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1.
Nat Commun ; 11(1): 5555, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144559

RESUMO

It is highly debated how cyclic adenosine monophosphate-dependent regulation (CDR) of the major pacemaker channel HCN4 in the sinoatrial node (SAN) is involved in heart rate regulation by the autonomic nervous system. We addressed this question using a knockin mouse line expressing cyclic adenosine monophosphate-insensitive HCN4 channels. This mouse line displayed a complex cardiac phenotype characterized by sinus dysrhythmia, severe sinus bradycardia, sinus pauses and chronotropic incompetence. Furthermore, the absence of CDR leads to inappropriately enhanced heart rate responses of the SAN to vagal nerve activity in vivo. The mechanism underlying these symptoms can be explained by the presence of nonfiring pacemaker cells. We provide evidence that a tonic and mutual interaction process (tonic entrainment) between firing and nonfiring cells slows down the overall rhythm of the SAN. Most importantly, we show that the proportion of firing cells can be increased by CDR of HCN4 to efficiently oppose enhanced responses to vagal activity. In conclusion, we provide evidence for a novel role of CDR of HCN4 for the central pacemaker process in the sinoatrial node.


Assuntos
Relógios Biológicos , AMP Cíclico/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Nó Sinoatrial/patologia , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/patologia , Relógios Biológicos/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/complicações , Bradicardia/patologia , Carbacol/farmacologia , Eletrocardiografia , Feminino , Células HEK293 , Coração/efeitos dos fármacos , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Subunidades Proteicas/metabolismo , Reprodutibilidade dos Testes , Nó Sinoatrial/fisiopatologia , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiopatologia
2.
Medicine (Baltimore) ; 99(45): e23061, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157963

RESUMO

OBJECTIVE: This study is aims to compare the anesthetic safety of propofol combined with etomidate for painless gastroscopy. METHODS: Three hundred patients undergoing painless gastroscopy were randomly assigned to P, PE1, and PE2 groups. Patients were anesthetized with propofol (P group) or propofol combined with etomidate (volume ratio 1: 1, PE1 group; volume ratio 2: 1, PE2 group). The hemodynamics and adverse reactions were observed. The sleep quality satisfaction and nature of dreams were recorded. RESULTS: Compared with pre-anesthesia, the mean arterial pressure and heart rate of the 3 groups were significantly slower during the examination and at the end of the examination. PE1 group had a higher incidence of muscle spasm, body moving, choking, and deglutition. The incidence of hypoxemia and injection pain was higher in P group. P and PE2 group had higher sleep quality satisfaction and dream incidence after awaking. However, there was no difference in the nature of dreams among 3 groups. CONCLUSION: Our data indicate that the combination of 10 ml 1.0% propofol and 5 ml 0.2% etomidate for painless gastroscopy reduces adverse reactions while not affecting the patients respiratory function. Moreover, it is safe and effective, which is worthy of clinical application and promotion.


Assuntos
Anestésicos Intravenosos/efeitos adversos , Etomidato/efeitos adversos , Gastroscopia/métodos , Propofol/efeitos adversos , Adulto , Obstrução das Vias Respiratórias/induzido quimicamente , Anestésicos Intravenosos/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Estudos de Casos e Controles , Quimioterapia Combinada , Etomidato/administração & dosagem , Feminino , Gastroscopia/tendências , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Hipóxia/induzido quimicamente , Incidência , Reação no Local da Injeção , Masculino , Pessoa de Meia-Idade , Mioclonia/induzido quimicamente , Propofol/administração & dosagem , Segurança , Espasmo/induzido quimicamente , Espasmo/epidemiologia , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(43): e22288, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120732

