RESUMEN
Acute heart failure, advanced cardiac failure, cardiac surgery, and sepsis are conditions that require simultaneous treatment to stimulate contractility and/or reduce systemic vascular resistance, with levosimendan and milrinone being treatment options. This research's aim is to review the current indications and evidence for these medications across various scenarios. Evidence suggests that levosimendan is a non-inferior alternative to dobutamine and superior to milrinone in treating low cardiac output syndrome following cardiac surgery. In cases of septic shock, levosimendan has been linked to lower mortality rates compared to placebo, while milrinone's efficacy remains inconclusive. Furthermore, postoperative patients undergoing correction for congenital heart disease have shown reduced mechanical ventilation time and intensive care unit stays when treated with levosimendan, although differences exist between the populations assigned to each intervention. In conclusion, levosimendan, compared to milrinone, appears to offer better hemodynamic favorability in patients undergoing cardiac surgery. However, additional research is necessary to further understand its impact on hemodynamic outcomes, mortality, intensive care unit, and hospital stays in patients with cardiogenic shock of both ischemic and non-ischemic etiologies, as well as septic shock.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cardiotónicos , Insuficiencia Cardíaca , Milrinona , Simendán , Humanos , Simendán/uso terapéutico , Milrinona/uso terapéutico , Milrinona/administración & dosificación , Cardiotónicos/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Hemodinámica/efectos de los fármacos , Resultado del Tratamiento , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Gasto Cardíaco Bajo/tratamiento farmacológicoRESUMEN
Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and ß-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.
Asunto(s)
Inhibidores de la Colinesterasa , Hipertensión , Contracción Miocárdica , Condicionamiento Físico Animal , Bromuro de Piridostigmina , Ratas Endogámicas SHR , Animales , Inhibidores de la Colinesterasa/farmacología , Masculino , Ratas , Contracción Miocárdica/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Bromuro de Piridostigmina/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/fisiopatología , Función Ventricular Izquierda/efectos de los fármacos , Acetilcolinesterasa/metabolismoRESUMEN
OBJECTIVE: Uncooperative behavior in pediatric dentistry is one of the most common manifestations of dental anxiety. Managing anxious patients can be attained by moderate sedation. This study aimed to compare the effect of sedation by dexmedetomidine-ketamine combination (DEX-KET) versus dexmedetomidine (DEX) on behavior of uncooperative pediatric dental patients. METHODOLOGY: In total, 56 uncooperative healthy children (3-5 years old) requiring dental treatment were divided randomly into two groups: Group I (study group), which received buccal dexmedetomidine (2 µg/kg) and ketamine (2 mg/kg), and Group II (control group), which received only buccal dexmedetomidine (4 µg/kg). Drugs effects were assessed in terms of hemodynamic parameters, patient's drug acceptance, child behavior, postoperative effect of sedation, amnesic effect, incidence of adverse events, as well as procedural induced stress measured by salivary secretory immunoglobulin A (s-IgA). RESULTS: Hemodynamic results did not reveal a statistically significant difference between the two study groups (P>0.05). There was a significant difference in patient's acceptance to sedative drug between both groups, favoring DEX (p=0.005). Children who received DEX-KET showed significantly better behavior than those who received DEX for local anesthesia (p=0.017) and during operative procedure (p=0.037). Adverse events, post-operative and amnesic effects of drugs were comparable in both groups (p>0.05). Moreover, the mean difference in the salivary s-IgA levels between initial and final value was not statistically significant between both groups (p=0.556). CONCLUSION: Both DEX-KET combination and DEX alone are effective in providing hemodynamic stability. DEX-KET combination significantly improved the behavior of sedated children compared to DEX alone but the drug acceptance was decreased in the DEX-KET group. Both regimens did not have a negative effect on postoperative behavior of children and had comparable amnesic effect with no significant adverse events. Salivary s-IgA is not considered a potential stress biomarker in sedated children.
