Case presentation: A 46-year-old female patient was admitted to our intensive care unit with hypertension and later cardiogenic shock. Systolic dysfunction was noted, along with severely increased systemic vascular resistance. A CT scan showed a left-sided 8.5 cm adrenal mass, which was confirmed as pheochromocytoma using meta-iodobenzylguanidine scintigraphy. Anaesthesiologists and the surgical team planned an effective strategy of treatment. Given the lesion’s size and its apparent invasion of the neighbouring organs, open adrenalectomy (after prolonged hemodynamic stabilisation) was considered safer. The surgery was successful, and the patient remains free from disease two years after the initial event. Conclusions: Large pheochromocytoma can be safely and effectively treated with open surgery by experienced hands but only by seeking to reach hemodynamic stabilisation and minimising the release of catecholamine before and during surgery.

Comparison of Hemodynamic Response to Laryngoscopy Using Miller and McCoy Blade.

Background: The most commonly used equipment to aid endotracheal intubation is a laryngoscope, and the procedure performed is known as laryngoscopy, which leads to profound cardiovascular effects. The process of laryngoscopy causes the release of catecholamines, thereby leading to marked pressor responses and tachycardia. The process of laryngoscopy can be made easier by the use of various types of laryngoscopic blades. The McCoy blade is a modification of the standard Macintosh blade that incorporates a hinged tip blade. It allows elevation of the epiglottis while decreasing overall laryngeal movement. A Miller blade is a straight blade with a slight upward curve near the tip. It is found that the force exerted, head extension, and cervical spine movement are less with the Miller blade. This study was undertaken to compare changes in haemodynamic parameters before, during, and after laryngoscopy using these two blades.Materials and methods: Following institutional ethical committee approval and obtaining informed written consent, 100 patients of American Society of Anesthesiologists (ASA) grades I and II in the age group of 18-45 years of either sex undergoing elective surgeries under general anaesthesia were included in the study. The patients were randomly allocated into two groups of 50 patients each. Group Mc - laryngoscopy was performed using a no. 3 McCoy blade. Group Ml - laryngoscopy was performed using a no. 2 Miller blade. The laryngoscopic view was compared using Cormack and Lehane grading. Haemodynamic parameters before, during, and after laryngoscopy were recorded.Results: Hemodynamic parameters including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were increased in both the groups but were statistically and clinically significant in the Miller group with p≤0.001.Conclusion: McCoy blade is associated with a significantly more stable hemodynamic response to laryngoscopy in comparison with the Miller blade.

Is there a difference in symptoms, catecholamine release and tumor size in pheochromocytomas diagnosed due to initially symptoms or incidenthalomas

Is there a difference in symptoms, catecholamine release and tumor size in pheochromocytomas diagnosed due to initially symptoms or incidenthalomas

Interventional therapies for management of hip fracture pain peri-operatively: A review article

Background Hip fracture is a common reason for elderly admission to hospital and majority of patients will require a hip fixation surgery. Pain originating from a hip fracture is usually severe and the need to improve comfort is paramount, especially before the hip fixation surgery because severe pain results in unnecessary stress response such as catecholamines release, tachycardia and hypertension. This worsens outcomes, increases risk of complications such as myocardial ischaemia, strokes, pulmonary embolus or deep vein thrombosis. Multimodal systemic analgesia has been shown to be effective in reducing pain in hip fractures but the associated side effects and contraindications have accelerated the adoption of nerve blocks in the peri-operative management of hip fracture patients. 1 As a result, this has been increasingly recognised as a important component of the hip fracture pathway (as part of a multimodal approach for analgesia) and many hospitals have protocols to perform various interventional therapies (various nerve blocks) for newly admitted patients with hip fracture to alleviate pain immediately and potentially provide intra and post-operative analgesia. Objective The aim of this review is to elucidate the various interventional therapies currently available (including pericapsular nerve group (PENG) block which was first described in 2018), their evidence and the pros and cons. Methods We reviewed the latest evidence for femoral nerve block (FNB), 3-in-1 block, lumbar plexus block (LPB), fascia iliaca block (FIB), erector spinae plane block (ESPB) and pericapsular nerve group (PENG) block. Results and conclusion Each block has its pros and cons, as discussed in this review article. The procedurist should deliberate these considerations before deciding which block is most appropriate.