RESUMO

INTRODUCTION: Dexmedetomidine and midazolam have become important approaches for the sedation of dental surgery. However, the comparison of these 2 drugs for the sedation of dental surgery has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of dexmedetomidine versus midazolam for dental surgery. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of dexmedetomidine versus midazolam on dental surgery are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model. RESULTS: Five RCTs and 420 patients are included in the meta-analysis. Compared with midazolam intervention for dental surgery, dexmedetomidine intervention has similar lowest SpO2, lowest heart rate and lowest systolic blood pressure, duration of surgery, and total volume of local anesthetic, but is associated with stable and reduced lowest diastolic blood pressure. CONCLUSIONS: Similar benefits of dexmedetomidine and midazolam intervention are observed for the sedation of dental surgery in terms of SpO2, heart rate, systolic blood pressure, and the volume of local anesthetic, but dexmedetomidine may result in more stable diastolic blood pressure.


Assuntos
Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Midazolam/uso terapêutico , Procedimentos Cirúrgicos Bucais , Anestésicos Locais/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Diástole/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Duração da Cirurgia , Oxigênio/sangue , Sístole/efeitos dos fármacos
4.
Cardiovasc Ther ; 2020: 8563135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123219

RESUMO

Metabolic syndrome (MetS) is a combination of factors which, collectively, increase cardiovascular risk to a greater extent than each of them separately. Previous studies showed high cardiovascular risk to be associated with autonomic nervous system dysfunction. The purpose of this study was to assess the effects of antihypertensive treatment on heart rate variability (HRV) in patients with hypertension (HTN), depending on cooccurrence of MetS. 118 patients with uncontrolled HTN were enrolled to the study. HRV was compared among patients with and without MetS (MetS [+], n = 70) at baseline and following 12 months antihypertensive treatment. The HRV indices measured from RR intervals recorded form using 24-hour ambulatory electrocardiography. The measured HRV domains were the standard deviation of the average of NN intervals [SDNN], square root of the mean of the sum of the squares of differences between adjacent NN intervals [rMSSD], percentage of NN50 [pNN50], low frequency [LF], high frequency [HF], total power of variance of all NN intervals [TP], and LF/HF ratio. Baseline parameters: SDNN, rMSSD, pNN50, and HF were significantly lower in the MetS[+] compared to the MetS[-] subgroup (p < 0.05). After a 12-month antihypertensive treatment, MetS[+] patients achieved a significant improvement in parameters: SDNN, rMSSD, pNN50, and TP (p < 0.05), while the changes in HRV observed in the MetS[-] subgroup were not statistically significant. The cooccurrence of HTN and other components of MetS is associated with disturbances of the autonomic balance. HTN control has a beneficial effect on HRV, with the effect being more evident in patients with MetS.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Adulto , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
5.
J Cardiothorac Surg ; 15(1): 296, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008451

RESUMO

BACKGROUND: The Surgical Pleth Index (SPI) is a monitoring method that reflects painful stimuli during general anesthesia, and dexmedetomidine is an analgesic adjuvant with an opioid-sparing effect. But up to now, it is still unclear whether dexmedetomidine has any influence on SPI. To investigate whether dexmedetomidine has an effect on SPI during video-assisted thoracoscopic surgery. METHODS: We enrolled 94 patients who underwent video-assisted thoracoscopic lung lobectomy. Patients were randomly assigned to a dexmedetomidine group (dexmedetomidine: 0.8 µg/kg administered for 10 min before anesthesia) or normal saline group (equal volume of normal saline). SPI and vital signs were recorded. The number rating scale (NRS) pain score was also evaluated. RESULTS: SPI values were significantly lower in the dexmedetomidine group than in the normal saline group at intubation and at discharge from the postanesthesia care unit. Compared with the normal saline group, mean arterial pressure and heart rate were both significantly lower in the dexmedetomidine group at intubation. Heart rate was lower at skin incision in the dexmedetomidine group. The NRS score in the normal saline group was noticeably higher vs. the dexmedetomidine group at discharge from the postanesthesia care unit. CONCLUSIONS: Dexmedetomidine decreased intraoperative SPI and NRS scores. Our results showed that dexmedetomidine attenuated noxious stimuli. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-OOC-16009450 , Registered 16 October, 2016.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Dexmedetomidina/uso terapêutico , Pneumopatias/cirurgia , Adolescente , Adulto , Idoso , Anestesia Geral , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória , Pneumonectomia , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida , Adulto Jovem
6.
Anesth Analg ; 131(5): 1599-1606, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079884