Asunto(s)
Conducta Infantil , Ansiedad al Tratamiento Odontológico , Dexmedetomidina , Hipnóticos y Sedantes , Ketamina , Humanos , Dexmedetomidina/administración & dosificación , Ketamina/administración & dosificación , Masculino , Femenino , Preescolar , Hipnóticos y Sedantes/administración & dosificación , Ansiedad al Tratamiento Odontológico/prevención & control , Resultado del Tratamiento , Conducta Infantil/efectos de los fármacos , Estadísticas no Paramétricas , Factores de Tiempo , Hemodinámica/efectos de los fármacos , Atención Dental para Niños/métodos , Anestesia Dental/métodos , Reproducibilidad de los Resultados , Saliva/química , Combinación de Medicamentos , Valores de ReferenciaRESUMEN
INTRODUCTION: The need for safe anesthetic agents with minimal side effects has led to the development of remimazolam, a new benzodiazepine designed to be an alternative to the commonly used drug propofol, which has significant hemodynamic effects. This study aims to compare the hemodynamic effects of remimazolam with propofol during general anesthesia. EVIDENCE ACQUISITION: A systematic search was conducted in Embase, Web of Science, Cochrane Library, Scopus, and PubMed databases on 13/02/2023, following the recommendations of Cochrane Handbook and the PRISMA statement. The measure of association used was Risk Ratio (RR) or standardized mean difference, with 95% confidence intervals (CI) and 95% Prediction intervals (PI). An additional search was conducted on 04/09/2023. A Trial Sequential Analysis and a GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence table were conducted based on the editor's recommendation. EVIDENCE SYNTHESIS: After applying eligibility criteria and removing duplicates, 16 randomized clinical trials comprising 1951 patients were included in the meta-analysis. Significant associations favoring remimazolam over propofol were observed in the following aspects: intraoperative hypotension events (RR=0.47; 95% CI=0.41 to 0.54; 95% PI=0.40 to 0.55); frequency of vasoactive drug administration (RR=0.54; 95% CI=0.46 to 0.64; 95% PI=0.41 to 0.74); intraoperative bradycardia (RR=0.39; 95% CI=0.27 to 0.57; 95% PI=0.26 to 0.66); mean arterial pressure at induction (MD=7.77; 95% CI=6.00 to 9.55; 95% PI=4.39 to 11.15); heart rate at induction (MD=6.40; 95% CI=4.07 to 8.73; 95% PI=0.33 to 12.48); and heart rate at intubation (MD=6.06; 95% CI=2.33 to 9.78; 95% PI=-5.59 to 17.71). CONCLUSIONS: This study provides evidence that remimazolam induces fewer cardiorespiratory depressant effects and has a more favorable side effect profile compared to propofol during general anaesthesia.
Asunto(s)
Anestesia General , Benzodiazepinas , Hemodinámica , Propofol , Humanos , Anestesia General/efectos adversos , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Hemodinámica/efectos de los fármacos , Propofol/administración & dosificación , Propofol/efectos adversosRESUMEN
OBJECTIVE: The use of vasopressin as an adjunctive therapy in pulmonary hypertension associated with refractory systemic hypotension has increased. The objective of our study is to describe its effects on term infants. STUDY DESIGN: Retrospective observational study. Setting in a referral level IV neonatal intensive care unit from a middle-income region. The patients are term neonates admitted to our NICU who required vasopressin due to severe Pulmonary Hypertension and refractory hypotension during a 49-month period (December 2019 and December 2023). RESULTS: We identified 68 term infants, all in mechanical ventilation, receiving inhaled nitric oxide (iNO), and a phased protocol management for hypotension. Vasopressin was a started at a mean of 2 days with a mean duration of 80 h. Regarding hemodynamic outcome: diastolic, systolic, and median systemic pressure significantly increased during the first 4 h of treatment, as well as arterial pH and urine output. Accordingly, lactate and Vasoactive Inotropic Score (VIS) score decreased after 4 and 8 h, respectively, after vasopressin was started. Regarding oxygenation markers: oxygen requirements and mean airway pressure decreased significantly (and therefore the oxygenation index decreased in concordance) after 4 h of vasopressin. Echocardiographic indices of pulmonary hypertension progressively improved after vasopressin infusion with a significant decrease of tricuspid ingurgitation velocities and the rate of right-to- left ductal shunt through the ductus arteriosus. In the same way, left and right ventricular output increased after the initiation of vasopressin. CONCLUSION: This study showed that the use of vasopressin in neonates with persistent pulmonary hypertension was associated with a rapid and significant improvement in oxygenation and hemodynamic markers of perfusion, including blood pressure. Its effects begin early during the first hours of treatment.
Asunto(s)
Hipertensión Pulmonar , Hipotensión , Vasopresinas , Humanos , Recién Nacido , Estudios Retrospectivos , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Femenino , Masculino , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Vasopresinas/uso terapéutico , Vasopresinas/administración & dosificación , Vasoconstrictores/uso terapéutico , Vasoconstrictores/administración & dosificación , Óxido Nítrico/administración & dosificación , Respiración Artificial , Unidades de Cuidado Intensivo Neonatal , Ecocardiografía , Hemodinámica/efectos de los fármacosRESUMEN
The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.
Asunto(s)
Cardiotónicos , Dobutamina , Choque Séptico , Humanos , Gasto Cardíaco/efectos de los fármacos , Cardiotónicos/uso terapéutico , Cardiotónicos/farmacología , Dobutamina/uso terapéutico , Dobutamina/farmacología , Hemodinámica/efectos de los fármacos , Choque Séptico/tratamiento farmacológico , Choque Séptico/fisiopatología , AnimalesRESUMEN
Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.
