Efeito da nitroglicerina no espasmo e na oclusão da artéria radial em cateterismos transradiais realizados em mulheres / Effect of nitroglycerin on radial artery spasm and occlusion in transradial catheterizations performed in women

Introdução: O benefício do cateterismo transradial já foi confirmado em pacientes do sexo feminino. Mulheres submetidas a exames por cateterismo transradial apresentam desafios únicos. A ocorrência de espasmo e oclusão da artéria radial após o procedimento é maior em mulheres. Objetivamos avaliar o benefício da nitroglicerina na redução de espasmo e oclusão da artéria radial em mulheres submetidas a cateterismo transradial. Métodos: Estudo multicêntrico, prospectivo, randomizado 2x2 fatorial, duplo-cego. Participantes foram randomizados para nitroglicerina 500mcg ou placebo em dois momentos: após colocação do introdutor hemostático e antes da retirada. A avaliação de espasmo da artéria radial foi clínica, por meio de escala dor. A avaliação da oclusão da artéria radial foi realizada com Doppler, nas primeiras 12 horas. Resultados: Foram incluídos 2.040 pacientes, sendo 774 (37,5%) mulheres. A média de idade foi similar entre os sexos (62,2 anos versus 61,5 anos; p=0,27). A incidência de espasmo da artéria radial foi maior nas mulheres (21,2% versus 6,6%; p<0,01), bem como a incidência de oclusão da artéria radial (3,4% versus 1,8%; p=0,03). O uso da nitroglicerina no início do procedimento não reduziu a incidência de espasmo da artéria radial em mulheres quando comparado com o placebo (19,7% versus 22,6%; p=0,34), tampouco as taxas de oclusão da artéria radial (4,3% versus 2,5%; p=0,17). O uso da nitroglicerina ao fim do procedimento não reduziu a incidência de oclusão da artéria em mulheres (2,8% versus 3,9%; p=0,37). Conclusões: O espasmo e a oclusão da artéria radial são mais frequentes em mulheres submetidas a cateterismo transradial quando comparadas aos homens. O uso da nitroglicerina não apresenta efeito benéfico na redução dessas incidências.

Background: The benefit of transradial catheterization is well established in female patients. Women undergoing transradial catheterization exams present with unique challenges. The occurrence of radial artery spasm and occlusion after the procedure is higher in women. The objective of this study was to evaluate the benefit of nitroglycerin in reducing radial artery spasm and occlusion in women undergoing transradial catheterization. Methods: This was a 2x2 factorial randomized, multicenter, prospective, double-blinded study. Participants were randomized to nitroglycerin 500mcg or placebo at two time points: after placement of the hemostatic introducer and before its removal. The evaluation of the radial artery spasm was clinical, using a pain scale The evaluation of the radial artery occlusion was performed with Doppler, in the first 12 hours. Results: A total of 2,040 patients were included, of which 774 (37.5%) were female. Mean age was similar between sexes (62.2 years versus 61.5 years; p=0.27). The incidence of radial artery spasm was higher in women (21.2% versus 6.6%; p<0.01), as well as the incidence of radial artery occlusion (3.4% versus 1.8%; p=0.03). The use of nitroglycerin at the beginning of the procedure did not reduce the incidence of radial artery spasm in women when compared with placebo (19.7% versus 22.6%; p=0.34), nor did the rates of radial artery occlusion (4.3% versus 2.5%; p=0.17). The use of nitroglycerin at the end of the procedure did not reduce the incidence of artery occlusion in women (2.8% versus 3.9%; p=0.37). Conclusions: Radial artery spasm and occlusion are more frequent in women undergoing transradial catheterization when compared to men. The use of nitroglycerin does not have a beneficial effect in reducing these incidences.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension / Perda de resposta a bloqueadores dos canais de cálcio após acompanhamento prolongado em pacientes com hipertensão arterial pulmonar idiopática

ABSTRACT Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

RESUMO Pacientes com hipertensão arterial pulmonar (HAP) idiopática com resposta positiva ao teste de vasorreatividade aguda e resposta clínica a bloqueadores dos canais de cálcio (BCC) durante no mínimo um ano são tradicionalmente denominados "respondedores verdadeiros". No entanto, pouco se sabe sobre a manutenção da resposta a BCC durante períodos mais longos. Avaliamos a perda de resposta a BCC após tratamento prolongado em uma coorte de pacientes com HAP idiopática previamente considerados respondedores verdadeiros. Nossos dados sugerem que pacientes com HAP idiopática podem deixar de apresentar resposta clínica a BCC mesmo depois de um ano de estabilidade clínica, reforçando a necessidade de reavaliação multidimensional constante para avaliar a necessidade de terapias específicas para HAP e classificar esses pacientes corretamente.