The Serotonin Transporter Modulates the Kinetics and Quantal Size of Vesicular Fusion Events in Sympathoadrenal Chromaffin Cells

The antidepressant‐sensitive serotonin transporter (SERT) is a key regulator of serotonin (5‐HT) signaling and availability in the CNS. The robust expression of SERT in adrenal chromaffin cells (ACCs), which comprise the neuroendocrine arm of the sympathetic nervous system, is less well understood. ACCs synthesize and secrete catecholamines (epinephrine, norepinephrine) which mediate the physiological response to stress. They do not synthesize 5‐HT, but do accumulate small amounts through SERT‐mediated uptake (5‐HT content is <0.15% of the epinephrine content). We hypothesized that the chromaffin cells utilize this 5‐HT for autocrine / paracrine control of the sympathoadrenal stress response. Consistent with this hypothesis, we previously reported that 5‐HT1A receptors inhibit catecholamine secretion by reducing the number of secretory vesicles that fuse with the plasma. The objective of the current study was to investigate an additional, receptor‐independent mechanism by which SERT controls adrenal catecholamine secretion.We used carbon fiber amperometry to analyze catecholamine secretion from ACCs that were isolated from either wild type mice, global SERT‐knockout mice (SERT‐/‐), or sympathoadrenal system‐specific SERT knockout mice (SERTΔTH). Transmitter release from individual vesicle fusion events can be resolved as amperometric spikes. There was no difference in the number or time‐course of amperometric spikes evoked by 30mM KCl. The charge of the spikes is directly proportional to the amount of transmitter released by a single vesicle (i.e. quantal size). Spike charge was significantly smaller (~35%) and spike duration (half‐width) was significantly shorter in SERT‐knockout cells compared to matched controls. This was surprising given that HPLC analysis revealed no change in the catecholamine content of adrenal glands isolated from knockout mice compared to wild‐type controls; the 5‐HT content was significantly reduced but this accounted for <0.15% of the total monoamine content. Changes in calcium entry can modulate the quantal size of catecholamine release in ACCs, but patch‐clamp recording revealed there was no significant difference in voltage‐gated calcium channel currents in SERT knockout cells and ratiometric calcium imaging found no difference in KCl‐evoked calcium entry. The decrease in quantal size was mimicked in wild‐type cells by treating for >24 hours with escitalopram (an SSRI antidepressant which blocks SERT), or by depleting extracellular 5‐HT from the culture medium for >24 hours (use of dialyzed serum in the culture media). In contrast, acute (minutes) or short‐term (<6‐8 hrs) treatment with escitalopram or 5‐HT depletion had no effect. Adrenal chromaffin cells lack the rate limiting enzyme for 5‐HT synthesis (tryptophan hydroxylase), but if the product of this enzyme (5‐hydroxytryptophan; 5‐HTP) is provided it can be converted into 5‐HT. Treating ACCs with 5‐HTP for 1‐3 hrs had no effect but 24 hr treatment rescued the reduced spike charge seen in SERT knockout cells. Together, our data suggest that, following SERT‐mediated uptake, intracellular 5‐HT modulates the kinetics and thus fraction of secretory vesicle content that is released during a fusion event.