Asunto(s)
Isoflurano , Metaloproteinasa 2 de la Matriz , Óxido Nítrico , Vasodilatación , Animales , Femenino , Embarazo , Ratas , Anestésicos por Inhalación/farmacología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Hemodinámica/efectos de los fármacos , Isoflurano/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Óxido Nítrico/metabolismo , Vasodilatación/efectos de los fármacos , Ratas WistarRESUMEN
BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.
FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.
Asunto(s)
Sistema Nervioso Autónomo , Colecalciferol , Suplementos Dietéticos , Frecuencia Cardíaca , Hemodinámica , Obesidad , Sobrepeso , Vitamina D , Humanos , Persona de Mediana Edad , Masculino , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiopatología , Femenino , Método Doble Ciego , Adulto , Hemodinámica/efectos de los fármacos , Estudios Prospectivos , Obesidad/fisiopatología , Obesidad/complicaciones , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Anciano , Colecalciferol/administración & dosificación , Sobrepeso/fisiopatología , Sobrepeso/complicaciones , Vitamina D/sangre , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Resultado del Tratamiento , Deficiencia de Vitamina D/fisiopatología , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/complicaciones , Índice de Masa Corporal , Vitaminas/administración & dosificación , Vitaminas/uso terapéutico , Factores de Tiempo , Valores de Referencia , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: In our study, we aimed to compare the effect of standard rapid sequence intubation protocol and the application of rocuronium priming technique on the procedure time and hemodynamic profile. METHODS: Patients who applied to the emergency department and needed rapid sequence intubation were included in our study, which we conducted with a randomized controlled design. Randomization in the study was made according to the order of arrival of the cases. Rapid sequence intubation was performed in the standard group. In the priming group, 10% of the rocuronium dose was administered approximately 3 min before the induction agent. Intubation time, amount of drug used, vital signs, and end-tidal CO2 level before and after intubation used to confirm intubation were recorded. RESULTS: A total of 52 patients were included in the study, of which 26 patients were included in the standard group and 26 patients in the priming group. While intubation time was 121.2±21.9 s in the standard group, it was calculated as 68.4±11.6 s in the priming group (p<0.001). While the mean arterial pressure was 58.3±26.6 mmHg in the standard group after intubation, it was 80.6±21.1 mmHg in the priming group (p=0.002). CONCLUSION: It was observed that priming with rocuronium shortened the intubation time and preserved the hemodynamic profile better. CLINICAL TRIAL REGISTRATION NUMBER: NCT05343702.
Asunto(s)
Androstanoles , Servicio de Urgencia en Hospital , Intubación Intratraqueal , Fármacos Neuromusculares no Despolarizantes , Intubación e Inducción de Secuencia Rápida , Rocuronio , Humanos , Rocuronio/administración & dosificación , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Femenino , Masculino , Intubación e Inducción de Secuencia Rápida/métodos , Adulto , Persona de Mediana Edad , Androstanoles/administración & dosificación , Factores de Tiempo , Intubación Intratraqueal/métodos , Hemodinámica/efectos de los fármacosRESUMEN
OBJECTIVES: This study aimed to compare the efficacy of labetalol and lidocaine in tympanoplasty surgery, specifically evaluating their impact on hemodynamic changes and perioperative outcomes. METHODS: A randomized controlled trial was conducted with 64 patients scheduled for tympanoplasty. Patients were randomly assigned to receive either 0.5-2â¯mg/min labetalol or 1.5â¯mg/kg/h lidocaine 1% to achieve controlled hypotension during surgery. The efficacy of the drugs was assessed by comparing the Mean Arterial Pressure (MAP), surgeon's satisfaction, time to target MAP, bleeding volume, postoperative pain scores, the need for analgesic medication in recovery, sedation, and other additional parameters. RESULTS: The hemodynamic parameters showed a similar trend over time in both the labetalol and lidocaine groups. The median bleeding volume in the labetalol group (10 cc) was lower than that in the lidocaine group (30 cc), although this difference was not statistically significant (pâ¯=â¯0.11). Similarly, surgeon's satisfaction level, pain intensity, and sedation level in the recovery room did not show statistically significant differences between the two groups (pâ¯>â¯0.05). The duration of surgery, recovery stay, and extubation time also did not significantly differ between the groups. Both medications took approximately the same time (20â¯min) to reach the target MAP and exhibited comparable hemodynamic responses (pâ¯>â¯0.05). CONCLUSION: Both labetalol and lidocaine effectively achieved controlled hypotension during tympanoplasty surgery, thereby improving surgical conditions. The choice of medication should be based on individual patient characteristics and the anesthesiologist's judgment. LEVEL OF EVIDENCE: II.