Insuficiencia Cardíaca Aguda / Acute Heart Failure

En el mundo actual las perspectivas de abordaje, y las estrategias terapéuticas en cuanto a pacientes que se presenten con Insuficiencia Cardiaca (IC) de reciente diagnóstico "de novo", o que presentan una descompensación de su patología, han tenido un avance claro dándonos una gran diversidad de opciones terapéuticas para el cuidado y acompañamiento de dicha patología; así como en la perspectiva de un seguimiento crónico, no solo cardiológico, sino que se ha convertido en un verdadero desafío multidisciplinario, en busca de la mejor opción terapéutica y concluir con el cuidado paliativo de nuestro paciente.

In the current world, the perspectives of approach, and the therapeutic strategies regarding patients who present with Heart Failure (HF) of recent diagnosis "de novo", or who present a decompensation of their pathology, have had a clear advance giving us a great diversity of therapeutic options for the care and accompaniment of said pathology; as well as in the perspective of chronic follow-up, not only cardiological, but it has become a true multidisciplinary challenge, looking for the best therapeutic option and concluding with the palliative care of our patient.

Effect of papaverine on left internal mammary artery flow: topical spraying versus perivascular injection method

Abstract Objective: To analyze two techniques of papaverine application, topical spray on the harvested left internal mammary artery (LIMA) and perivascular injection, to find out their ability to improve LIMA flow. Methods: Forty patients were randomized into two groups. In Group 1, papaverine was sprayed on the harvested pedunculated LIMA. In Group 2, papaverine was delivered into the perivascular plane. Drug dosage was the same for both groups. LIMA flow was measured 20 minutes after applying papaverine. Blood flow was recorded for 20 seconds and flow per minute was calculated. The systemic mean pressures were maintained at 70 mmHg during blood collection. The data collected was statistically evaluated and interpreted. Results: The LIMA blood flow before papaverine application in the Group 1 was 51.9±13.40 ml/min and in Group 2 it was 55.1±15.70 ml/min. Statistically, LIMA flows were identical in both groups before papaverine application. The LIMA blood flow, post papaverine application, in Group 1 was 87.20±13.46 ml/min and in Group 2 it was 104.7±20.19 ml/min. The Group 2 flows were statistically higher than Group 1 flows. Conclusion: Papaverine delivery to LIMA by the perivascular injection method provided statistically significant higher flows when compared to the topical spray method. Hence, the perivascular delivery of papaverine is more efficient than the spray method in improving LIMA blood flow.

The Clinical Efficacy of Pulmonary Hypertension-Specific Agents in Idiopathic Pulmonary Fibrosis: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

BACKGROUND: Pulmonary hypertension (PH) is common in patients with idiopathic pulmonary fibrosis (IPF) and is associated with poor outcomes. This study was performed to determine the clinical efficacy of PH-specific therapeutic agents for IPF patients.METHODS: We performed a systematic review and meta-analysis using MEDLINE, EMBASE, and the Cochrane Central Register. We searched randomized controlled trials (RCTs) without language restriction until November 2018. The primary outcome was all-cause mortality to end of study.RESULTS: We analyzed 10 RCTs involving 2,124 patients, 1,274 of whom received PH-specific agents. In pooled estimates, the use of PH-specific agents was not significantly associated with reduced all-cause mortality to end of study compared with controls (hazard ratio, 0.99; 95% confidence interval [CI], 0.92, 1.06; P = 0.71; I² = 30%). When we performed subgroup analyses according to the type of PH-specific agent, sample size, age, forced vital capacity, diffusion lung capacity, and the extent of honeycombing, PH-specific agents also showed no significant association with a reduction in all-cause mortality. A small but significant improvement in quality of life, measured using the St. George Respiratory Questionnaire total score, was found in the PH-specific agent group (mean difference, −3.16 points; 95% CI, −5.34, −0.97; P = 0.005; I² = 0%). We found no significant changes from baseline in lung function, dyspnea, or exercise capacity. Serious adverse events were similar between the two groups.CONCLUSION: Although PH-specific agents provided small health-related quality-of-life benefits, our meta-analysis provides insufficient evidence to support their use in IPF patients.