Mental Stress Pressor Response and Post‐Stress Aortic Wave Reflection

Reactivity to mental stress has been linked to cardiovascular risk, and is shown to negatively influence aortic wave reflection for up to an hour after acute mental arithmetic. It has been postulated that sympathetic catecholamine release during the stressful task drives the sustained elevation in wave reflection. In the present study we sought to determine how muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) reactivity influence post mental stress aortic augmentation index (AIx). Twenty‐seven volunteers (25±1 years) with resting blood pressure ≥120/80 mmHg participated in the present study. Baseline pulse wave analysis and pulse wave velocity recordings were assessed on participants after 10 minutes of supine rest. Participants were then instrumented for measurements of MSNA (microneurography), beat‐to‐beat blood pressure (finger plethysmography), and heart rate (3‐lead ECG). Subsequently MSNA, blood pressure, and heart rate were measured during a 5‐minute baseline, 5‐minute mental stress task (serial subtraction), and 5‐minute recovery. Finally, aortic wave reflection (i.e. AIx) was reassessed 10 minutes after completion of mental stress. Statistical analyses included paired t‐tests to compare MSNA, MAP, heart rate (HR), and perceived stress during baseline and mental stress. We used standard multiple regression with change in AIx as the dependent variable and changes in MSNA, MAP, and perceived stress as the independent variables. Means were considered significantly different when p<0.05. The mental stress task significantly increased HR (Δ15±2 beats/minute), MAP (Δ14±1 mmHg), and perceived stress (Δ1.9±0.1 a.u.), while MSNA was not significantly increased. There was however a range of changes in MSNA from ‐13 to +20 bursts/minute. The change in MAP during mental stress was a significant predictor (ꞵ=0.47; p=0.03) of the change in AIx (post‐stress vs. baseline). Changes in MSNA and perceived stress were not predictors of mental stress‐related changes in AIx. Our results indicate that the aortic wave reflection responses to mental stress appear to be linked to the pressor response, but not sympathetic or perceived stress responses. This is novel preliminary data that suggests there may not be a direct link between sympathetic activation and aortic wave reflection following cognitive stress.

La Esclerosis lateral amiotrófica no es solo una enfermedad de la motoneurona: impacto del eje simpatoadrenal

Amyotrophic lateral sclerosis (ALS), an adult onset, fatal neurodegenerative disease, has as a cardinal pathogenic feature the selective death of motor neurons (MNs) at the cortex, brainstem, and spinal cord. In this review we focus on four aspects: (i) the hypothesis of disease propagation through the cerebrospinal fluid (CSF); (ii) the distortion of the exocytotic release of neurotransmitters at the sympathoadrenal axis; (iii) the ultrastructural and functional alterations of mitochondria from adrenal medullary chromaffin cells (CCs); and (iv) the purinergic P2X7 receptor (P2X7R) as a potential target for neuroprotection. Concerning disease propagation from one to another area of the central nervous system (CNS), the pattern of clinical progression suggests that the disease spreads centrifugally. This indicates that a kind of toxin agent may be released and propagated through the CSF. In our laboratory we found that CSF from ALS patients exerted toxic effects on cultured cortical MNs. In CCs, we found deep distortions of the exocytotic kinetics and the exocytotic fusion pore in the process of catecholamine release, in the SOD1G93A mouse model of ALS. Furthermore, we found that these alterations could be related to the accumulation of mutated SOD1 into mitochondria; this resulted in mitochondrial depolarization, excess production of reactive oxygen species and deficiency in oxidative phosphorylation. Finally, we discuss recent data on the potential therapeutic effect of compound JNJ-47965567, a blocker of P2X7Rs known to be central-stage in neuroinflammation. Upon its chronic administration to SOD1G93A, we found that the compound delayed disease onset but only in females mice. In conclusion, why MN selectively die in ALS disease, remains a mystery; On the other hand, it seems that other cell types are also affected, particularly at the sympathoadrenal axis. As disease pathogenesis remains obscure, the search of therapeutic targets to slow disease progression in ALS, remains puzzling.

Vagus Nerve Stimulation as a Potential Therapy in Early Alzheimer's Disease: A Review.