Asunto(s)
Anestésicos Locales , Hipotensión Controlada , Labetalol , Lidocaína , Timpanoplastia , Humanos , Lidocaína/administración & dosificación , Lidocaína/uso terapéutico , Femenino , Masculino , Labetalol/uso terapéutico , Labetalol/administración & dosificación , Adulto , Timpanoplastia/métodos , Hipotensión Controlada/métodos , Anestésicos Locales/administración & dosificación , Persona de Mediana Edad , Adulto Joven , Resultado del Tratamiento , Hemodinámica/efectos de los fármacos , Adolescente , Dimensión del DolorRESUMEN
Introducción: aunque las bioprótesis son menos trombogénicas que las válvulas mecánicas; la trombosis de estas es una entidad cada vez más reconocida como causa de disfunción protésica potencialmente reversible. No está definido el beneficio de la anticoagulación rutinaria versus antiagregación plaquetaria luego de la sustitución valvular aórtica (SVA) por bioprótesis. La anticoagulación precoz podría asociarse a menores gradientes transprotésicos con similar riesgo de complicaciones. Objetivos: el objetivo primario es determinar si existe una diferencia significativa en la variación del gradiente transprotésico medio al año de la SVA entre las dos estrategias de tratamiento antitrombótico. Los objetivos secundarios son la comparación de la variación del gradiente máximo y del área valvular aórtica, y parámetros clínicos que incluyen la Clase Funcional de la New York Heart Association, las tasas de sangrado mayor y menor y la incidencia de eventos embólicos. Este trabajo representa el análisis interino a 3 meses de un proyecto a más largo plazo, y se propone mostrar los resultados preliminares de los puntos finales previamente definidos. Métodos: se presenta el análisis interino de un ensayo randomizado multicéntrico. Todos los pacientes sometidos a SVA por bioprótesis porcinas fueron sucesivamente reclutados en dos centros de cirugía cardíaca desde el 01/01/2019 hasta el 01/09/2019. El grupo anticoagulación recibió warfarina durante los primeros 3 meses y ambos recibieron aspirina a largo plazo. Se realizaron instancias de seguimiento clínicas y ecocardiográficas antes del alta, a los 3 meses y al año. Resultados: se reclutaron 107 pacientes; 46% de ellos fueron randomizados al grupo anticoagulación y 54% al grupo control. No existieron diferencias en las características basales. Tampoco existieron diferencias significativas entre ambos grupos en la variación entre el alta y los 3 meses del área valvular protésica, coeficiente de obstrucción, gradiente máximo ni gradiente medio ni en la clase funcional. En cuanto a las complicaciones, no existieron eventos embólicos y los sangrados no difirieron significativamente entre ambos grupos. Conclusiones: la anticoagulación no modificó la variación de los gradientes transprotésicos a los 3 meses. Asimismo, no produjo mayor incidencia de efectos adversos. Todavía no está dilucidado si la anticoagulación precoz con warfarina luego de la SVA tiene impacto en los resultados a largo plazo.
Introduction: although bioprostheses are less thrombogenic than mechanical valves, bioprosthesis valve thrombosis is an increasingly recognized entity that can cause potentially reversible prosthetic valve dysfunction. There is a lack of consensus whether to use anticoagulation after aortic valve replacement (AVR) or antiplatelet therapy. Our hypothesis is that early anticoagulation is associated with lower transprosthetic gradients with similar risk of complications. Objective: primary objective is to determine if there is a significant difference in the variation of the mean transprosthetic gradient (ΔGm) one year after SVA between the two antithrombotic treatment strategies. Secondary objectives are the comparison of the variation of maximum gradient and aortic valve area, and clinical parameters including NYHA functional class, major and minor bleeding rates, and the incidence of embolic events. This work represents the 3-month interim analysis of a longer-term project, and is intended to show the preliminary results of the previously defined end points. Methods: this is an interim analysis of a multicenter randomized trial. All patients who underwent AVR by porcine bioprostheses were successively recruited in two cardiac surgery centers in Montevideo between 01/01/2019 and 01/09/2019. The anticoagulation group received warfarin for 3 months. Both groups received aspirin. Clinical and echocardiographic follow-up consultations were performed before discharge, at 3 months, and at 1 year. Results: 107 patients were recruited, 46% were randomized to the anticoagulation group and 54% to the control group. There were no differences in baseline characteristics. There were no significant differences between the two groups in the variation between discharge and 3 months of effective orifice area, doppler velocity index, peak gradient and mean gradient. There were also no differences between both groups in functional class. Regarding complications, there were no embolic events and bleeding did not differ significantly. Conclusions: in this study, anticoagulation did not modify the variation of transprosthetic gradients at 3 months. Likewise, it did not produce a higher incidence of adverse effects. It remains unclear whether early anticoagulation with warfarin after AVR has an impact on long-term outcomes.
