BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.

• MeSH
• Adrenergic Agents MeSH
• Atherosclerosis * complications   MeSH
• Phenotype MeSH
• Pheochromocytoma * diagnosis   MeSH
• Myocardial Infarction * MeSH
• Cardiomyopathies * MeSH
• Catecholamines MeSH
• Humans MeSH
• Metanephrine MeSH
• Adrenal Gland Neoplasms * pathology   MeSH
• Paraganglioma * complications   MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.

• MeSH
• Child MeSH
• Adult MeSH
• Pheochromocytoma * genetics   therapy   diagnosis   MeSH
• Humans MeSH
• Adrenal Gland Neoplasms * genetics   therapy   diagnosis   MeSH
• Paraganglioma * genetics   therapy   MeSH
• Succinate Dehydrogenase genetics   MeSH
• Germ-Line Mutation genetics   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Takotsubo syndrom je definován jako syndrom akutního srdečního selhání, který se klinicky velmi často projevuje jako akutní koronární syndrom. Charakteristickým klinickým znakem je přechodná dysfunkce levé komory srdeční. Spouštějícími faktory jsou relativně často akutní neurologická onemocnění, a tak se předpokládá, že v patofyziologii hraje významnou roli právě centrální nervová soustava. Tento přehledový článek si klade za cíl představit základní informace o takotsubo syndromu se zaměřením na velmi pravděpodobné patofyziologické mechanismy v ose mozek­-srdce.

Takotsubo syndrome is defined as a syndrome of acute heart failure that is very often manifested clinically as acute coronary syndrome. Transient left ventricular dysfunction is a characteristic clinical feature. Acute neurological diseases are relatively frequently the triggering factors; thus, it is assumed that it is the central nervous system that plays a significant role in the pathophysiology. The review article aims to provide basic information on Takotsubo syndrome with a focus on the very likely pathophysiological mechanisms in the brain-heart axis.

• MeSH
• Central Nervous System * physiopathology   MeSH
• Mental Disorders complications   physiopathology   MeSH
• Catecholamines adverse effects   MeSH
• Humans MeSH
• Stress, Psychological complications   MeSH
• Sympathetic Nervous System physiopathology   MeSH
• Takotsubo Cardiomyopathy * diagnosis   physiopathology   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Shock, Hemorrhagic diagnosis   etiology   MeSH
• Hypotension diagnosis   etiology   classification   MeSH
• Shock, Cardiogenic diagnosis   etiology   MeSH
• Catecholamines pharmacology   therapeutic use   MeSH
• Multiple Organ Failure diagnosis   etiology   MeSH
• Shock * diagnosis   drug therapy   classification   physiopathology   MeSH
• Publication type
• Review MeSH

Human induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells (PBMCs) isolated from two related patients diagnosed with either idiopathic ventricular fibrillation or catecholaminergic polymorphic ventricular tachycardia, carrying an unknown variant in the RYR2 gene, c.14201A>G (p.Y4734C) and one healthy related individual. Reprogramming was done using a commercially available Epi5 Reprogramming Kit. The pluripotency of the iPSC lines was verified by the expression of pluripotency markers and by their capacity to differentiate into all three embryonic germ layers in vitro. These iPSC lines are available for functional analysis and in vitro studies of RYR2 channelopathy.

• MeSH
• Cell Differentiation MeSH
• Cell Line MeSH
• Adult MeSH
• Ventricular Fibrillation * genetics   MeSH
• Induced Pluripotent Stem Cells * metabolism   MeSH
• Polymorphic Catecholaminergic Ventricular Tachycardia MeSH
• Tachycardia, Ventricular * genetics   metabolism   MeSH
• Humans MeSH
• Ryanodine Receptor Calcium Release Channel * genetics   metabolism   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

One element, potassium, can be identified as the connecting link in the research of Czech neurophysiologist Prof. František Vyskočil. It accompanied him from the first student experiments on the frog muscle (Solandt effect) via sodium-potassium pump and quantum and non-quantum release of neurotransmitters (e.g. acetylcholine) to the most appreciated work on the reversible leakage of K+ from brain neurons during the Leao ́s spreading cortical depression, often preceding migraine. He used a wide range of methods at the systemic, cellular and genetic levels. The electrophysiology and biochemistry of nerve-muscle contacts and synapses in the muscles and brain led to a range of interesting findings and discoveries on normal, denervated and hibernating laboratory mammals and in tissue cultures. Among others, he co-discovered the facilitating effects of catecholamines (adrenaline in particular) by end-plate synchronization of individual evoked quanta. This helps to understand the general effectiveness of nerve-muscle performance during actual stress. After the transition of the Czech Republic to capitalism, together with Dr. Josef Zicha from our Institute, he was an avid promoter of scientometry as an objective system of estimating a scientist ́s success in basic research (journal Vesmír, 69: 644-645, 1990 in Czech).

• MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Brain * physiology   metabolism   MeSH
• Neurons * metabolism   physiology   MeSH
• Neurosciences * MeSH
• Anura MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH

Euglykemická ketoacidóza asociovaná se SGLT2 inhibitory, též označovanými jako glifloziny, je vzácný, ale potenciálně fatální syndrom, charakterizovaný metabolickou acidózou s normální nebo jen mírně zvýšenou glykemií, převážně u diabetiků 2. typu. Kromě ketoacidózy se na metabolické acidóze může významně podílet též hyperchloremická acidóza. Relativní hypoglykemie navozená glifloziny a souběžný stresový stav vedou ke snížení hladiny inzulinu a zvýšení hladiny glukagonu, kortizolu a katecholaminů, což stimuluje ketogenezi. Současně glifloziny indukují komplexní renální metabolickou dysfunkci, zejména zhoršují renální eliminaci kyselin a amoniogenezi, což ústí v hyperchloremickou acidózu. U pacientů užívajících glifloziny by při zhoršení stavu měla být včas zkontrolována acidobazická rovnováha a ketonemie. Léčba acidózy spočívá ve vysazení gliflozinu a podávání inzulinu v dávce postačující k potlačení ketogeneze. Vzhledem k riziku acidózy by měly být glifloziny vysazeny nejméně 3 dny před plánovanou operací a navráceny až po stabilizaci stavu a spolehlivé obnově perorálního příjmu. Podobně by měly být glifloziny vysazeny u většiny hospitalizovaných nechirurgických pacientů s rizikovými faktory rozvoje acidózy, jakou jsou infekce, akutní srdeční onemocnění, cévní mozkové příhody, lačnění před vyšetřením či abúzus alkoholu

Euglycemic ketoacidosis associated with SGLT2 inhibitors, also referred to as gliflozins, is a rare but potentially fatal clinical entity characterized by metabolic acidosis with normal or only mildly elevated glycemia, predominantly in patients with type 2 diabetes mellitus. In addition to ketoacidosis, hyperchloremic acidosis may also contribute significantly to metabolic acidosis. Relative hypoglycemia induced by gliflozins and concomitant stress condition lead to decreased insulin level and increased glucagon, cortisol, and catecholamines, which stimulates ketogenesis. At the same time, gliflozins induce complex renal metabolic dysfunction, in particular impaired renal elimination of acids and renal ammoniogenesis, resulting in hyperchloremic acidosis. In patients treated with gliflozins, acid-base balance and ketonemia should be checked in a timely manner when their condition worsens. Treatment of acidosis consists of discontinuation of gliflozin and administration of insulin at a dose sufficient to suppress ketogenesis. Because of the risk of acidosis, gliflozins should be discontinued at least 3 days before elective surgery and resumed only after stabilization and reliable restoration of oral intake. Similarly, gliflozins should be discontinued in most hospitalized nonsurgical patients with risk factors for the development of acidosis, such as in patients with acute infection, acute heart disease, stroke, fasting before examination, or alcohol abuse.

• MeSH
• Diabetes Mellitus * drug therapy   pathology   MeSH
• Diabetic Ketoacidosis * pathology   MeSH
• Sodium-Glucose Transporter 2 Inhibitors pharmacology   adverse effects   therapeutic use   MeSH
• Blood Glucose drug effects   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there is limited data on the outcomes of ICD use in children. OBJECTIVE: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without an ICD. METHODS: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic CPVT patients with and without an ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. RESULTS: The study included 235 patients, 73 with an ICD (31.1%) and 162 without an ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. CONCLUSION: SCD events occurred only in patients without an ICD and mostly in those not on optimal medical therapy. Patients with an ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.