RESUMO

BACKGROUND: Oxycodone has been shown to be an effective analgesic for early postoperative analgesia, especially for abdominal operations associated with severe visceral pain. However, the dose needed varies depending on the operation and application of multimodal analgesia, such as local ropivacaine wound infiltration. Therefore, we conducted this study to estimate the median effective dose (ED50) of oxycodone that provides analgesia for hysterectomy and myomectomy with local ropivacaine wound infiltration. METHODS: In this dose-finding study, the ED50 of oxycodone for postoperative analgesia was estimated separately for laparoscopic hysterectomy, transabdominal hysterectomy, laparoscopic myomectomy, and transabdominal myomectomy. We used the sequential allocation designed by Dixon. Trials were conducted simultaneously in the 4 surgical type groups. A predefined dose of oxycodone was injected 30 minutes before the end of the operation with an initial dose of 0.1 mg/kg. A series of trials were performed following the rule of a relative 10% increase in dose after inadequate analgesia and a relative 10% decrease in dose after adequate analgesia. The study was conducted until the collection of 7 crossover points was achieved. Local ropivacaine wound infiltration was administered during abdominal stitching. The mean blood pressure (MBP) and heart rate (HR) were analyzed to assess the hemodynamic changes associated with oxycodone administration. RESULTS: A total of 113 patients were included in the estimation of ED50: 28 each in the laparoscopic hysterectomy group and transabdominal myomectomy group, 27 in the transabdominal hysterectomy group, and 30 in the laparoscopic myomectomy group. The estimated oxycodone ED50 (95% confidence interval [CI]) after laparoscopic hysterectomy, transabdominal hysterectomy, laparoscopic myomectomy, and transabdominal myomectomy was 0.060 mg/kg (0.053-0.068), 0.079 mg/kg (0.072-0.086), 0.060 mg/kg (0.051-0.071), and 0.092 mg/kg (0.086-0.098), respectively, for postoperative analgesia with local ropivacaine wound infiltration. The ED50 of oxycodone was different between laparoscopic surgeries and transabdominal surgeries (P < .001). The MBP and HR before and after oxycodone injection were different, regardless of surgical type. CONCLUSIONS: The oxycodone ED50 for postoperative analgesia was lower for laparoscopic hysterectomy (0.060 mg/kg) and laparoscopic myomectomy (0.060 mg/kg) than for transabdominal hysterectomy (0.079 mg/kg) and transabdominal myomectomy (0.092 mg/kg) when combined with local ropivacaine wound infiltration. A single intravenous injection of oxycodone is associated with an acceptable decrease in MBP and HR within a short time.


Assuntos
Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/uso terapêutico , Histerectomia/efeitos adversos , Oxicodona/administração & dosagem , Oxicodona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Ropivacaina/uso terapêutico , Miomectomia Uterina/efeitos adversos , Adulto , Anestesia Local , Anestésicos Locais/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Injeções Intravenosas , Laparoscopia , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Ropivacaina/administração & dosagem
7.
Cochrane Database Syst Rev ; 10: CD012569, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089502