Cognitive dysfunction in Alzheimer’s disease (AD) is caused by disturbances in neuronal circuits of the brain underpinned by synapse loss, neuronal dysfunction and neuronal death. Amyloid beta and tau protein cause these pathological changes and enhance neuroinflammation, which in turn modifies disease progression and severity. Vagal nerve stimulation (VNS), via activation of the locus coeruleus (LC), results in the release of catecholamines in the hippocampus and neocortex, which can enhance synaptic plasticity and reduce inflammatory signalling. Vagal nerve stimulation has shown promise to enhance cognitive ability in animal models. Research in rodents has shown that VNS can have positive effects on basal synaptic function and synaptic plasticity, tune inflammatory signalling, and limit the accumulation of amyloid plaques. Research in humans with invasive and non-invasive VNS devices has shown promise for the modulation of cognition. However, the direct stimulation of the vagus nerve afforded with the invasive procedure carries surgical risks. In contrast, non-invasive VNS has the potential to be a broadly available therapy to manage cognitive symptoms in early AD, however, the magnitude and specificity of its effects remains to be elucidated, and the non-inferiority of the effects of non-invasive VNS as compared with invasive VNS still needs to be established. Ongoing clinical trials with healthy individuals and patients with early AD will provide valuable information to clarify the potential benefits of non-invasive VNS in cognition and AD. Whether invasive or non-invasive VNS can produce a significant improvement on memory function and whether its effects can modify the progression of AD will require further investigation.

Neurogenic stunned myocardium resulting from surgical brainstem handling during resection of paediatric recurrent medulloblastoma—a possible brain heart interaction

Neurogenic stunned myocardium (NSM) is characterised by an acute onset cardiac dysfunction following an acute neurological insult which mimics acute coronary syndrome. A 12-year-old male child was admitted to the neuro-intensive care unit (NICU) following midline suboccipital craniotomy and resection of recurrent medulloblastoma. Postoperatively, in NICU, he developed tachycardia and hypotension, which was unresponsive to fluid challenge requiring norepinephrine infusion. Intraoperatively, during tumour resection from the dorsal medulla, episodes of hypertension and bradycardia were observed. Intraoperative blood loss was adequately managed with a stable hemodynamic profile without postoperative anaemia. An electrocardiogram showed sinus tachycardia with T wave inversion, and blood investigation revealed elevated cardiac troponin T levels. Point of care ultrasound (POCUS) of heart and lung showed features of NSM. Infusion dobutamine was added to achieve a target mean arterial pressure of 65mm Hg with concomitant furosemide infusion and fluid restriction. Daily POCUS assessment of cardiac contractility and volume status was done. The patient was weaned from vasoactive drugs and ventilator following improvement of cardiac function and was discharged from NICU after 17days. NSM results from the excessive release of catecholamines following stimulation of trigger zones in the brain. To date, a handful of cases of pediatric NSM following primary brain tumour are reported where hydrocephalus resulted in trigger zone activation. In this presented case, direct brain stem stimulation during tumour resection might have triggered NSM. Irrespective of the cause, timely diagnosis and execution of supportive management in our patient resulted in a positive outcome.

Diencephalic storm in trauma patients: Is it really that rare

Introduction: Diencephalic storm is characterized by extreme episodic catecholamine release in the presence of a stressor and it is usually refractory to standard antihypertensives. The treatment of choice during the crisis is propofol and the best preventative measure is to remove the stressor (i.e. ventilator). Case presentation: A 32-year-old male sustained 2nd and 3rd degree burn to 25 percent of the body surface area that included a severe inhalation component. The patient was admitted to the Burn Intensive Care Unit at the Arnold Luterman Regional Burn Center in Mobile, AL. The patient had frequent episodes (3-5 per day) of severe agitation that were accompanied by extreme tachycardia of > 200 beats per minute and hypertension (280/140). The inciting event was often endotracheal suctioning, but less noxious stimulation also resulted in similar episodes. During these episodes, the patient had significantly elevated catecholamine levels that improved after extubation. The patient’s symptoms were refractor to standard antihypertensives but immediately resolved when given propofol. Further episodes of the diencephalic storm were treated successfully with propofol. Once the patient was removed from mechanical ventilation, there were no further episodes. Conclusion: Diencephalic Storm may be difficult to diagnose due to a lack of familiarity with this rare entity. Any patient with severe agitation combined with the effects of episodic large catecholamine surges should be considered to have Diencephalic Storm. The standard immediate treatment is propofol due to the lack of responsiveness of standard antihypertensives and the removal of the stressor.