Introdução: embora as biopróteses sejam menos trombogênicas que as mecânicas, a trombose de biopróteses é uma entidade cada vez mais reconhecida como causa de disfunção protética potencialmente reversível. A anticoagulação de rotina após a substituição da valva aórtica por bioprótese (SVA) não está definida. Nossa hipótese é que a anticoagulação precoce está associada a menores gradientes transprotéticos com risco semelhante de complicações. Objetivo: o objetivo principal é determinar se há uma diferença significativa na variação do gradiente transprotético médio (ΔGm) um ano após SVA entre as duas estratégias de tratamento antitrombótico. Os objetivos secundários são a comparação da variação do gradiente máximo e da área valvar aórtica e parâmetros clínicos, incluindo NYHA CF, taxas de sangramento maior e menor e incidência de eventos embólicos. Este trabalho representa a análise intercalar de 3 meses de um projeto de longo prazo, e pretende mostrar os resultados preliminares dos pontos finais previamente definidos. Métodos: apresenta-se a análise interina de um estudo multicêntrico randomizado. Todos os pacientes submetidos a SVA por biopróteses suínas foram sucessivamente recrutados em dois centros de cirurgia cardíaca em Montevidéu, durante um período de recrutamento de 1/1/2019 a 1/9/2019. O grupo de anticoagulação recebeu warfarina por 3 meses. Ambos os grupos receberam aspirina. Foram realizadas consultas médicas clínicas e ecocardiográficas antes da alta, aos 3 meses e ao 1 ano. Resultados: foram recrutados 107 pacientes, 46% foram randomizados para o grupo anticoagulação e 54% para o grupo controle. Não houve diferenças nas características basais. Não houve diferenças significativas entre os dois grupos da variação entre alta e 3 meses na área valvar, coeficiente de obstrução, gradiente máximo ou gradiente médio. Também não houve diferenças entre os dois grupos na classe funcional. Em relação às complicações, não houve eventos embólicos e sangramentos não diferiram significativamente. Conclusões: neste estudo, a anticoagulação não modificou a variação dos gradientes transprotéticos aos 3 meses. Da mesma forma, não produziu maior incidência de efeitos adversos. Ainda não está claro se a anticoagulação precoce com varfarina após SVA tem impacto nos resultados a longo prazo.
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Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Warfarina/administración & dosificación , Warfarina/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Bioprótesis , Prótesis Valvulares Cardíacas , Estudios Prospectivos , Estudio Multicéntrico , Ensayo Clínico Controlado Aleatorio , Octogenarios , Hemodinámica/efectos de los fármacosRESUMEN
SUMMARY: To observe the effect of sevoflurane combined with brachial plexus block (BPB) in children with humeral fracture surgery and its effect on hemodynamics. 84 children who received surgical treatment of humeral fracture in our hospital from September 2019 to September 2022 were selected. According to different anesthesia methods, the children were divided into control group and study group. The control group only received laryngeal mask sevoflurane; the study group received laryngeal mask sevoflurane combined with BPB. The operation situation, hemodynamic indexes, stress level, pain and adverse reactions of children was observed. The postoperative awakening time in the study group was lower than control group, the postoperative pain onset time in the study group was higher than control group (P0.05). Postoperative 2h, the levels of serum cortisol, b-endorpin, norepinephrine and epinephrine in the study group were lower than control group (P0.05). Sevoflurane combined with BPB is helpful to shorten the postoperative awakening time of children with humeral fracture, reduce the degree of postoperative pain, improve hemodynamics, and reduce stress response, and has good safety.
El objetivo fue observar el efecto del sevoflurano combinado con bloqueo del plexo braquial (BPB) en niños con cirugía de fractura de húmero y su efecto sobre la hemodinámica. Se seleccionaron 84 niños que recibieron tratamiento quirúrgico de fractura de húmero en nuestro hospital desde septiembre de 2019 hasta septiembre de 2022. Según diferentes métodos de anestesia, los niños se dividieron en grupo control y grupo de estudio. El grupo control solo recibió sevoflurano en mascarilla laríngea; el grupo de estudio recibió sevoflurano con mascarilla laríngea combinado con BPB. Se observó la situación operatoria, índices hemodinámicos, nivel de estrés, dolor y reacciones adversas de los niños. El tiempo hasta el despertar postoperatorio en el grupo de estudio fue menor que el del grupo control, el tiempo de aparición del dolor postoperatorio en el grupo de estudio fue mayor que el del grupo control (P0,05). A las 2 horas postoperatorias, los niveles séricos de cortisol, β-endorfina, norepinefrina y epinefrina en el grupo de estudio fueron más bajos que los del grupo control (P 0,05). El sevoflurano combinado con BPB es útil para acortar el tiempo de despertar del posoperatorio de los niños con fractura de húmero, reduce el grado de dolor postoperatorio, mejora la hemodinámica y reduce la respuesta al estrés, además de tener buena seguridad.
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Humanos , Masculino , Femenino , Niño , Bloqueo del Plexo Braquial , Sevoflurano/administración & dosificación , Fracturas del Húmero/cirugía , Anestésicos por Inhalación , Hemodinámica/efectos de los fármacosRESUMEN
La exodoncia de los terceros molares inferiores es uno de los procedimientos clínicos más comunes en el cual el control del dolor mediante el bloqueo anestésico del nervio alveolar inferior, bucal y lingual resulta ser fundament al y la manera más común de hacerlo es mediante la infiltración de soluciones de anestesia local. Entre ellos la lidocaína y articaína son algunos de los más comunes y pueden estar asociado a vasoconstrictores como la epinefrina que puede provocar aumento de la presión arterial y frecuencia cardíaca razón por la cual se hace necesario la monitorización de cambios hemodinámicos durante la cirugía. Describir los cambios hemodinámicos asociados al uso de lidocaína al 2 % y/ o articaína al 4 % en la presión sistólica y diastólica, frecuencia cardiaca y saturación parcial de oxígeno en relación a distintos tiempos operatorios. Se realizó una revisión sistemática en las bases de datos de PubMed, SCOPUS, Web of Science y Sciencedirect. Se analizaron 7 ensayos clínicos controlados en los que utilizaron articaína al 4 % y/o lidocaína al 2 % con epinefrina al 1:100,000 y/o 1:200,000 en volúmenes de 1,8 a 5,4 mL, en los cuales evaluaron la presión sistólica y diastólica, frecuencia cardiaca y saturación parcial de oxígeno en distintos tiempos de la cirugía. Si bien hubo cambios en PAS, PAD, FC y SPO2, todas se mantuvieron dentro de rangos normales bajo el uso de articaína al 4 % y lidocaína al 2 % con epinefrina 1:100,000 y/o 1:200,000 a volúmenes de 1,8 a 5,4mL medidas a distintos tiempos operatorios.
The extraction of lower third molars is one of the most common clinical procedures in which pain control through anesthetic blockade of the lower alveolar, buccal and lingual nerves turns out to be essential and the most common way to do it is through the infiltration of solutions of local anesthesia. Among them, lidocaine and articaine are some of the most common and may be associated with vasoconstrictors such as epinephrine, which can cause an increase in blood pressure and heart rate, which is why it is necessary to monitor hemodynamic changes during surgery. To describe the hemodynamic changes associated with the use of 2 % lidocaine and/or 4 % articaine in systolic and diastolic pressure, heart rate and partial oxygen saturation in relation to different operative times. A systematic review was carried out in the PubMed, SCOPUS, Web of Science and Sciencedirect databases. Seven controlled clinical trials were analyzed in which 4 % articaine and/or 2 % lidocaine were used with epinephrine at 1:100,000 and/or 1:200,000 in volumes of 1,8 to 5,4 mL, in which systolic pressure was evaluated. and diastolic, heart rate and partial oxygen saturation at different times of surgery. Although there were changes in SBP, DBP, HR and SPO2, all remained within normal ranges under the use of 4 % articaine and 2 % lidocaine with epinephrine 1:100,000 and/or 1:200,000 at volumes of 1,8 to 5 .4mL measured at different operative times.
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Humanos , Masculino , Femenino , Carticaína/uso terapéutico , Monitorización Hemodinámica/métodos , Anestésicos Locales/uso terapéutico , Lidocaína/uso terapéutico , Tercer Molar/cirugía , Cirugía Bucal , Hemodinámica/efectos de los fármacosRESUMEN
The aim of this systematic review is to assess the safety of local anaesthetics (LA) combined with vasoconstrictors (VC) for patients with controlled hypertension undergoing dental procedures. A comprehensive search strategy were used to identify all relevant randomized controlled trials (RCTs) that evaluated the effect of LA combined with VC. All searches covered the period from 1990 to February 2021. We performed a meta-analysis using random-effect models and assessed overall certainty in evidence using GRADE approach. Our search strategy yielded 1262 references. Finally, seven randomised trials were included, but only three were included in the meta-analysis. The use of LA with VC may result in little to no difference in the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), but the certainty of the evidence was assessed as low. Death, stroke, acute myocardial infarction, need for hospitalization, pain and bleeding were not reported by the included studies. The hemodynamic changes using VC do not imply an increased risk of occurrence of adverse cardiovascular events. The use of VC could even be recommendable considering their multiple advantages.
El objetivo de esta revisión sistemática es evaluar la seguridad del uso de anestésicos locales (AL) combinados con vasoconstrictor (VC) en pacientes con hipertensión controlada durante procedimientos dentales. Se realizó una estrategia de búsqueda para identificar todos los estudios clínicos aleatorizados (ECA) relevantes que evaluaban el efecto del AL combinado con VC. Todos los estudios fueron del periodo entre 1990 a febrero del 2021. Se realizó un meta-análisis usando modelos de efecto aleatorizado y una revisión de la certeza de la evidencia usando el método GRADE. Nuestra estrategia de búsqueda arrojó 1262 referencias. Finalmente, siete estudios clínicos aleatorizados fueron incluidos, de los cuales tres fueron incluidos en el meta-análisis. El uso de AL con VC produce una pequeña a ninguna diferencia en el pulso cardiaco, presión sistólica y diastólica, pero la certeza de la evidencia fue baja. Muerte, infarto agudo al miocardio, accidente cerebrovascular, necesidad de hospitalización, dolor y hemorragia no fueron reportados en los estudios incluidos. Los cambios hemodinámicos en el uso de VC no implican un aumento de riesgo de ocurrencia de efectos adversos cardiovasculares. El uso de VC puede ser recomendable considerando sus múltiples ventajas.
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Humanos , Atención Odontológica , Hipertensión/cirugía , Anestésicos Locales/uso terapéutico , Vasoconstrictores/uso terapéutico , Hemodinámica/efectos de los fármacosRESUMEN
INTRODUCTION: Septic shock is a lethal disease responsible for a large proportion of deaths in the Intensive Care Unit (ICU), even with therapy centered on fluid resuscitation, use of vasopressors and empirical antibiotic therapy applied within the first hour of diagnosis. Considering the multifactorial pathophysiology of septic shock and the mechanism of action of vasopressors, some patients may not respond adequately, which can lead to the maintenance of vasodilatation, hypotension and increased morbidity, and mortality. This protocol aims to verify whether the use of methylene blue in septic patients with an early diagnosis can contribute to an earlier resolution of a shock compared to standard treatment. METHODS AND ANALYSIS: This is a study protocol for a single-center randomized clinical trial design in an ICU of a tertiary university hospital. In this study, we intend to include 64 patients aged between 18 and 80 years with a diagnosis of septic shock, of any etiology, with up to 72âhours of evolution after volume restoration, using norepinephrine at a dose ≥0.2âµg/kg/min and vasopressin at a dose of 0.04âIU/min. After the initial approach, we will randomize patients into two groups, standard care, and standard care plus methylene blue. The sample size was calculated in order to show 30% differences in septic shock resolution between groups. The Research Ethics Committee approved the study, and all patients included will sign an informed consent form (Clinical registration: RBR-96584w4).
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Hemodinámica , Hipotensión , Choque Séptico/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Hemodinámica/efectos de los fármacos , Humanos , Hipotensión/tratamiento farmacológico , Azul de Metileno/administración & dosificación , Azul de Metileno/uso terapéutico , Persona de Mediana Edad , Norepinefrina , Ensayos Clínicos Controlados Aleatorios como Asunto , Choque Séptico/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS: Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS: L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION: L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.
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Arginina/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Antebrazo/irrigación sanguínea , Hemodinámica/efectos de los fármacos , Microcirculación/efectos de los fármacos , Uñas/irrigación sanguínea , Administración Oral , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Presión Arterial/efectos de los fármacos , Biomarcadores/sangre , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Angioscopía Microscópica , Pletismografía , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Vasodilatación/efectos de los fármacos , Adulto JovenRESUMEN
ABSTRACT: Paracetamol (PAR) is the most common over-the-counter drug recommended by physicians for treatment of pain and fever during gestation. This drug is not teratogenic, being considered safe for fetus; however, PAR crosses the blood-placental barrier. Considering that, the present study aimed to evaluate the vascular and metabolic safety of PAR exposure during intrauterine and neonatal development in adult male and female-exposed offspring. Wistar female rats were gavaged, with PAR (350 mg/kg/d), from gestational day 6-21 or from gestational day 6 until postnatal day 21. Control dams received water by gavage at the same periods. The male and female offspring were evaluated at adulthood (80 days of life). The thoracic aorta reactivity to acetylcholine, sodium nitroprusside, and phenylephrine was evaluated in male and female adult offspring. It was observed that aortic relaxation was similar between the PAR and control offspring. In addition, the contraction to phenylephrine was similar between the groups. Further, the insulin sensitivity, adipose tissue deposition and blood pressure were not different between PAR and control adult offspring. These results suggest that the protocol of PAR exposure used in the present study did not program vascular and metabolic alterations that would contribute to the development of cardiometabolic diseases in adult life, being safe for the exposed offspring.
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Acetaminofén/toxicidad , Analgésicos no Narcóticos/toxicidad , Enfermedades Cardiovasculares/inducido químicamente , Lactancia , Enfermedades Metabólicas/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Adiposidad/efectos de los fármacos , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Femenino , Edad Gestacional , Hemodinámica/efectos de los fármacos , Resistencia a la Insulina , Masculino , Enfermedades Metabólicas/sangre , Enfermedades Metabólicas/fisiopatología , Embarazo , Ratas Wistar , Medición de RiesgoRESUMEN
The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3+ and CD4+ lymphocytes, and CD68+ and CD206+ macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4+ lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.
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Presión Sanguínea/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Corazón/efectos de los fármacos , Infarto del Miocardio/fisiopatología , Bromuro de Piridostigmina/farmacología , Bazo/efectos de los fármacos , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiopatología , Corazón/fisiopatología , Hemodinámica/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas SHR , Bazo/fisiopatologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Aloysia polystachya (Griseb) Moldenke (Verbenaceae), popularly known as "burrito", is a South American species widely prescribed by local Brazilian healers for the treatment of cardiovascular diseases. However, its antihypertensive and cardioprotective effects are still unknown. AIM: To evaluate the role of the ethanol-soluble fraction of A. polystachya leaves (ESAP) against hypertension in spontaneously hypertensive rats (SHRs), as well as its safety, morphoanatomical and phytochemical aspects. MATERIALS AND METHODS: First, the leaves and stems of A. polystachya were analyzed by optical and scanning electron microscopy in order to provide anatomical data for quality control. Then, ESAP was obtained and its chemical profile was analyzed by LC-DAD-MS. In addition, the cytotoxic and acute toxicity potential of ESAP were evaluated in six cell lines and in female Wistar rats, respectively. Next, female spontaneously hypertensive rats (SHRs) received ESAP (30, 100, 300 mg/kg), hydrochlorothiazide (25 mg/kg), or vehicle once daily for 28 days. Weekly kidney function was monitored by analyzing urinary parameters. At the end of the 28-day treatment, the electrocardiographic profile, blood pressure, and renal and mesenteric vascular reactivity were evaluated. Relative organ (heart, kidney, and liver) weights and biochemical parameters were also evaluated. Finally, the heart, kidneys, and aorta were collected for determination of the tissue redox state, cardiac morphometry, and histopathological analysis. RESULTS: The chemical profile of ESAP was composed by organic acids, a nucleoside, methoxylated flavones and glycosylated compounds including phenolic acids, phenylpropanoids, iridoids and monoterpenes. No signs of toxicity were observed in all cell's lines nor in female Wistar rats submitted to this trial. All SHRs from the negative control group presented a reduction in renal function, alterations in the renal and mesenteric vascular reactivity, and electrocardiographic and morphometric changes typical of ventricular hypertrophy. Oral prolonged ESAP-administration in SHRs was able to reverse renal, electrocardiographic and hemodynamic changes induced by hypertension. Moreover, ESAP-treatment was able to modulate the vascular and renal arterial reactivity and tissue redox state. The aforementioned data were accompanied by reduction of cardiac hypertrophy. CONCLUSION: In this study, we present important anatomical and phytochemical data that contributed to the correct identification and quality control of A. polystachya. In addition, we have shown that ESAP is safe after acute administration and present significant cardioprotective effects (at 30, 100, and 300 mg/kg doses) in SHRs after prolonged treatment.
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Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Verbenaceae , Animales , Antihipertensivos/química , Antihipertensivos/toxicidad , Presión Sanguínea/efectos de los fármacos , Brasil , Línea Celular , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Etanol/química , Etnofarmacología , Femenino , Corazón/efectos de los fármacos , Corazón/fisiología , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Riñón/efectos de los fármacos , Riñón/fisiología , Hígado/efectos de los fármacos , Hígado/patología , Miocardio/patología , Fitoquímicos/análisis , Fitoquímicos/uso terapéutico , Fitoquímicos/toxicidad , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Solventes/químicaRESUMEN
AIMS: We examined the effects of treatment with 1-nitro-2-phenylethane (NP), a novel soluble guanylate cyclase stimulator, on monocrotaline (MCT)-induced PAH in rats. MAIN METHODS: At day 0, male adult rats were injected with a single subcutaneous (s.c.) dose of monocrotaline (60 mg/kg). Control (CNT) rats received an equal volume of monocrotaline's vehicle only (s.c.). Four weeks later, MCT-treated rats were treated orally for 14 days with NP (50 mg/kg/day) (MCT-NP group) or its vehicle (Tween 2%) (MCT-V group). At the end of the treatment period and before invasive hemodynamic study, rats of all experimental groups were examined by echocardiography. KEY FINDINGS: With respect to CNT rats, MCT-V rats showed significant; (1) increases in pulmonary artery (PA) diameter, RV free wall thickness and end-diastolic RV area, and increase of Fulton index; (2) decreases in maximum pulmonary flow velocity, PA acceleration time (PAAT), PAAT/time of ejection ratio, and velocity-time integral; (3) increases in estimated mean pulmonary arterial pressure; (4) reduction of maximal relaxation to acetylcholine in aortic rings, and (5) increases in wall thickness of pulmonary arterioles. All these measured parameters were significantly reduced or even abolished by oral treatment with NP. SIGNIFICANCE: NP reversed endothelial dysfunction and pulmonary vascular remodeling, which in turn reduced ventricular hypertrophy. NP reduced pulmonary artery stiffness, normalized the pulmonary artery diameter and alleviated RV enlargement. Thus, NP may represent a new therapeutic or a complementary approach to treatment of PAH.