RESUMO

BACKGROUND: Renin inhibitors (RIs) reduce blood pressure more than placebo, with the magnitude of this effect thought to be similar to that for angiotensin converting enzyme (ACE) inhibitors. However, a drug's efficacy in lowering blood pressure cannot be considered as a definitive indicator of its effectiveness in reducing mortality and morbidity. The effectiveness and safety of RIs compared to ACE inhibitors in treating hypertension is unknown. OBJECTIVES: To evaluate the benefits and harms of renin inhibitors compared to ACE inhibitors in people with primary hypertension. SEARCH METHODS: The Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to August 2020: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers about further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We included randomized, active-controlled, double-blinded studies (RCTs) with at least four weeks follow-up in people with primary hypertension, which compared renin inhibitors with ACE inhibitors and reported morbidity, mortality, adverse events or blood pressure outcomes. We excluded people with proven secondary hypertension. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis. MAIN RESULTS: We include 11 RCTs involving 13,627 participants, with a mean baseline age from 51.5 to 74.2 years. Follow-up duration ranged from four weeks to 36.6 months. There was no difference between RIs and ACE inhibitors for the outcomes: all-cause mortality: risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.18; 5 RCTs, 5962 participants; low-certainty evidence; total myocardial infarction: RR 0.86, 95% CI 0.22 to 3.39; 2 RCTs, 957 participants; very low-certainty evidence; adverse events: RR 0.98, 95% CI 0.93 to 1.03; 10 RTCs, 6007 participants;  moderate-certainty evidence; serious adverse events: RR 1.21, 95% CI 0.89 to 1.64; 10 RTCs, 6007 participants; low-certainty evidence; and withdrawal due to adverse effects: RR 0.85, 95% CI 0.68 to 1.06; 10 RTCs, 6008 participants; low-certainty evidence. No data were available for total cardiovascular events, heart failure, stroke, end-stage renal disease or change in heart rate. Low-certainty evidence suggested that RIs reduced systolic blood pressure: mean difference (MD) -1.72, 95% CI -2.47 to -0.97; 9 RCTs, 5001 participants;  and diastolic blood pressure: MD -1.18, 95% CI -1.65 to -0.72; 9 RCTs, 5001 participants,  to a greater extent than ACE inhibitors, but we judged this to be more likely due to bias than a true effect.  AUTHORS' CONCLUSIONS: For the treatment of hypertension, we have low certainty that renin inhibitors (RI) and angiotensin converting enzyme (ACE) inhibitors do not differ for all-cause mortality and myocardial infarction. We have low to moderate certainty that they do not differ for adverse events. Small reductions in blood pressure with renin inhibitors compared to ACE inhibitors are of low certainty.  More independent, large, long-term trials are needed to compare RIs with ACE inhibitors, particularly assessing morbidity and mortality outcomes, but also on blood pressure-lowering effect.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Renina/antagonistas & inibidores , Idoso , Amidas/efeitos adversos , Amidas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Feminino , Fumaratos/efeitos adversos , Fumaratos/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Irbesartana/uso terapêutico , Falência Renal Crônica/epidemiologia , Lisinopril/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ramipril/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Ecotoxicol Environ Saf ; 205: 111339, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961491

RESUMO

Famoxadone-cymoxanil is a new protective and therapeutic fungicide, but little research has been done on it or its toxicity in aquatic organisms. In this study, we used zebrafish to investigate the cardiotoxicity of famoxadone-cymoxanil and the potential mechanisms involved. Zebrafish embryos were exposed to different concentrations of famoxadone-cymoxanil until 72 h post-fertilization (hpf), then changes of heart morphology in zebrafish embryos were observed. We also detected the levels of oxidative stress, myocardial-cell proliferation and apoptosis, ATPase activity, and the expression of genes related to the cardiac development and calcium-signaling pathway. After famoxadone-cymoxanil exposure, pericardial edema, cardiac linearization, and reductions in the heart rate and cardiac output positively correlated with concentration. Although myocardial-cell apoptosis was not detected, proliferation of the cells was severely reduced and ATPase activity significantly decreased, resulting in a severe deficiency in heart function. In addition, indicators of oxidative stress changed significantly after exposure of the embryos to the fungicide. To better understand the possible molecular mechanisms of cardiovascular toxicity in zebrafish, we studied the transcriptional levels of cardiac development, calcium-signaling pathways, and genes associated with myocardial contractility. The mRNA expression levels of key genes in heart development were significantly down-regulated, while the expression of genes related to the calcium-signaling pathway (ATPase [atp2a1], cardiac troponin C [tnnc1a], and calcium channel [cacna1a]) was significantly inhibited. Expression of klf2a, a major endocardial flow-responsive gene, was also significantly inhibited. Mechanistically, famoxadone-cymoxanil toxicity might be due to the downregulation of genes associated with the calcium-signaling pathway and cardiac muscle contraction. Our results found that famoxadone-cymoxanil exposure causes cardiac developmental toxicity and severe energy deficiency in zebrafish.