Curcuma Longa Abolishes Phenylephrine-Induced Contractions in Isolated Aortic Artery of Rats

Curcuma longa has biological effects. Its cardiovascular activities are yet to be scientifically studied. Objectives: To investigate the vasorelaxant effects of the aqueous extract of Curcuma longa (AECL). Methods: Aortic annuli of normotensive rats, with or without endothelium, were set up in a data storage system with nutrient solution in recipients, with scientifically recommended temperature, aeration and tension. Over contraction by Phenylephrine, the AECL (1, 3, 10, 30, 100, 300 and 1000 µg/mL) was incubated before and after incubation with atropine or L-name or indomethacin. An AECL concentration-response curve was also built over contractions caused by elevation of extracellular K+. Data were significant when p < 0.05, with GraphPad Prism 6.0 software resolutions. Results: The AECL induced 100% vasorelaxation also in the endothelium-free annuli. The part of the endothelium-dependent effect had EC50 = 4.32 ± 0.05 µg/mL. With inhibition of NO production, the EC50 increased to 126.50 ± 2.35 µg/mL; after inhibition of prostacyclin production, to 124.6 ± 0.05 µg/mL; and after muscarinic blockade, to 437.10 ± 0.2 µg/mL. Opening of K+ channels (relaxation of 56.98%) and VOCC blockade (relaxation of 31.56%) were evident. Conclusion: AECL induced significant vasorelaxation, being more significant in the presence of endothelium. The muscarinic pathway seems to be the main one involved in this effect, followed by the NO production and prostacyclin pathways. The activity in K+ channels by AECL was more significant than its VOCC blockade. The use of other models and tools to study action mechanisms will be important and elucidating

Role of Prostaglandins in the Vasodilator Effect of the Aqueous Extract from Artemisia annua Plant in Streptozotocin-induced Diabetic Rats

Aims: One of the most important causes of mortality is vascular complications resulting from diabetes mellitus. Herbal medicines are commonly used for the treatment of cardiovascular conditions in diabetes. Artemisia annua (A. annua) as a medicinal plant has vasculature protective effects in diabetic rats. In the present study, the role of prostaglandins in the vasodilator effect of A. annua aqueous extract in diabetic rats has been studied. Study Design: This animal study was conducted on diabetic rats. Aqueous extract of Artemisia annua was used for diabetic rats. Then, isolated thoracic aortic rings were exposed to indomethacin and after exposure, the contractile responses were measured. Methodology: The studied animals were male Wistar rats (n=36) which were randomly divided into intact, untreated-diabetic, and A. annua aqueous extract treated-diabetic groups. For the induction of diabetes, streptozotocin was intraperitoneally (i.p.) administered (60 mg/kg). A. annua extract-treated group received i.p. 100 mg/kg of extract for one month. After one month, the dose contractile response of isolated aortic rings to phenylephrine (doses of 10-9-10-4 mol/L) in the absence and presence of indomethacin as a prostaglandins inhibitor was determined using isolated tissue setup. Results: Comparison of contractile responses before and after adding indomethacin in treated extract diabetic rats, showed that contractile responses of aorta ring with and without endothelium after adding indomethacin significantly increased at all concentrations of phenylephrine (P<0.05–P<0.0001) while indomethacin in diabetic rats did not effect on contractile response. Conclusions: Since the vasodilator effect of the aqueous extract of A. annua with a concentration of 100 mg/kg of body weight was pronounced even after endothelium removal, it can be claimed that the vasodilator effects of the extract are related to inhibition of prostaglandin generation both indirectly and directly.

Eventos adversos durante transporte intra-hospitalar de pacientes críticos em hospital de grande porte / Adverse events during intrahospital transport of critically ill patients in a large hospital

RESUMO Objetivo: Descrever a incidência de eventos clínicos e não clínicos durante o transporte intra-hospitalar de pacientes críticos e analisar os fatores de risco associados. Métodos: Estudo de coorte, com coleta retrospectiva, no período de outubro de 2016 a outubro de 2017, tendo sido analisados todos os transportes intra-hospitalares para fins diagnósticos e terapêuticos em hospital de grande porte, que contava com seis unidades de terapia intensiva adulto, sendo avaliados os eventos adversos e os fatores de risco relacionados. Resultados: No período, foram realizados 1.559 transportes intra-hospitalares, em 1.348 pacientes, com média de idade de 66 ± 17 anos, tempo médio de transporte de 43 ± 34 minutos. Durante o transporte, 19,8% dos pacientes estavam em uso de drogas vasoativas; 13,7% em uso de sedativos e 10,6% estavam sob ventilação mecânica. Eventos clínicos ocorreram em 117 transportes (7,5%) e não clínicos em 125 transportes (8,0%). Falhas de comunicação foram prevalentes, no entanto, aplicando-se análise multivariada, uso de sedativos, noradrenalina e nitroprussiato, e o tempo de transporte maior que 36,5 minutos estiveram associados a eventos adversos clínicos. Uso de dobutamina e tempo de transporte superior a 36,5 minutos estiveram associados a eventos não clínicos. Ao final do transporte, 98,1% dos pacientes apresentaram condições clínicas inalteradas em relação ao seu estado basal. Conclusão: Transportes intra-hospitalares estão relacionados à alta incidência de eventos adversos; o tempo de transporte e a utilização de sedativos e drogas vasoativas estiveram relacionados a esses eventos.

