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1.
Eur J Anaesthesiol ; 38(10): 1077-1084, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524157

RESUMO

BACKGROUND: Studies comparing phenylephrine and norepinephrine for the treatment of postspinal hypotension in pre-eclamptic patients are limited. OBJECTIVE: To compare bolus doses of phenylephrine and norepinephrine for treating hypotension in pre-eclamptic mothers undergoing caesarean section under spinal anaesthesia. It was hypothesised that norepinephrine and phenylephrine use would be associated with similar neonatal outcome. DESIGN: Randomised controlled study. SETTING: Single centre, tertiary care, university teaching hospital, from December 2018 to March 2020. PATIENTS: A total of 86 women with pre-eclampsia and a singleton pregnancy who developed postspinal hypotension during caesarean section. INTERVENTIONS: Patients received intravenous phenylephrine (50 µg) or norepinephrine (4 µg) for treatment of hypotension, defined as a fall in baseline systolic BP by ≥ 20% or an absolute value < 100 mmHg. MAIN OUTCOME MEASURES: The primary outcome was umbilical artery pH. Secondary outcomes included Apgar scores, the number of hypotensive episodes, vasopressor requirements, the incidence of tachycardia/bradycardia/arrhythmias/hypertension and maternal complications. RESULTS: Umbilical artery pH was not different between the phenylephrine and norepinephrine groups (7.26 ±â€Š0.06 and 7.27 ±â€Š0.06, respectively; P = 0.903). The median [IQR] number of hypotensive episodes was higher in the norepinephrine than the phenylephrine group: 2 [1 to 3] vs 1 [1 to 2], respectively; P = 0.014. Apgar scores, total number of vasopressor boluses required, systolic BP trends and the incidence of maternal complications were comparable in the two groups. Heart rate (HR) values were lower in phenylephrine group (P = 0.026), and one patient in phenylephrine group and none in the norepinephrine group developed bradycardia (HR < 50 bpm), P = 1.000. CONCLUSIONS: In women with pre-eclampsia undergoing caesarean section, bolus doses of phenylephrine (50 µg) and norepinephrine (4 µg) used to treat hypotension after spinal anaesthesia are equally effective with similar neonatal and maternal outcomes. TRIAL REGISTRATION: CTRI/2018/11/016478.


Assuntos
Anestesia Obstétrica , Raquianestesia , Hipotensão , Pré-Eclâmpsia , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Hipotensão/induzido quimicamente , Hipotensão/diagnóstico , Hipotensão/tratamento farmacológico , Recém-Nascido , Infusões Intravenosas , Norepinefrina , Fenilefrina , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Vasoconstritores/uso terapêutico
2.
Semin Respir Crit Care Med ; 42(5): 672-682, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34544184

RESUMO

While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 µmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.


Assuntos
Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Choque Séptico/tratamento farmacológico , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Deficiência de Ácido Ascórbico/fisiopatologia , Ensaios Clínicos como Assunto , Estado Terminal , Relação Dose-Resposta a Droga , Glucocorticoides/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Vasoconstritores/farmacologia , Vitaminas/administração & dosagem , Vitaminas/efeitos adversos
4.
Med Klin Intensivmed Notfmed ; 116(6): 541-553, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34338810

RESUMO

Circulatory shock requires treatment of the underlying pathology in addition to supportive pharmacological therapy that is guided by hemodynamic monitoring. Based on the evaluation of the patient's volume, perfusion and cardiac status, the following therapeutic goals should be achieved: (1) Normalization of the intra- and extravascular fluid volume. (2) Provision of sufficient perfusion pressure and organ perfusion. (3) Optimization of cardiac function including protecting an ischemic and exhausted myocardium from overload. The most important therapeutic substances are balanced electrolyte solutions and the vasopressor noradrenaline. Because there is little scientific evidence for the use of alternative drugs, these should only be given if there is a good pathophysiologic rationale and if their effect is continuously monitored and re-evaluated.