Assuntos
Acetamidas/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Coração/efeitos dos fármacos , Estrobilurinas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Cardiotoxicidade , Regulação para Baixo , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Coração/embriologia , Frequência Cardíaca/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
10.
PLoS One ; 15(9): e0239473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997682

RESUMO

BACKGROUND: Fibromyalgia patients experience cardiovascular complications in addition to musculoskeletal pain. This study aimed to investigate the cardiac effects of a prolonged shallow water gait in a fibromyalgia-induced young mouse model. METHODS: To produce a fibromyalgia mouse model, wild-type mice were administered an intraperitoneal injection of reserpine once a day for three days, and two primary experiments were performed. First, three types of gait tests were performed before and after the reserpine injections as follows: (i) 5 minutes of free gait outside the water, (ii) 1 minute of free gait in shallow warm water, and (iii) 5 minutes of free gait in shallow warm water. Second, electrocardiogram recordings were taken before and after the three gait tests. The average heart rate and heart rate irregularity scores were analyzed. RESULTS: Exercise-induced cardiac arrhythmia was observed at 1-minute gait in shallow water during the acute stage of induced FM in young mice. Further, both cardiac arrhythmia and a decrease in HR have occurred at 5-minute gait in shallow water at the same mice. However, this phenomenon was not observed in the wild-type mice under any test conditions. CONCLUSION: Although a short-term free gait in shallow warm water may be advantageous for increasing the motor activity of FM-model mice, we should be aware of the risk of prolonged and excessive exercise-induced cardiac arrhythmia. For gait exercises in shallow water as a treatment in FM patients. We suggest a gradual increase in exercise duration may be warranted.


Assuntos
Arritmias Cardíacas/fisiopatologia , Fibromialgia/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Modelos Animais de Doenças , Marcha/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Reserpina/farmacologia
11.
Life Sci ; 260: 118432, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941895

RESUMO

AIMS: Biological, psychosocial and lifestyle risk factors interact in the development of type 2 diabetes mellitus (T2DM). To date, the effects of sex, chronic stress (CS) and high-fat diet (HFD) on T2DM and the ability of linalyl acetate (LA) to prevent T2DM have not been determined. This study therefore explored the differential effects of CS and HFD on T2DM, as well as the ability of LA to prevent T2DM development, in male and female rats. MAIN METHODS: T2DM was induced in rats by feeding an HFD and placing them under immobilization stress for 2 h/day for 3 weeks. Low-dose streptozotocin was administered on day 15, and LA was administered for 3 weeks. KEY FINDINGS: Fasting blood sugar (FBS) increased in HFD-fed male, but not female, rats. CS further increased FBS in HFD-fed rats, whereas CS alone did not alter FBS. The homeostatic model assessment-insulin resistance (HOMA-IR) showed results similar to FBS. Serum corticosterone levels markedly increased only in HFD-fed male rats exposed to CS. Pancreas nuclear factor kappa B (NF-κB) levels were higher in HFD-fed male rats exposed to CS than in control rats although there were no sex differences. LA 10 mg/kg significantly reduced FBS, serum insulin, HOMA-IR, and serum corticosterone levels in HFD-fed male rats exposed to CS. LA 10 mg/kg also tended to reduce NF-κB in the pancreas and significantly increased mitochondrial membrane potential (MMP) in the liver. SIGNIFICANCE: Male rats are vulnerable to T2DM induced by CS and HFD, and LA can prevent T2DM in these rats not only by reducing insulin resistance and corticosterone levels but by increasing MMP in the liver.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Monoterpenos/farmacologia , Animais , Corticosterona/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Insulina/sangue , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Fatores Sexuais , Estreptozocina/administração & dosagem , Estreptozocina/toxicidade , Estresse Fisiológico
12.
Ecotoxicol Environ Saf ; 203: 110994, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888603