ABSTRACT Objective: To describe the incidence of clinical and non-clinical events during intrahospital transport of critically ill patients and to analyze the associated risk factors. Methods: Cohort study with retrospective data collected from October 2016 to October 2017. All cases of intrahospital transport for diagnostic and therapeutic purposes in a large hospital with six adult intensive care units were analyzed, and the adverse events and related risk factors were evaluated. Results: During the study period, 1,559 intrahospital transports were performed with 1,348 patients, with a mean age of 66 ± 17 years and a mean transport time of 43 ± 34 minutes. During transport, 19.8% of the patients were using vasoactive drugs; 13.7% were under sedation; and 10.6% were under mechanical ventilation. Clinical events occurred in 117 transports (7.5%), and non-clinical events occurred in 125 (8.0%) transports. Communication failures were prevalent; however, the multivariate analysis showed that the use of sedatives, noradrenaline and nitroprusside and a transport time greater than 36.5 minutes were associated with adverse clinical events. The use of dobutamine and a transport time greater than 36.5 minutes were associated with non-clinical events. At the end of transport, 98.1% of the patients presented unchanged clinical conditions compared with baseline. Conclusion: Intrahospital transport is related to a high incidence of adverse events, and transport time and the use of sedatives and vasoactive drugs were related to these events.

Vasodilatadores: re-visión de un viejo armamento / Vasodilator agents: re-viewing an old weapon

Resumen Los agentes con propiedades vasodilatadoras son un grupo heterogéneo de fármacos que conforman parte del arsenal del cardiólogo desde hace décadas y si bien su prescripción es amplia, no suele ser óptima. El término siempre ha sido ambiguo y propenso a confusión con respecto a los fármacos que deben ser incluidos. Este artículo revisa de manera concisa el estado actual de estos fármacos, incluidos los nuevos agentes desarrollados, con insistencia en sus indicaciones terapéuticas precisas demostradas por evidencia, sus limitaciones y contraindicaciones desde una perspectiva práctica para el cardiólogo clínico. Se realizó una revisión estructurada no sistemática de la bibliografía mediante búsqueda en la base de datos PubMed con el término MeSH: agente vasodilatador. Se incluyeron artículos en español e inglés. Se redactó una revisión narrativa, orientada a una perspectiva clínica, donde se describe el papel actual de los vasodilatadores en la medicina cardiovascular contemporánea. Los vasodilatadores tienen un papel activo y determinante en la cardiología moderna y son una herramienta esencial en diversos escenarios clínicos.

Abstract Agents with vasodilatory properties are a heterogeneous group of drugs that have been part of the arsenal of the cardiologist for decades, and although their use is broad, it is not optimal. The term has always been ambiguous and prone to confusion with respect to the drugs that should be included. This paper makes a concise review of the current state of these drugs including the new agents developed, emphasizing their precise therapeutic uses demonstrated by evidence, its limitations and contraindications from a practical perspective for the clinical cardiologist. A structured, non-systematic review of the literature was performed by searching the PubMed database with the MeSH term: vasodilator agent. Articles in Spanish and English were included. A narrative review was written, oriented to a clinical perspective, which describes the current role of vasodilators in contemporary cardiovascular medicine. Vasodilators have an active and determining role in modern cardiology and are an essential tool in various clinical scenarios.

Milrinona inhalada en hipertensión pulmonar: A propósito de un caso / Case Report: Inhaled milrinone in pulmonary hypertension

INTRODUCCIÓN: Pulmonary hypertension (PH) is a disease that is characterized for an elevated pressure in the pulmonary artery and an increased pulmonary vascular resistance (PVR). Inhaled milrinone has demonstrated acting as a selective pulmonary vasodilator, being a useful tool for the treatment of patients with PH in the perioperative. MATERIALS AND METHODS: We report a successful case of inhaled milrinone in PH in cardiovascular surgery. The patient signed the informed consent for this report. DISCUSSION: Patients with PH has increased risk of perioperative complications (mortality as far as 37-90%) The management with intravenous vasodilators is frequently limited because of secondary effects of vasodilation and hypotension affecting the myocardial perfusion pressure. Milrinone is an inodilator that acts as an inhibitor of the phosphodiesterase III. Wang et al., and posterior studies have demonstrated that administered by inhalation it acts as a selective pulmonary vasodilator and inotrope, with a minor systemic effect. CONCLUSION: Inhaled milrinone have demonstrated to be a useful drug to lower PH, PVR and to enhance inotropism without deleterious systemic effects. Wide availability, lower costs and ease of administration make you think as it could be an ideal tool for perioperative management in patients with PH. There are still more studies to define it´s potentials.