Assuntos
Choque , Hidratação , Hemodinâmica , Humanos , Monitorização Fisiológica , Norepinefrina , Choque/tratamento farmacológico , Vasoconstritores/efeitos adversos
5.
J Evid Based Dent Pract ; 21(2): 101569, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34391560

RESUMO

BACKGROUND: Coronary disease and Hypertension are highly prevalent health problems worldwide, with the latter being one of the most common diseases in patients visiting dental clinics. Local anesthetics (LAs) with vasoconstrictor agents (VC) are known to be commonly used in dental practice. For the above-mentioned reasons, dentists should know how to adapt and treat patients with these hazardous conditions. OBJECTIVE: The aim of this study was to find out if the use of local anesthetics (LAs) in combination with vasoconstrictor (VC) agents in dental treatment presents a risk in patient with a known history of Hypertension and/or Coronary disease. MATERIALS AND METHODS: This systematic review was conducted in accordance with The PRISMA guidelines and registered on the PROSPERO database (CRD42020187369). The search strategy was based on Mesh terms, Boolean operator AND, and the PICO model. It was designed to identify all the randomized clinical trials (RCTs) published in the last 30 years, which assessed whether the use of LA with VC agents in dental treatment produces a significant increase/decrease in hemodynamics in patients with known history of Hypertension and/or Coronary disease. The Cochrane Collaboration's tool was used to assess risk of bias of the included RCTs. RESULTS: An initial electronic search resulted in 87 papers; however only 9 RCTs met the inclusion criteria. There was a total of 482 subjects (N = 482), of which 412 had a known history of Hypertension or Coronary disease. CONCLUSIONS: According to the literature reviewed, the use of 1 to 2 cartridges of local anesthetics with 1:80,000, 1:100,000 or 1:200,000 epinephrine in patients with controlled Hypertension and/ or Coronary disease is safe. Randomized clinical trials are essential in determining the safety or risks associated with the use of LAs with VC agents in patients with poorly controlled Hypertension and Coronary disease.


Assuntos
Doença da Artéria Coronariana , Hipertensão , Anestésicos Locais , Assistência Odontológica , Humanos , Hipertensão/tratamento farmacológico , Vasoconstritores
6.
Anaesth Intensive Care ; 49(4): 275-283, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34392707

RESUMO

Vasopressors are ubiquitous in intensive care units. While central venous catheters are the preferred route of infusion, recent evidence suggests peripheral administration may be safe for short, single-agent courses. Here, we identify risk factors and develop a predictive model for patient central venous catheter requirement using the Medical Information Mart for Intensive Care, a single-centre dataset of patients admitted to an intensive care unit between 2008 and 2019. Using prior literature, a composite endpoint of prolonged single-agent courses (>24 hours) or multi-agent courses of any duration was used to identify likely central venous catheter requirement. From a cohort of 69,619 intensive care unit stays, there were 17,053 vasopressor courses involving one or more vasopressors that met study inclusion criteria. In total, 3807 (22.3%) vasopressor courses involved a single vasopressor for less than six hours, 7952 (46.6%) courses for less than 24 hours and 5757 (33.8%) involved multiple vasopressors of any duration. Of these, 3047 (80.0%) less than six-hour and 6423 (80.8%) less than 24-hour single vasopressor courses used a central venous catheter. Logistic regression models identified associations between the composite endpoint and intubation (odds ratio (OR) 2.36, 95% confidence intervals (CI) 2.16 to 2.58), cardiac diagnosis (OR 0.72, CI 0.65 to 0.80), renal impairment (OR 1.61, CI 1.50 to 1.74), older age (OR 1.002, Cl 1.000 to 1.005) and vital signs in the hour before initiation (heart rate, OR 1.006, CI 1.003 to 1.009; oxygen saturation, OR 0.996, CI 0.993 to 0.999). A logistic regression model predicting the composite endpoint had an area under the receiver operating characteristic curve (standard deviation) of 0.747 (0.013) and an accuracy of 0.691 (0.012). This retrospective study reveals a high prevalence of short vasopressor courses in intensive care unit settings, a majority of which were administered using central venous catheters. We identify several important risk factors that may help guide clinicians deciding between peripheral and central venous catheter administration, and present a predictive model that may inform future prospective trials.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Idoso , Cateterismo Venoso Central/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , Fatores de Risco , Vasoconstritores
7.
FASEB J ; 35(9): e21877, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34449098