RESUMO

The effects of cyanobacteria (Aphanizomenon flos-aquae (90%), Microcystis aeruginosa) and dense Elodea canadensis beds on the health endpoints of the amphipod Gmelinoides fasciatus and bivalve mollusc Unio pictorum were examined in mesocosms with simulated summer conditions (July-August 2018) in the environment of the Rybinsk Reservoir (Volga River Basin, Russia). Four treatments were conducted, including one control and three treatments with influencing factors, cyanobacteria and dense elodea beds (separately and combined). After 20 days of exposure, we evaluated the frequency of malformed and dead embryos in amphipods, heart rate (HR) and its recovery (HRR) after stress tests in molluscs as well as heat tolerance (critical thermal maximum or CTMax) in both amphipods and molluscs. The significant effect, such as elevated number of malformed embryos, was recorded after exposure with cyanobacteria (separately and combined with elodea) and presence of microcystins (MC) in water (0.17 µg/l, 40% of the most toxic MC-LR contribution). This study provided evidence that an elevated number (>5% of the total number per female) of malformed embryos in amphipods showed noticeable toxicity effects in the presence of cyanobacteria. The decreased oxygen under the influence of dense elodea beds led to a decrease in HR (and an increase in HRR) in molluscs. The notable effects on all studied biomarkers, embryo malformation frequency and heat tolerance in the amphipod G. fasciatus, as well as the heat tolerance and heart rate in the mollusc U. pictorum, were found when both factors (elodea and cyanobacteria) were combined. The applied endpoints could be further developed for environmental monitoring, but the obtained results support the importance of the combined use of several biomarkers and species, especially in the case of multi-factor environmental stress.


Assuntos
Anfípodes/efeitos dos fármacos , Bivalves/efeitos dos fármacos , Cianobactérias/metabolismo , Monitoramento Ambiental/métodos , Hydrocharitaceae/metabolismo , Poluentes Químicos da Água/toxicidade , Anfípodes/metabolismo , Animais , Aphanizomenon/metabolismo , Biomarcadores/análise , Bivalves/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Microcistinas/metabolismo , Microcistinas/toxicidade , Microcystis/metabolismo , Federação Russa , Poluentes Químicos da Água/metabolismo
14.
Environ Health Prev Med ; 25(1): 45, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867671

RESUMO

High salt intake increases blood pressure, and dietary salt intake has been clearly demonstrated to be associated with hypertension incidence. Japanese people consume higher amounts of salt than Westerners. It has been reported that miso soup was one of the major sources of daily salt intake in Japanese people. Adding salt is indispensable to make miso, and therefore, in some cases, refraining from miso soup is recommended to reduce dietary salt intake. However, recent studies using salt-sensitive hypertensive models have revealed that miso lessens the effects of salt on blood pressure. In other word, the intake of miso dose not increase the blood pressure compared to the equivalent intake of salt. In addition, many clinical observational studies have demonstrated the absence of a relationship between the frequency of miso soup intake and blood pressure levels or hypertension incidence. The mechanism of this phenomenon seen in the subjects with miso soup intake has not been fully elucidated yet. However, in basic studies, it was found that the ingredients of miso attenuate sympathetic nerve activity, resulting in lowered blood pressure and heart rate. Therefore, this review focused on the differences between the effects of miso intake and those of the equivalent salt intake on sympathetic nerve activity, blood pressure, and heart rate.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Alimentos de Soja/efeitos adversos , Sistema Nervoso Simpático/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Sistema Nervoso Simpático/fisiologia
15.
Medicine (Baltimore) ; 99(36): e21864, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899016