Estrogen receptors observed at extranuclear neuronal sites and in glia in the nucleus accumbens core and shell of the female rat: Evidence for localization to catecholaminergic and GABAergic neurons.

Estrogens affect dopamine-dependent diseases/behavior and have rapid effects on dopamine release and receptor availability in the nucleus accumbens (NAc). Low levels of nuclear estrogen receptor (ER) α and ERβ are seen in the NAc, which cannot account for the rapid effects of estrogens in this region. G-protein coupled ER 1 (GPER1) is observed at low levels in the NAc shell, which also likely does not account for the array of estrogens' effects in this region. Prior studies demonstrated membrane-associated ERs in the dorsal striatum; these experiments extend those findings to the NAc core and shell. Single- and dual-immunolabeling electron microscopy determined whether ERα, ERβ, and GPER1 are at extranuclear sites in the NAc core and shell and whether ERα and GPER1 were localized to catecholaminergic or γ-aminobutyric acid-ergic (GABAergic) neurons. All three ERs are observed, almost exclusively, at extranuclear sites in the NAc, and similarly distributed in the core and shell. ERα, ERβ, and GPER1 are primarily in axons and axon terminals suggesting that estrogens affect transmission in the NAc via presynaptic mechanisms. About 10% of these receptors are found on glia. A small proportion of ERα and GPER1 are localized to catecholaminergic terminals, suggesting that binding at these ERs alters release of catecholamines, including dopamine. A larger proportion of ERα and GPER1 are localized to GABAergic dendrites and terminals, suggesting that estrogens alter GABAergic transmission to indirectly affect dopamine transmission in the NAc. Thus, the localization of ERs could account for the rapid effects of estrogen in the NAc.

Comparison of high dose fentanyl, magnesium and lidocaine for effective and consistent attenuation of hemodynamic responses during laryngoscopy and intubation

Background & objective: Laryngoscopy and endotracheal intubation provoke stress response with consequent hemodynamic instability. Fentanyl is a short acting potent opioid commonly used to control stress response. Magnesium sulphate can attenuate stress response through inhibiting catecholamines release. Systemic administration of lidocaine helps in blocking stress response. This study aimed to compare the effectiveness of high dose fentanyl, magnesium, and lidocaine versus conventional anesthesia on consistent attenuation of stress response to laryngoscopy and endotracheal intubation.
 Methods: 160 patients were randomly allocated into one of the 4 study groups. Group C: received fentanyl 2µg/kg, Group F: received fentanyl 4 µg/kg, Group M: received magnesium sulphate 30mg/kg combined with fentanyl 2µg/kg and Group L: received lidocaine 1.5 mg/kg combined with fentanyl 2 µg/kg. Outcome measures included heart rate (HR) values and mean arterial blood pressure (MAP) values during endotracheal intubation and over the following 5 min in addition to coughing and lacrimation during intubation.
 Results: HR in group C and group L increased compared to baseline readings following intubation and at 1,3,5 min and was statistically significant for group C but comparable for group L. In group F and group M, HR decreased significantly compared to baseline following intubation and the rest of the times studied. MAP in group C and L were maintained for the period of 5 min following intubation whereas group F and L showed a statistically significant reduction in their MAP values compared to baseline readings.
 Conclusion: High dose fentanyl, fentanyl-magnesium combination, and fentanyl- lidocaine combination can attenuate stress response to laryngoscopy and endotracheal intubation when compared to conventional anesthesia. Furthermore, using high dose fentanyl and fentanyl-Magnesium combination results in consistent attenuation of the response.
 Abbreviations: HR – heart rate; MAP – mean arterial blood pressure; PPV - positive pressure ventilation
 Key words: Fentanyl; Magnesium sulphate; Lidocaine; Hemodynamics; Intubation
 Trial registration: This trial was prospectively registered at Clinical Trials.gov on 3 September 2020 with registration number NCT04544163. https://clinicaltrials.gov/ct2/show/NCT04544163
 Citation: Elsabeeny WY, Shehab NN. The role of high dose fentanyl, magnesium and lidocaine for effective and consistent attenuation of hemodynamic responses during laryngoscopy and intubation. Anaesth. pain intensive care 2022;26(3):352-359. DOI: 10.35975/apic.v26i2.1910
 Received: July 05, 2021; Reviewed: March 03, 2022; Accepted: April 22, 2022