INTRODUCCIÓN: La hipertensión pulmonar (HTP) es una enfermedad caracterizada por la elevación de las presiones de arteria pulmonar (PAP) y un aumento de la resistencia vascular pulmonar (RVP). La milrinona inhalada ha demostrado actuar como un vasodilatador pulmonar selectivo siendo una herramienta útil en el manejo de los pacientes con HTP en el perioperatorio. MATERIALES Y MÉTODOS: Reportamos un caso exitoso de milrinona inhalada en HTP en cirugía cardiovascular. La paciente firmó el consentimiento informado para este reporte. DISCUSIÓN: Pacientes con HTP tienen mayor riesgo de complicaciones perioperatorias (mortalidad hasta 37-90%). Su manejo con vasodilatadores intravenosos es frecuentemente limitado por sus efectos secundarios de vasodilatación e hipotensión, perjudicando la presión de perfusión miocárdica. La milrinona es un inodilatador que actúa como inhibidor de la fosfodiesterasa III. Wang et al., y estudios posteriores, han demostrado que administrada por vía inhalatoria actúa como un vasodilatador pulmonar selectivo e inótropo, con menor efecto sistémico. CONCLUSIÓN: La milrinona inhalada ha demostrado ser una herramienta útil para la disminución de la PAP, RVP y mejoría del inotropismo, sin efectos sistémicos deletéreos. Su amplia disponibilidad, menor costo y facilidad de administración, hacen pensar que podría ser una herramienta útil para el manejo perioperatorio de los pacientes con HTP. Hacen falta más trabajos para definir sus potencialidades.

Advances in pharmacological treatment for acute respiratory distress syndrome / 中国基层医药

Acute respiratory distress syndrome(ARDS) is a common critical syndrome with high morbidity and mortality.The treatments include respiratory support and drug therapy.In this paper, the latest clinical advances in the treatment of ARDS with glucocorticoids, statins, antioxidants, recombinant human activated protein C, sedatives and muscle relaxants, exogenous alveolar surfactants, mesenchymal stem cells, and vasodilators are reviewed.

Progress of inhaled nitric oxide on treatment of persistent pulmonary hypertension of new-born / 中国小儿急救医学

Persistent pulmonary hypertension is a serious disease among new-borns.Despite the variety of causes, similar physiopathologic changes characterize this syndrome: a persistently raised pulmonary vascular resistance after birth, which leads to severe hypoxemia due to extrapulmonary shunting.The fundamental treatment is to reduce pulmonary vascular pressure and improve hemodynamics.Modern treatments such as inhaled nitric oxide, high-frequency oscillation ventilation, extracorporeal membrane oxygenation, and/or other pulmonary vasodilators could reduce mortality in neonatal persisitent pulmonary hypertension(PPHN). Inhaled nitric oxide is the main method for the treatment of PPHN, which can effectively improve oxygenation and reduce the need for extracorporeal membrane oxygenation(ECMO). The effect of inhaled nitric oxide is different with the gestational age changed.This article aims to summarize the clinical research progress of inhaled nitric oxide in the treatment of PPHN.

Neonatal patent ductus arteriosus accompanied by acute heart failure and pulmonary edema: a case report and literature review / 中国中西医结合急救杂志

Objective To investigate the feasibility and safety of using vasodilators in the treatment of neonates with patent ductus arteriosus (PDA) accompanied by acute heart failure and pulmonary edema. Methods The clinical data of a case of neonatal PDA accompanied by severe cardiac insufficiency and pulmonary edema in Department of Intensive Care Unit (ICU) of Hebei General Hospital, and the neonate's hemodynamic characteristics and the efficacy and adverse reactions of phentolamine, a vasodilator, in the treatment of PDA were retrospectively analyzed. Results In this neonate, on the 8th day after birth and the improvement of pulmonary hyaline membrane disease, the respiratory distress occurred again, which was related to the severe cardiac dysfunction caused by the opening of PDA. Phentolamine was given on the basis of routine treatment to reduce systemic circulatory resistance. Two hours later, the respiratory distress was relieved significantly, that was presumably related to the decline of the left to right shunt volume through the PDA. There were no adverse reactions such as blood pressure reduction and coronary insufficiency. Conclusion Neonatal PDA is easily to be complicated with severe cardiac insufficiency, and vasodilators can reduce systemic circulatory resistance, reduce left to right shunt volume through the ductus arteriosus, and reverse the acute cardiac insufficiency and pulmonary edema, the therapeutic effect of vasodilators is remarkable, safe and reliable in neonatal PDA.