RESUMO

Although commonly thought to produce prostacyclin (prostaglandin I2 ; PGI2 ) that evokes vasodilatation and protects vessels from the development of diseases, the endothelial cyclooxygenase (COX)-mediated metabolism has also been found to release substance(s) called endothelium-derived contracting factor(s) (EDCF) that causes endothelium-dependent contraction and implicates in endothelial dysfunction of disease conditions. Various mechanisms have been proposed for the process; however, the major endothelial COX metabolite PGI2 , which has been classically considered to activate the I prostanoid receptor (IP) that mediates vasodilatation and opposes the effects of thromboxane (Tx) A2 produced by COX in platelets, emerges as a major EDCF in health and disease conditions. Our recent studies from genetically altered mice further suggest that vasomotor reactions to PGI2 are collectively modulated by IP, the vasoconstrictor Tx-prostanoid receptor (TP; the prototype receptor of TxA2 ) and E prostanoid receptor-3 (EP3; a vasoconstrictor receptor of PGE2 ) although with differences in potency and efficacy; a contraction to PGI2 reflects activities of TP and/or EP3 outweighing that of the concurrently activated IP. Here, we discuss the history of endothelium-dependent contraction, evidences that support the above hypothesis, proposed mechanisms for the varied reactions to endothelial PGI2 synthesis as well as the relation of its dilator activity to the effect of another NO-independent vasodilator mechanism, the endothelium-derived hyperpolarizing factor. Also, we address the possible pathological and therapeutic implications as well as questions remaining to be resolved or limitations of our above findings obtained from genetically altered mouse models.


Assuntos
Endotélio Vascular/metabolismo , Epoprostenol/metabolismo , Vasoconstrição/fisiologia , Animais , Endotélio Vascular/efeitos dos fármacos , Humanos , Camundongos , Prostaglandinas/metabolismo , Receptores de Prostaglandina/metabolismo , Receptores de Tromboxanos/metabolismo , Tromboxanos/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Sistema Vasomotor/efeitos dos fármacos , Sistema Vasomotor/metabolismo
9.
Am J Cardiol ; 153: 101-108, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34210502

RESUMO

Pulmonary hypertension (PH) is common in patients with left heart disease and is present in varying degrees in patients with severe mitral valve disease. There is paucity of data regarding outcomes following transcatheter mitral valve repair (TMVr) in patients with PH. For this study, we analyzed NIS data from 2014 to 2018 using the ICD-9-CM and 10-CM codes. Baseline characteristics were compared using a Pearson chi-squared test for categorical variables and independent samples t-test for continuous variables. To account for selection bias, a 1:1 propensity match cohort was derived using logistic regression. Trend analysis was- done using linear regression. Of 21,505 encounters, 6780 encounters had PH. 6610 PH encounters were matched with 6610 encounters without PH. In-hospital mortality (3.3% versus 1.9%, p <0.01) was higher in PH population. Complications such as blood transfusion (3.6% versus 1.7%, p <0.01), GI bleed (1.4% versus 1%, p = 0.04), vascular complications (5.3% versus 3.3%, p <0.01), vasopressors use (2.9% versus 1.7%, p <0.01) and pacemaker placement (1.3% versus 0.8%, p = 0.01) remained significantly higher for encounters with PH. Multiple Logistic regression showed PH was associated with higher mortality (adjusted odds ratio [AOR], 1.68 [95% confidence interval [CI], 1.39-2.05], p <0.01). The mean length of stay (6.2 versus 5.3 days, p <0.01) and cost per hospitalization ($53,780 versus $50,801, p <0.01) remained significantly higher in the PH group when compared to group without PH. In conclusion, TMVr in PH as compared to without PH is associated with higher mortality, post-procedure complication rates, length of stay, and cost of stay.


Assuntos
Cateterismo Cardíaco , Mortalidade Hospitalar , Hipertensão Pulmonar/epidemiologia , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue/estatística & dados numéricos , Comorbidade , Feminino , Hemorragia Gastrointestinal/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Insuficiência da Valva Mitral/epidemiologia , Razão de Chances , Marca-Passo Artificial , Hemorragia Pós-Operatória/epidemiologia , Vasoconstritores/uso terapêutico
13.
J Card Surg ; 36(10): 3711-3718, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34310744