Aprocitentan and the endothelin system in resistant hypertension.

Endothelin has emerged as a target for therapeutic intervention in systemic hypertension. As a vasoconstrictor, comitogenic agent, linking pulse pressure and vascular remodeling, and mediator of aldosterone and catecholamine release, endothelin is a key player in hypertension and end-organ damage. In 10%-20% of the hypertensive population, the high blood pressure is resistant to administration of antihypertensive drugs of different classes in combination. Because endothelin is not targeted by the current antihypertensive drugs, this may suggest that this resistance is due, in part at least, to a dependence on endothelin. This hypothesis is supported by the observation that this form of hypertension is often salt-sensitive, and that the endothelin system is stimulated by salt. In addition, the endothelin system is activated in subjects at risk of developing resistant hypertension, such as African Americans or patients with obesity or obstructive sleep apnea. Aprocitentan is an investigational, novel, potent, dual endothelin receptor antagonist (ERA) currently in phase 3 development for the treatment of difficult-to-treat hypertension. This article discusses the research that underpinned the discovery of this ERA and the choice of its first clinical indication for patients with forms of hypertension that cannot be well controlled with classical antihypertensive drugs.

Gambierol Blocks a K+ Current Fraction without Affecting Catecholamine Release in Rat Fetal Adrenomedullary Cultured Chromaffin Cells.

Gambierol inhibits voltage-gated K+ (KV) channels in various excitable and non-excitable cells. The purpose of this work was to study the effects of gambierol on single rat fetal (F19–F20) adrenomedullary cultured chromaffin cells. These excitable cells have different types of KV channels and release catecholamines. Perforated whole-cell voltage-clamp recordings revealed that gambierol (100 nM) blocked only a fraction of the total outward K+ current and slowed the kinetics of K+ current activation. The use of selective channel blockers disclosed that gambierol did not affect calcium-activated K+ (KCa) and ATP-sensitive K+ (KATP) channels. The gambierol concentration necessary to inhibit 50% of the K+ current-component sensitive to the polyether (IC50) was 5.8 nM. Simultaneous whole-cell current-clamp and single-cell amperometry recordings revealed that gambierol did not modify the membrane potential following 11s depolarizing current-steps, in both quiescent and active cells displaying repetitive firing of action potentials, and it did not increase the number of exocytotic catecholamine release events, with respect to controls. The subsequent addition of apamin and iberiotoxin, which selectively block the KCa channels, both depolarized the membrane and enhanced by 2.7 and 3.5-fold the exocytotic event frequency in quiescent and active cells, respectively. These results highlight the important modulatory role played by KCa channels in the control of exocytosis from fetal (F19–F20) adrenomedullary chromaffin cells.

Inflammation and Oxidative Stress as Common Mechanisms of Pulmonary, Autonomic and Musculoskeletal Dysfunction after Spinal Cord Injury.