RESUMO

Spinal anesthesia (SpA) for elective caesarean section (CS) is often accompanied by clinically relevant arterial hypotension. The Bezold-Jarisch reflex, causing postspinal hypotension, has been shown to be antagonized by serotonin type 3 (5-HT3) blockade. Our aim was to assess if routine prophylactic administration of the 5-HT3 antagonist ondansetron (ODS) attenuates postspinal change in maternal blood pressure.Elective CS under SpA were retrospectively analyzed. Eighty parturients having routinely received 8 mg ODS prior to SpA were compared with 80 patients having not (control group).Mean arterial blood pressure significantly decreased from baseline to the postspinal period (P < .0001) without differences in blood pressure decreases between the 2 groups. This also applied to the heart rate. Overall use of cafedrine/theodrenaline was higher in the ODS group (0.8 (0.4-1.6) mL vs 0.8 (0-1.0) mL in the control group, P = .01). APGAR values showed a presumably clinically irrelevant decrease in control group compared with the ODS group.Our results suggest that routine administration of ODS in a dosage of 8 mg does not effectively attenuate postspinal change in maternal blood pressure during CS in our setting. Given the wide variability of anesthetic techniques, only large prospective and randomized multicenter trials will ultimately serve to elucidate this issue.


Assuntos
Anestesia Obstétrica/métodos , Raquianestesia/métodos , Cesárea/métodos , Ondansetron/administração & dosagem , Antagonistas do Receptor 5-HT3 de Serotonina/administração & dosagem , Adulto , Índice de Apgar , Pressão Arterial/efeitos dos fármacos , Estudos de Casos e Controles , Cesárea/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos
16.
Cochrane Database Syst Rev ; 9: CD010054, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32888198

RESUMO

BACKGROUND: Beta-blockers are commonly used in the treatment of hypertension. We do not know whether the blood pressure (BP) lowering efficacy of beta-blockers varies across the day. This review focuses on the subclass of beta-blockers with partial agonist activity (BBPAA). OBJECTIVES: To assess the degree of variation in hourly BP lowering efficacy of BBPAA over a 24-hour period in adults with essential hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for relevant studies up to June 2020: the Cochrane Hypertension Specialised Register; CENTRAL; 2020, Issue 5; MEDLINE Ovid; Embase Ovid; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We sought to include all randomised and non-randomised trials that assessed the hourly effect of BBPAA by ambulatory monitoring, with a minimum follow-up of three weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the included trials and extracted the data. We assessed the certainty of the evidence using the GRADE approach. Outcomes included in the review were end-point hourly systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), measured using a 24-hour ambulatory BP monitoring (ABPM) device. MAIN RESULTS: Fourteen non-randomised baseline controlled trials of BBPAA met our inclusion criteria, but only seven studies, involving 121 participants, reported hourly ambulatory BP data that could be included in the meta-analysis. Beta-blockers studied included acebutalol, pindolol and bopindolol. We judged most studies at high or unclear risk of bias for selection bias, attrition bias, and reporting bias. We judged the overall certainty of the evidence to be very low for all outcomes. We analysed and presented data by each hour post-dose. Very low-certainty evidence showed that hourly mean reduction in BP and HR visually showed an attenuation over time. Over the 24-hour period, the magnitude of SBP lowering at each hour ranged from -3.68 mmHg to -17.74 mmHg (7 studies, 121 participants), DBP lowering at each hour ranged from -2.27 mmHg to -9.34 mmHg (7 studies, 121 participants), and HR lowering at each hour ranged from -0.29 beats/min to -10.29 beats/min (4 studies, 71 participants). When comparing between three 8-hourly time intervals that correspond to day, evening, and night time hours, BBPAA was less effective at lowering BP and HR at night, than during the day and evening. However, because we judged that these outcomes were supported by very low-certainty evidence, further research is likely to have an important impact on the estimate of effect and may change the conclusion. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw general conclusions about the degree of variation in hourly BP-lowering efficacy of BBPAA over a 24-hour period, in adults with essential hypertension. Very low-certainty evidence showed that BBPAA acebutalol, pindolol, and bopindolol lowered BP more during the day and evening than at night. However, the number of studies and participants included in this review was very small, further limiting the certainty of the evidence. We need further and larger trials, with accurate recording of time of drug intake, and with reporting of standard deviation of BP and HR at each hour.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Hipertensão/tratamento farmacológico , Acebutolol/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Adulto , Viés , Pressão Sanguínea/fisiologia , Ensaios Clínicos Controlados como Assunto , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pindolol/análogos & derivados , Pindolol/uso terapêutico , Fatores de Tempo
17.
Circ Arrhythm Electrophysiol ; 13(10): e008686, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907357