RESUMO

BACKGROUND AND AIM OF THE STUDY: Although dopamine and norepinephrine are recommended as first-line agents in the treatment of shock, it is unclear which is the optimal vasoactive inotropic agent (VIA) to manage postcardiotomy circulatory shock. This single-center, randomized clinical trial aimed to investigate the efficacy and safety of dopamine versus norepinephrine in postcardiotomy circulatory shock. METHODS: We randomly assigned the patients with postcardiotomy circulatory shock to receive either dopamine or norepinephrine. When shock persisted despite the dose of 20 µg/kg/min of dopamine or the dose of 0.2 µg/kg/min of norepinephrine, epinephrine or vasopressin could be added. The primary endpoint was new-onset tachyarrhythmic event during drug infusion. Secondary endpoints included requirement of additional VIAs, postoperative complications, and all-cause mortality within 30 days of drug initiation. RESULTS: At the planned interim analysis of 100 patients, the boundary for the benefit of norepinephrine has been crossed, and the study was stopped early. Excluding two patients withdrawing a consent, 48 patients were assigned to dopamine and 50 patients to norepinephrine. New-onset tachyarrhythmic event occurred in 12 (25%) patients in the dopamine and one (2%) patient in the norepinephrine group (p = .009). The requirement for additional VIAs was more common in the dopamine group (p < .001). Other secondary endpoints were similar between groups. CONCLUSIONS: Despite the limited study subjects with early determination, in patients with postcardiotomy circulatory shock, dopamine as a first-line vasopressor was associated with higher tachyarrhythmic events and greater need for additional VIAs compared with norepinephrine.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Choque Séptico , Choque , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dopamina , Humanos , Norepinefrina , Choque/tratamento farmacológico , Choque/etiologia , Choque Séptico/tratamento farmacológico , Vasoconstritores , Vasopressinas
14.
Georgian Med News ; (314): 125-128, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34248041

RESUMO

Hepatorenal syndrome is a severe complication of liver cirrhosis which is difficult to treat because of a very fast course and lack of adequate dosing recommendations due to the stage of the disease. In this study we aimed to refine the treatment of hepatorenal syndrome type I by modifying the dose of terlipressin, depending on the stage of acute kidney injury (AKI). Objective - to improve the treatment method of hepatorenal syndrome type I in patients with alcoholic liver cirrhosis by selecting the dose of terlipressin depending on the stage of acute kidney injury. For this study were enrolled 161 patients with diagnosis alcoholic liver cirrhosis, complicated with the hepatorenal syndrome. All patients were were randomly divided into control (group 1) (n=79) and study (group 2) (n=82) groups depending on the treatment received (terlipressin in the standard dosage or modified by the response-guided titration method). If the serum creatinine level decreased less than 25% from the baseline, the dose of terlipressin was gradually increased but did not accede 12 mg/24 hours. The stage of AKI was diagnosed using the criteria of Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury, 2012. The risk of short term mortality (within the first 29 days) was prognosed by Model for End-Stage Liver Disease (MELD) score. The kidney function improved better in persons with a modified dose of terlipressin: the complete response rate in them was 81.7%. The response rate in those who received the standard treatment, was 66.7% only (p˂0.05). It was found that the effective dosage of terlipressin is 3 mg/24 for AKI stage I; 6 mg/24 - for AKI stage II; 12 mg/24 - for AKI stage III. The relapse of the disease occurred only in 23.2% patients with modified treatment against 40.1% in the control group (p˂0.05). Short term survival was also significantly higher in the study group - 54.9%, while in the control group it was 37% only (p˂0.05). Thus, correction of terlipressin dosage could improve the results of the treatment and reduce mortality in patients with hepatorenal syndrome type I.


Assuntos
Injúria Renal Aguda , Doença Hepática Terminal , Síndrome Hepatorrenal , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Doença Hepática Terminal/tratamento farmacológico , Síndrome Hepatorrenal/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Índice de Gravidade de Doença , Vasoconstritores/uso terapêutico
15.
BMJ Open ; 11(7): e044357, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266837