Simple SummaryWhen a spinal cord injury occurs, the neurons that regulate our voluntary movements, those involved in environment and somatic perception and those that regulate vegetative functions are affected. Once neuronal damage is established, the cells of other tissues are also affected in their functions, altering the interaction between organs and altering the proper functioning of the organism. Multiple studies in animal models, as well as in humans, have recognized as factors involved in organ damage the imbalance between the formation of highly reactive molecules called pro-oxidants and defensive mechanisms called antioxidants. Closely associated with this phenomenon, the inflammatory response is also pathologically activated. In this narrative review, we have analyzed the information involving these pathological processes at the level of the lung, the autonomic nervous system and the skeletal musculature after spinal cord injury. Knowing the abnormal functioning mechanisms that occur after a spinal cord injury not only offers a better understanding of the organic events but also offers future possibilities for therapeutic interventions that may benefit the thousands of patients suffering this pathology.One of the etiopathogenic factors frequently associated with generalized organ damage after spinal cord injury corresponds to the imbalance of the redox state and inflammation, particularly of the respiratory, autonomic and musculoskeletal systems. Our goal in this review was to gain a better understanding of this phenomenon by reviewing both animal and human studies. At the respiratory level, the presence of tissue damage is notable in situations that require increased ventilation due to lower thoracic distensibility and alveolar inflammation caused by higher levels of leptin as a result of increased fatty tissue. Increased airway reactivity, due to loss of sympathetic innervation, and levels of nitric oxide in exhaled air that are similar to those seen in asthmatic patients have also been reported. In addition, the loss of autonomic control efficiency leads to an uncontrolled release of catecholamines and glucocorticoids that induce immunosuppression, as well as a predisposition to autoimmune reactions. Simultaneously, blood pressure regulation is altered with vascular damage and atherogenesis associated with oxidative damage. At the muscular level, chronically elevated levels of prooxidants and lipoperoxidation associated with myofibrillar atrophy are described, with no reduction or reversibility of this process through antioxidant supplementation.

Thrombotic Thrombocytopenic Purpura (ADAMTS13 [a Disintegrin and Metalloproteinase With a Thrombospondin Type 1 Motif, Member 13] Deficiency) as Cause of Recurrent Multiterritory Ischemic Strokes.

Thrombotic Thrombocytopenic Purpura (ADAMTS13 [a Disintegrin and Metalloproteinase With a Thrombospondin Type 1 Motif, Member 13] Deficiency) as Cause of Recurrent Multiterritory Ischemic Strokes.

Alterations of the Sympathoadrenal Axis Related to the Development of Alzheimer's Disease in the 3xTg Mouse Model.

Simple SummaryAlzheimer’s disease (AD), the most common form of dementia, is becoming a global health problem and public health priority. In the advanced stages of AD, besides the initial cognitive symptoms, behavioral problems, particularly agitation and aggressiveness, become prevalent in AD patients. These non-cognitive symptoms could be related to alterations in the regulatory mechanism of the sympathetic nervous system. In this study, we used chromaffin cells (CCs) isolated from the adrenal gland of 3xTg (an AD mouse model) mice to characterize potential alterations in the regulation of the responses to stress mediated by the secretion of catecholamines. We compared these regulatory mechanisms in mice at two different ages: in 2-month-old mice, where no AD symptoms were observed, and in mice over 12 months of age, when AD-related cognitive impairment related was fully established. We found that the modulation of neurotransmitter release was stronger in CCs isolated from the adrenal medulla of 3xTg mice older than 12 months of age, an effect likely related to disease progression as it was not observed in CCs from age-matched wild-type (WT) mice. This enhanced modulation leads to an increased catecholamine release in response to stressful situations, which may explain the non-cognitive behavioral problems found in AD patients.Alzheimer’s disease (AD), the most common form of dementia, is becoming a global health problem and public health priority. In the advanced stages of AD, besides the initial cognitive symptoms, behavioral problems, particularly agitation and aggressiveness, become prevalent in AD patients. These non-cognitive symptoms could be related to a noradrenergic overactivation. In this study, we used chromaffin cells (CCs) isolated from the adrenal gland of 3xTg AD model mice to characterize potential alterations in the autocrine-paracrine modulation of voltage-dependent calcium channels (VDCCs), which in turn serve to regulate the release of catecholamines. We used mice at the presymptomatic stage (2 months) and mice over 12 months of age, when AD-related cognitive impairment was fully established. We found that the modulation of inward currents through VDCCs induced by extracellular ATP was stronger in CCs isolated from the adrenal medulla of 3xTg mice older than 12 months of age, an effect likely related to disease progression as it was not observed in CCs from age-matched WT mice. This enhanced modulation leads to increased catecholamine release in response to stressful situations, which may explain the non-cognitive behavioral problems found in AD patients.