Lesão renal aguda induzida pela sepse e potenciais terapias renoprotetoras / Acute kidney injury induced by sepsis and potential renoprotective therapies

A lesão renal aguda (LRA) é uma complicação comum no paciente grave e está associada à alta mortalidade, tendo a sepse como o mais prevalente fator de risco em pacientes críticos. A LRA na sepse está envolvida com estresse oxidativo e vasoconstrição. Diversas medidas terapêuticas para minimizar os danos renais na sepse já foram investigadas, com destaque para os fármacos antioxodantes, e não se confirmaram como intervenção a ser incorporada na clínica. O objetivo desse estudo foi avaliar a resposta inflamatória sistêmica na sepse, a função renal e os efeitos renoprotetores do vasodilatador cilostazol e dos antioxidantes n-acetilcisteína (NAC) e diosmina hesperidina no modelo de sepse experimental. Foram avaliados parâmetros sistêmicos, o perfil inflamatório renal, intestinal e pulmonar (TGF- e interleucina 6-IL-6), a função renal (FR-clearance de creatinina), a geração urinária de peróxidos (PU) e a análise histopatológica dos rins. Foram utilizados ratos Wistar, machos, divididos em 5 grupos: Sham (controle); Sepse: sepse induzida pela técnica de ligadura e punção do cecon (LPC); Sepse+Cilostazol; Sepse+N-acetilcisteína (NAC) e Sepse+Diosmina. Os resultados mostraram que o grupo Sepse apresentou elevação de TGF- e IL-6 e parâmetros globais como redução da temperatura e hipotensão que caracterizaram o padrão da sepse. Os grupos sepse, tratados ou não, mostraram redução da função renal, com diminuição do fluxo urinário e elevação do parâmetro oxidante analisado, os PUs. Apenas o grupo Sepse+Diosmina demonstrou atenuar a redução da FR desencadeada pela sepse e redução dos PUs na comparação ao grupo Sepse. Todos os grupos sepse apresentaram alterações histológicas renais. O estudo confirmou a LRA por sepse, sendo que apenas o fármaco diosmina hesperidina contribuiu para a melhora da função renal e redução do estresse oxidativo.

Acute renal injury (AKI) is a common complication in critically ill patient and it is associated with high mortality, with sepsis being the most prevalent risk factor for renal failure in critically ill patients. LRA in sepsis is involved with oxidative stress and vasoconstriction. Therapeutic initiatives aimed at minimizing renal damage in sepsis were not confirmed. This study evaluated the systemic inflammatory response in sepsis, renal function and renoprotective effects of the vasodilator cilostazol and the antioxidants n-acetylcysteine (NAC) and diospenes hesperidin. Systemic parameters, the inflammatory renal, in the intestine and in the lungs profile (TGF- and interleukin 6-IL-6), renal function (RF-creatinine clearance), urinary peroxides generation (PU) and histopathological analysis of the kidneys were performed. Male Wistar rats were divided into 5 groups: Sham (control); Sepsis: sepsis induced by the technique of ligation and puncture of the cecon (LPC); Sepsis+cilostazol; Sepsis+N-acetylcysteine (NAC) and Sepsis+diosmin. The results showed that the Sepsis group presented elevation of TGF- and IL-6 and global parameters such as temperature reduction and hypotension characterizing the sepsis pattern. Sepsis groups showed reduced renal function and urinary flow and elevation on UPs. The Sepsis+Diosmina group was the only one to attenuate RF reduction and PU reduction when compared to the Sepsis group. All sepsis groups had renal histological changes. The study confirmed that sepsis induces AKI, being diosmin hesperidin the only agent to contribute to the improvement of renal function and reduction of oxidative stress.

Pharmacological basis for the medicinal use of Michelia champaca in gut, airways and cardiovascular disorders

Objective:To discover the mechanism behind ameliorative effects of Michelia champaca (M. champaca) in gastrointestinal, respiratory and cardiovascular disorders.Methods:Anti- spasmodic potential was evaluated by trying the M. champaca extract (aqueous:ethanolic) on rabbit aorta, trachea and jejunum in vitro. Isotonic and isometric transducers coupled with Power Lab data acquisition system was used to record the responses of isolated tissues.Results:M. champaca extract relaxed the spontaneous and high KConclusion:M. champaca possesses spasmolytic, airways relaxant and vasodilator actions mediated perhaps due to blocking of Ca

Pharmacological basis for the medicinal use of Michelia champaca in gut, airways and cardiovascular disorders

Objective: To discover the mechanism behind ameliorative effects of Michelia champaca (M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Anti- spasmodic potential was evaluated by trying the M. champaca extract (aqueous:ethanolic) on rabbit aorta, trachea and jejunum in vitro. Isotonic and isometric transducers coupled with Power Lab data acquisition system was used to record the responses of isolated tissues. Results: M. champaca extract relaxed the spontaneous and high K

Mecanismos regulatorios del tono vascular pulmonar neonatal: una perspectiva molecular / Regulatory mechanisms of neonatal pulmonary vascular tone: a molecular perspective

La adaptación al medio extrauterino incluye un aumento considerable de la PaO2, que induce especialmente cambios estructurales y vasoactivos en la circulación pulmonar, que llevarán a una circulación previamente pobremente irrigada, a recibir ∼100% del gasto cardíaco del recién nacido, permitiendo el normal intercambio gaseoso. La regulación local de la circulación arterial pulmonar neonatal basal, es mantenida por un delicado equilibrio entre agentes vasoconstrictores y vasodilatadores. Este equilibrio, permite mantener la circulación pulmonar como un territorio de gran flujo sanguíneo y baja resistencia. La acción de los vasoconstrictores permite la formación de las interacciones entre actina y la cadena liviana de la miosina, esta es inducida en la célula muscular lisa principalmente por dos vías: a) dependiente de calcio, que consiste en aumentar el calcio intracelular, facilitando finalmente la unión de actina y miosina, y b) independiente de calcio, la cual a través de consecutivas fosforilaciones logra sensibilizar a las proteínas involucradas promoviendo la unión de actina y miosina. Estas acciones son mediadas por agonistas generados principalmente en el endotelio pulmonar, como endotelina-1 y tromboxano, o por agonistas provenientes de otros tipos celulares como la serotonina. Los agentes vasodilatadores regulan la respuesta vasoconstrictora, principalmente inhibiendo la señalización que induce la vasocontricción independiente de calcio, a través de la activación de proteínas quinasas que inhibirán la función de la ROCK quinasa, uno de los últimos efectores de la vasocontricción antes de la formación de la unión de actina y miosina. Esta revisión describe estos mecanismos de primordial importancia en las primeras horas de nuestra vida como individuos independientes.

The extrauterine-milieu adaptation includes a considerable increase in PaO2, that specifically induces structural and vasoactive changes at pulmonary circulation. Such changes transform a poor irrigated circulation into a circulation that receive ∼100% of neonatal cardiac output, supporting the normal alveolar-capillary gas exchange. Local regulation of basal neonatal pulmonary circulation is maintaining by a delicate equilibrium between vasoconstrictor and vasodilator agents. This equilibrium, allows to maintain the pulmonary circulation as an hemodynamic system with a high blood flow and a low vascular resistance. Vasocontrictors action allows actin and light-chain myosin interaction. Two main pathways induced this effect in smooth muscle cell: a) a calcium dependent pathway, that increases intracellular calcium, facilitating actin - myosin binding, and b) the independent calcium pathway, which achieves through consecutive phosphorylation reactions sensitize the proteins involved, promoting the binding of actin and light-chain myosin. These actions are mediated by agonists produced mainly in the pulmonary endothelium, such as endothelin-1 and thromboxane, or by agonists from other cell types such as serotonin. Vasodilator agents regulate the vasoconstrictor response, mainly by inhibiting signals that induce calcium-independent vasoconstriction, through activation of protein kinases, which in turn will inhibit the function of ROCK kinase, one of the last effectors of vasoconstriction before formation of the actin and light-chain myosin binding. This review will focus on describing these mechanisms of primal importance in the first hours of our lives as independent individuals.

Distorsión morfológica isquémica de la onda T en la centellografía de perfusión miocárdica con estrés vasodilatador / Ischemic T wave distortion associated with vasodilator-stress myocardial perfusion imaging

Los protocolos que utilizan vasodilatadores para inducir isquemia en la centellografía de perfusión miocárdica han demostrado una exactitud diagnóstica elevada e incidencia muy baja de complicaciones graves. Sin embargo, el significado fisiológico y valor diagnóstico de diversas alteraciones electrocardiográficas asociadas al estrés vasodilatador ha sido escasamente evaluado más allá del segmento ST. Describimos cinco pacientes que presentan distorsión morfológica de la onda T en derivaciones electrocardiográficas torácicas asociada a diversos defectos de perfusión, discutiendo los potenciales aportes de estos cambios al diagnóstico y cuantificación de la isquemia miocárdica en los estudios de imagen que utilizan estrés con vasodilatadores.

The protocols using vasodilators to induce ischemia on myocardial perfusion scintigraphy have shown a high diagnostic accuracy and a very low incidence of serious complications. However, the physiological significance and diagnostic value of various electrocardiographic changes associated with vasodilator stress has not been deeply evaluated beyond the ST-segment. Five clinical cases presenting morphological distortion of the T-wave in electrocardiographic chest leads associated with varying degrees of perfusion defects are described, discussing potential contributions of these changes to the diagnosis and quantification of myocardial ischemia in imaging studies using vasodilator stress.

Efecto de la administración prenatal de melatonina en pulmones de neonatos de oveja crónicamente hipóxicos / Effect of prenatal administration of melatonin on lungs of chronic hypoxic sheep neonates

Introducción: Las patologías que podrían motivar el ingreso a una Sala de Reanimación (SR) son múltiples, y asimismo, presentarse en cualquier momento, independientemente del sexo y la edad. A pesar de esta versatilidad, no existen investigaciones que describan la realidad chilena y la literatura extranjera es escasa. En consecuencia, nuestro estudio buscó caracterizar clínico-demográficamente a los pacientes ingresados a SR del Hospital San Juan de Dios de Los Andes, Chile. Materiales y métodos: Estudio de corte transversal. Se trabajó con base de datos anonimizada. El tamaño muestral calculado fue de al menos 1014 sujetos (intervalo de confianza de 95%, precisión de 3%). Se incluyeron los ingresos entre enero de 2013 y junio de 2016, obteniendo una muestra de 1018 pacientes. Variables estudiadas: sexo, edad, diagnóstico general, diagnóstico específico, mes y horario. Se trabajó con Microsoft Excel® utilizando estadística descriptiva. Aprobado por comité éticocientífico. Resultados: 58,1% (n=593) hombres; 42,5% (n=434) mayores de 64 años. Diagnósticos generales más frecuentes: cardiovascular (50,3%) (n=512), neurológico (16,3%) (n=166) y traumático (11,7%) (n=119). Diagnósticos específicos más frecuentes: taquiarritmia (15,9%) (n=162) e infarto miocárdico (12,6%) (n=128). La mayor cantidad de ingresos se registró en enero, febrero y junio (promedio 28 ingresos), y entre las 20 y 00 hrs (22,8%) (n=232). Discusión: Existe un amplio predominio de las enfermedades cardiovasculares.La distribución por mes, sexo y edad parece estar supeditada al comportamiento de dicho grupo; no así la distribución por horarios, ya que las enfermedades cardiovasculares suelen presentarse matinalmente. En general, nuestros resultados coinciden con la literatura extranjera disponible

Introduction: Neonatal pulmonary hypertension (NPHT) caused by chronic hypobaric hypoxia during gestation is associated with oxidative stress and currently lacks of an effective treatment. The aim of this study was to evaluate the effects of melatonin administrated on pregnant sheep on endothelium-dependent vascular reactivity and expression of eNOS, COX-1 and COX-2 on the lungs of lambs gestated and born under chronic hypobaric hypoxia. Material and method: Ten pregnant ewes under chronic hypoxia of highlands (3600 masl) were divided in two groups: 1. Control group (CN), treated with vehicle (5 ml/d ethanol 1, 4%), and 2. Melatonin group (MM), treated with melatonin during gestation (10 mg/d in 5 ml ethanol 1, 4%), during the last third of gestation. Results: Ewes gave birth spontaneously and without assistance, and we obtained lung tissue from 12 days old lambs to determine endothelial vascular reactivity by wire myography. In addition, eNOS, COX-1 and COX-2 RNA and protein expression were measured through RT-PCR and Western Blot, respectively. Discussion: The endothelium dependent vasodilation response was significantly enhanced in MM. Further, MM showed a significant increase in eNOS, COX-1 and COX-2 protein levels, relative to CN group. In conclusion, prenatal melatonin induces endothelium dependent vasodilation mechanisms and positively modulates eNOS-NO and prostanoids pathways, which may favour a treatment for NPHT caused by chronic hypoxia at high-altitude

Development and validation of alternative methods by non-aqueous acid-base titration and derivative ultraviolet spectrophotometry for quantification of sildenafil in raw material and tablets

Sildenafil citrate (SILC) is a potent phosphodiesterase-5 inhibitor used for erectile dysfunction and pulmonary hypertension. This study shows two simple, fast and alternative analytical methods for SILC determination by non-aqueous titration and by derivative ultraviolet spectrophotometry (DUS) in active pharmaceutical ingredient and/or dosage forms. The quantitation method of SILC active pharmaceutical ingredient by non-aqueous acid-base titration was developed using methanol as solvent and 0.1 mol/L of perchloric acid in acetic acid as titrant. The endpoint was potentiometrically detected. The non-aqueous titration method shows satisfactory repeatability and intermediate precision (RSD 0.70-1.09%). The neutralization reaction occurred in the stoichiometric ratio 1:1 in methanol. The determination of SILC active pharmaceutical ingredient or dosage forms by DUS was developed in the linear range from 10 to 40 µg/mL, in 0.01 mol/L HCl, using the first order zero-peak method at λ 256 nm. The DUS method shows selectivity toward tablets excipients, appropriate linearity (R2 0.9996), trueness (recovery range 98.86-99.30%), repeatability and intermediate precision in three concentration levels (RSD 1.17-1.28%; 1.29-1.71%, respectively). Therefore, the methods developed are excellent alternatives to sophisticated instrumental methods and can be easily applied in any pharmaceutical laboratory routine due to simple and fast executions.