RESUMO

OBJECTIVES: There is a lack of evidence about the use of local anaesthetics (LAs) in patients with cardiovascular diseases (CVD) in dental procedures. Thus, this study evaluated the safety of using LA with vasoconstrictor to determine the risk of cardiovascular events in patients with CVD. DESIGN: Systematic review and meta-analysis. METHODS: We have searched in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid), EMBASE (via Ovid), Healthstar (via Ovid), CINAHL, Web of Science and ClinicalTrials.gov for randomised controlled trials (RCTs) up to January 2020. We have included RCTs involving adults with CVD within two groups: intervention group with LA with vasoconstrictor and control group with LA without vasoconstrictor. The primary outcomes assessed were death, mortality by a specific cause, stroke, acute myocardial infarction, hospitalisation, pain, bleeding and arrhythmias. The secondary outcomes were ST segment depression, anxiety, adverse effects and changes in haemodynamic parameters. The data were pooled using random effects meta-analyses and the confidence in the estimates was verified using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Ten RCTs (n=478 participants) were included. Most of them had a high risk of bias. There were more cases of pain and bleeding in groups without vasoconstrictor. Meta-analysis demonstrated a decrease in the systolic blood pressure with the use of LA with vasoconstrictor (standard mean difference -0.95, 95% CI -1.35 to -0.55) after procedure. Overall, for the other outcomes assessed there was no statistical difference. The quality of evidence was considered low according to the GRADE profile. CONCLUSIONS: The results suggest that the use of LA with vasoconstrictors (epinephrine in low doses) is safe in patients with some types of CVD. However, the low quality of evidence demonstrated that literature needs further studies in order to confirm these results. PROTOCOL REGISTRATION: PROSPERO (CRD42016045421).


Assuntos
Doenças Cardiovasculares , Infarto do Miocárdio , Adulto , Anestesia Local , Anestésicos Locais , Humanos , Vasoconstritores/uso terapêutico
17.
Am J Trop Med Hyg ; 105(3): 596-599, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34280133

RESUMO

This retrospective and single-center study in Reunion Island (Indian Ocean) assessed frequency, mortality, causative pathogens of severe necrotizing skin, and necrotizing skin and soft tissue infections (NSSTIs) admitted in intensive care unit (ICU). Sixty-seven consecutive patients were included from January 2012 to December 2018. Necrotizing skin and soft tissue infection represented 1.06% of total ICU admissions. We estimate the incidence of NSSTI requiring ICU at 1.21/100,000 person/years in Reunion Island. Twenty (30%) patients were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) prior to admission in ICU and 40 (60%) were diagnosed patients with diabetes. Sites of infection were the lower limb in 52 (78%) patients, upper limb in 4 (6%), and perineum in 10 (15%). The surgical treatment was debridement for 40 patients, whereas 11 patients required an amputation. The most commonly isolated microorganisms were Streptococci (42%) and Gram-negative bacteria (22%).The mortality rate was 25.4%. NSAIDs did not influence mortality when interrupted upon admission to ICU.


Assuntos
Fasciite Necrosante/epidemiologia , Choque Séptico/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções Estreptocócicas/epidemiologia , Idoso , Amputação , Anti-Inflamatórios não Esteroides/uso terapêutico , Arterite/epidemiologia , Comorbidade , Desbridamento , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Fasciite Necrosante/mortalidade , Fasciite Necrosante/terapia , Feminino , Hidratação , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Negativas/terapia , Mortalidade Hospitalar , Humanos , Hipertensão/epidemiologia , Hipoglicemiantes/uso terapêutico , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Necrose , Insuficiência Renal Crônica/epidemiologia , Terapia de Substituição Renal , Respiração Artificial , Estudos Retrospectivos , Reunião/epidemiologia , Fatores de Risco , Choque Séptico/mortalidade , Choque Séptico/terapia , Dermatopatias Infecciosas , Infecções dos Tecidos Moles/mortalidade , Infecções dos Tecidos Moles/terapia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/terapia , Staphylococcus aureus , Infecções Estreptocócicas/mortalidade , Infecções Estreptocócicas/terapia , Streptococcus , Streptococcus pyogenes , Vasoconstritores/uso terapêutico
18.
Am J Physiol Heart Circ Physiol ; 321(2): H382-H389, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34142888

RESUMO

Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. In contrast to wild-type controls, Dusp5 null mice infused with ANG II developed PH and right ventricular (RV) hypertrophy. PH in Dusp5 null mice was associated with thickening of the medial layer of small PAs, suggesting an in vivo role for DUSP5 as a negative regulator of ANG II-dependent SMC proliferation. Consistent with this, overexpression of DUSP5 blocked ANG II-mediated proliferation of cultured human pulmonary artery SMCs (hPASMCs) derived from patients with idiopathic PH or from failed donor controls. Collectively, the data support a role for DUSP5 as a feedback inhibitor of ANG II-mediated ERK signaling and PASMC proliferation and suggest that disruption of this circuit leads to adverse cardiopulmonary remodeling.NEW & NOTEWORTHY Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism.