Perioperative Supplemental Oxygen and Plasma Catecholamine Concentrations after Major Abdominal Surgery-Secondary Analysis of a Randomized Clinical Trial.

Perioperative stress is associated with increased sympathetic activity that leads to increases in heart rate and blood pressure, which are associated with the development of perioperative myocardial ischemia. In healthy volunteers, it was shown that the administration of supplemental oxygen attenuated sympathetic nerve activity and subsequently led to lower plasma catecholamine concentrations. We therefore tested the hypothesis that perioperative supplemental oxygen attenuates sympathetic nerve in patients at risk for cardiovascular complications undergoing major abdominal surgery. We randomly assigned 81 patients to receive either 80% or 30% inspired oxygen concentration throughout surgery and the first two postoperative hours. We assessed noradrenaline, adrenaline, and dopamine plasma concentrations before the induction of anesthesia, two hours after surgery and on the third postoperative day. There was no significant difference in postoperative noradrenaline (effect estimated: −41.5 ng·L−1, 95%CI −134.3, 51.2; p = 0.38), adrenaline (effect estimated: 11.2 ng·L−1, 95%CI −7.6, 30.1; p = 0.24), and dopamine (effect estimated: −1.61 ng·L−1, 95%CI −7.2, 3.9; p = 0.57) concentrations between both groups. Based on our results, it seems unlikely that supplemental oxygen influences endogenous catecholamine release in the perioperative setting.

Lactato y catecolaminas: respuesta fisiológica en el paciente crítico

Lactate is a highly dynamic metabolite that is produced, under anaerobic conditions, due to hypoxia or ischemia. Under aerobic conditions, it is synthesized by a mechanism driven by the stimulation of the β2 adrenergic receptor, which increases the activity of the sodium-potassium pump, and by a state of accelerated aerobic glycolysis. This metabolite is capable of being exchanged between different producing and consuming cells, ensuring the raw material for energy production.The sympathetic nervous system responds to stress stimuli through the release of catecholamines, which act as hormones and neurotransmitters in various tissues of the body, allowing an increase in metabolism that raises glucose and available oxygen levels.There is a physiological dependence between catecholamine levels and lactate production, predisposing the body to respond effectively to a stressful situation. However, an exacerbated adrenergic response may cause exaggerated effects on sensitive tissues that increase the probability of failure. Based on the knowledge of these mechanisms, therapeutic strategies focused on regulating the sympathetic activity are proposed.

Prevalence and Impact of Atrial Fibrillation on Prognosis in Takotsubo Cardiomyopathy Patients.

The purpose of this review is to describe the impact of atrial fibrillation (AF) on the cardiovascular outcomes and prognosis in patients with Takotsubo Cardiomyopathy (TTC). The pathophysiological basis of TTC is set on the release of catecholamines, occurring post an emotional or stressful event. The cardiovascular system of patients with TTC is affected by the high concentrations of catecholamines, creating the ideal background for the development of AF: inflammation, myocardial stress, and excessive sympathetic activity. AF is considered to be the most frequent arrhythmia in TTC patients and is associated with higher rates of cardiovascular and all-cause mortality. AF is also linked with a worse prognosis concerning the hemodynamic status, cardiac fibrosis, lethal arrhythmias, thromboembolic events, and adverse heart failure associated outcomes. The early diagnosis of AF in these patients plays significant role in the prevention of adverse events, the reversibility of left ventricular function, and the restoration of sinus rhythm.