RESUMO

BACKGROUND: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. METHODS: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies. RESULTS: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. CONCLUSIONS: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.


Assuntos
Antivirais/administração & dosagem , Eletrocardiografia , Coração Fetal/efeitos dos fármacos , Bloqueio Cardíaco/congênito , Frequência Cardíaca/efeitos dos fármacos , Hidroxicloroquina/administração & dosagem , Antivirais/efeitos adversos , Antivirais/sangue , Cardiotoxicidade , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Sangue Fetal/metabolismo , Coração Fetal/fisiopatologia , Idade Gestacional , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Bloqueio Cardíaco/prevenção & controle , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/sangue , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Life Sci ; 259: 118210, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32763289

RESUMO

AIMS: From the synthesis of 43 lipophilic dihydropyridines, the aim of this study was to verify whether the new dihydropyridines have calcium channel affinity using coupling studies and to determine antihypertensive and antioxidant properties, as well as toxicology and toxicity nifedipine and three new compounds, were chosen from the previous results. MATERIALS AND METHODS: The animals were treated for 56 days, 28 days with N (ω) -nitro-L-arginine methyl ester to induce hypertension, and then treated for another 28 days with the new di- hydropyridine and the standard drug nifedipine. Throughout the treatment the animals had their blood pressure measured and their heart rate checked by pletysmography. After treatment the animals were euthanised, blood samples were collected for creatine kinase and urea analysis, and the brain, heart and liver were collected for oxidative status analysis (quantification of reactive oxygen species, total antioxidant capacity, and lipid peroxidation). KEY FINDINGS: Compounds 2c, and 9a, and nifedipine significantly reduced blood pressure to control group levels. The tachycardia caused by the induction of hypertension was reversed by 2c and 9a compounds. Regarding oxidative stress analyzes, the compounds that had the best performances were also 2c and 9a. Overall the results demonstrate that two of the three new dihydropyridines tested demonstrated performance equal to or superior to the standard drug nifedipine. SIGNIFICANCE: In this study, for the first time, docking was applied to analyse 43 fatty dihydropyridines regarding their calcium channel binding. Afterwards, three fatty dihydropyridines were chosen and their antihypertensive and antioxidant properties.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/ultraestrutura , Di-Hidropiridinas/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio , Di-Hidropiridinas/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/fisiopatologia , Masculino , Nifedipino/farmacologia , Piridinas/farmacologia , Ratos , Ratos Wistar
20.
PLoS One ; 15(8): e0232302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822373

RESUMO

Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 ± 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 ± 0.6 (3.4-4.5, 95% CI, n = 8), p = 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.


Assuntos
Edema/tratamento farmacológico , Peptídeos/farmacologia , Peritonite/complicações , Sepse/complicações , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Edema/complicações , Edema/patologia , Edema/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hemoglobinas/metabolismo , Interleucina-6/sangue , Lactatos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Peptídeos/uso terapêutico , Projetos Piloto , Troca Gasosa Pulmonar/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/sangue , Resistência Vascular/efeitos dos fármacos
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