Assuntos
Proliferação de Células/genética , Fosfatases de Especificidade Dupla/genética , Ventrículos do Coração/metabolismo , Hipertensão Pulmonar/genética , Hipertrofia Ventricular Direita/genética , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , Remodelação Vascular/genética , Angiotensina II/farmacologia , Animais , Estudos de Casos e Controles , Células Cultivadas , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/fisiopatologia , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Knockout , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Vasoconstritores/farmacologia
19.
Am J Physiol Heart Circ Physiol ; 321(2): H339-H352, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34170194

RESUMO

Electronic cigarettes (E-cigs) have been promoted as harm-free or less risky than smoking, even for women during pregnancy. These claims are made largely on E-cig aerosol having fewer number of toxic chemicals compared with cigarette smoke. Given that even low levels of smoking are found to produce adverse birth outcomes, we sought to test the hypothesis that vaping during pregnancy (with or without nicotine) would not be harm-free and would result in vascular dysfunction that would be evident in offspring during adolescent and/or adult life. Pregnant female Sprague Dawley rats were exposed to E-cig aerosol (1 h/day, 5 days/wk, starting on gestational day 2 until pups were weaned) using e-liquid with 0 mg/mL (E-cig0) or 18 mg/mL nicotine (E-cig18) and compared with ambient air-exposed controls. Body mass at birth and at weaning were not different between groups. Assessment of middle cerebral artery (MCA) reactivity revealed a 51%-56% reduction in endothelial-dependent dilation response to acetylcholine (ACh) for both E-cig0 and E-cig18 in 1-mo, 3-mo (adolescent), and 7-mo-old (adult) offspring (P < 0.05 compared with air, all time points). MCA responses to sodium nitroprusside (SNP) and myogenic tone were not different across groups, suggesting that endothelial-independent responses were not altered. The MCA vasoconstrictor response (5-hydroxytryptamine, 5-HT) was also not different across treatment and age groups. These data demonstrate that maternal vaping during pregnancy is not harm-free and confers significant cerebrovascular health risk/dysfunction to offspring that persists into adult life. NEW & NOTEWORTHY These data established that vaping electronic cigarettes during pregnancy, with or without nicotine, is not safe and confers significant risk potential to the cerebrovascular health of offspring in early and adult life. A key finding is that vaping without nicotine does not protect offspring from cerebrovascular dysfunction and results in the same level of cerebrovascular dysfunction (compared with maternal vaping with nicotine), indicating that the physical and/or chemical properties from the base solution (other than nicotine) are responsible for the cerebrovascular dysfunction that we observed. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/maternal-vaping-impairs-vascular-function-in-theoffspring/.


Assuntos
Vapor do Cigarro Eletrônico/farmacologia , Artéria Cerebral Média/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Vaping , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Aerossóis , Animais , Sistemas Eletrônicos de Liberação de Nicotina , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Artéria Cerebral Média/fisiopatologia , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Nitroprussiato/farmacologia , Gravidez , Ratos , Serotonina/farmacologia , Vasoconstrição/fisiologia , Vasoconstritores/farmacologia , Vasodilatação/fisiologia , Vasodilatadores/farmacologia
20.
Artigo em Alemão | MEDLINE | ID: mdl-34187073

RESUMO

Vasopressors are widely used in anaesthesiology and critical care medicine, to treat harmless (e.g. anaesthesia-induced hypotension) as well as life-threatening conditions (e.g. septic shock). Some clinically used vasopressors resemble endogenous substances - such as norepinephrine - while others have been artificially synthesized (e.g. phenylephrine). Most of the substances used in different clinical scenarios have various effects except for vasoconstriction alone. Therefore, a thorough understanding of the pharmacology and clinical profile of every single substance is of highest importance prior to practical usage. Furthermore, the fundamentals of vascular physiology and vasotonic regulation are mandatory to safely provide vasopressor-based therapies. This article covers the essentials of physiology and pharmacology of vasopressors, and the clinical settings they are used in (e.g. septic shock, vasoplegic shock after cardiac surgery, trauma-induced hypotension).


Assuntos
Choque Séptico , Choque , Humanos , Norepinefrina , Fenilefrina , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico
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