• MeSH
• Defibrillators, Implantable * MeSH
• Child MeSH
• Polymorphic Catecholaminergic Ventricular Tachycardia MeSH
• Tachycardia, Ventricular * therapy   physiopathology   MeSH
• Humans MeSH
• Adolescent MeSH
• Death, Sudden, Cardiac * prevention & control   etiology   MeSH
• Follow-Up Studies MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Ryanodine Receptor Calcium Release Channel genetics   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence has highlighted the importance of tightly regulated monoamine levels for placental functions and fetal development. However, the complexities of synthesis, release, and regulation of catecholamines in the fetoplacental unit have not been fully unraveled. In this study, we investigated the expression of enzymes and transporters involved in synthesis, degradation, and transport of norepinephrine and dopamine in the human placenta and rat fetoplacental unit. Quantitative PCR and Western blot analyses were performed in early-to-late gestation in humans (first trimester vs. term placenta) and mid-to-late gestation in rats (placenta and fetal brain, intestines, liver, lungs, and heart). In addition, we analyzed the gene expression patterns in isolated primary trophoblast cells from the human placenta and placenta-derived cell lines (HRP-1, BeWo, JEG-3). In both human and rat placentas, the study identifies the presence of only PNMT, COMT, and NET at the mRNA and protein levels, with the expression of PNMT and NET showing gestational age dependency. On the other hand, rat fetal tissues consistently express the catecholamine pathway genes, revealing distinct developmental expression patterns. Lastly, we report significant transcriptional profile variations in different placental cell models, emphasizing the importance of careful model selection for catecholamine metabolism/transport studies. Collectively, integrating findings from humans and rats enhances our understanding of the dynamic regulatory mechanisms that underlie catecholamine dynamics during pregnancy. We identified similar patterns in both species across gestation, suggesting conserved molecular mechanisms and potentially shedding light on shared biological processes influencing placental development.

• MeSH
• Dopamine * MeSH
• Catecholamines * MeSH
• Rats MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Norepinephrine MeSH
• Placenta MeSH
• Pregnancy MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Feochromocytóm/paraganglióm (PPGL) je zriedkavý neuroendokrinný nádor z chromafinných buniek sympatikových ganglií. V 90 % prípadov je lokalizovaný v dreni nadobličiek (feochromocytóm), ak je uložený extraadrenálne (cca 10 %), ide o paraganglióm. PPGL sú nádory produkujúce katecholamíny – adrenalín a/alebo noradrenalín, v prípade extraadrenálnych foriem zriedkavo dopamín. Nadprodukcia týchto hormónov sa u väčšiny pacientov prejaví kardiovaskulárnym ochorením, najčastejšie artériovou hypertenziou. U 8 – 11 % pacientov s PPGL dochádza v dôsledku kardiotoxicity katecholamínov k poškodeniu srdca. Katecholamínmi indukované kardiomyopatie (CICMP) predstavujú závažné, až potenciálne fatálne komplikácie PPGL. Klinický obraz je variabilný, od asymptomatických pacientov až po dramatický priebeh s ťažkým srdcovým zlyhávaním s pľúcnym edémom alebo kardiogénnym šokom. Existujú tri formy CICMP asociovaných s PPGL. Akútna, takotsubo-like kardiomyopatia, typická pre adrenalín produkujúce tumory, a dva chronické typy – dilatačná kardiomyopatia a hypertrofická kardiomyopatia, typická pre nádory produkujúce noradrenalín. Včasná diagnostika a adekvátny manažment vedie u väčšiny pacientov k významnej regresii kardiálnych zmien. Kauzálna liečba spočíva v chirurgickom odstránení PPGL. Inoperabilné alebo metastatické formy PPGL majú častejšie recidívy CICMP a významne horšiu prognózu.

Pheochromocytoma/paraganglioma (PPGL) is a rare neuroendocrine tumour arising from chromaffine cells of sympathetic ganglia. 90% of PPGLs are located in adrenal medulla (pheochromocytoma), the rest are extraadrenal paragangliomas. PPGLs produce catecholamines - adrenaline and/or noradrenaline, in case of extraadrenal forms, dopamine may be rarely secreted. An overproduction of these hormones usually manifests by the cardiovascular diseases, mostly with arterial hypertension. In 8-11% of patients, catecholamine excess leads to heart injury. Katecholamine-induced cardiomyopathies (CICMP) are severe, potentially fatal complications of PPGLs. Clinical manifestation may vary, from asymptomatic forms up to severe heart failure with pulmonary edema or cardiogenic shock. Three types of CICMPs associated with PPGL have been identified. Acute, takotsubo-like cardiomyopathy, typical for adrenalin producing tumours, and two types of chronic forms - dilated cardiomyopathy and hypertrophic cardiomyopathy, the last one typical for noradrenalin-secreting PPGLs. Early diagnosis and appropriate management leads to significant improvement in most of the patients. Though receidiving forms have worse prognosis.

• MeSH
• Pheochromocytoma * complications   MeSH
• Cardiomyopathies * etiology   physiopathology   therapy   MeSH
• Catecholamines adverse effects   MeSH
• Humans MeSH
• Heart Failure etiology   physiopathology   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH