Nuevos avances en la terapia de la insuficiencia cardiaca

Las enfermedades del corazón son un tema tratado frecuentemente en las investigaciones médicas, debido a que repercuten ampliamente en el funcionamiento del cuerpo humano. Por lo anterior, se destaca el estudio del tratamiento de las afecciones de este órgano, lo que resulta en una importante tarea para mantener y potenciar los conocimientos sobre los adelantos terapéuticos de las enfermedades relacionadas con el mismo. Se realiza este trabajo con el objetivo de describir los avances en la terapia de la insuficiencia cardiaca. Para ello se realizó una revisión de publicaciones científicas de los últimos dos años. A pesar de que existen diferencias respecto a la terapia propuesta para la insuficiencia cardiaca, las asociaciones americanas y europea de cardiología establecen firmemente la terapia cuádruple (con los inhibidores del receptor de la angiotensina neprilysin, los ß-bloqueadores, los antagonistas de receptor de los mineralocorticoides y los inhibidores del cotransportador-2 de glucosa/sodio) -dirigida a la insuficiencia cardiaca con fracción de eyección reducida-, la recomendación del dinitrato de isosorbide/hidralazina para los pacientes de raza negra, y la utilización de la cardioversión implantable en la prevención de muerte súbita. Se concluye que la armonización de estas guías, en ambos continentes, proporciona un tratamiento único para la insuficiencia cardiaca, aunque necesita un estudio adicional en los pacientes con fracción de eyección del ventrículo izquierdo normal.

Heart diseases are a topic frequently treated in medical researches, due to their wide repercussion on the functioning of the human body; therefore, the study of the treatment of these organ affections is highlighted, being an important task to maintain and enhance knowledge about therapeutic advances in diseases related to it. This work is carried out with the aim of describing the advances in heart failure therapy. A review of the scientific publications of the last two years was performed. Although there are differences regarding the proposed therapy for heart failure, the American and European Associations of cardiology firmly establish the quadruple therapy (with angiotensin receptor inhibitors neprilysin, ß-blockers; mineralocorticoids antagonist receptors and glucose/sodium cotransporters-2 inhibitors-targeted at heart failure with reduced ejection fraction-, the recommendation of isosorbide dinitrate/hydralazine for black patients, and the use of implantable cardioversion in the prevention of the sudden death. It is concluded that the harmonization of these guidelines, in both continents, provides a unique treatment for heart failure, although it needs additional study in patients with normal left ventricular ejection fraction.

Pediatric patients head-up-tilt-test with pharmacological challenge, it is safe? / Mesa inclinada en pacientes pediátricos con reto farmacológico, ¿es seguro?

Abstract Syncope in pediatrics represents an important cause of visits to the emergency units. For this reason, excluding a cardiac or malignant origin is essential at the time of the initial approach to determine what is the next step in management, or if they need to be referred to a pediatric cardiologist and/or electrophysiologist. Vasovagal syncope is the most frequent cause of syncope in pediatrics, in which a detailed clinical history is enough to make the diagnosis. If no diagnosis is concluded by the history, or if it is necessary to define the hemodynamic response of the patients, the head-up-tilt-test is indicated; this will trigger syncope due to an orthostatic stress caused by the angulated table (passive phase). If a negative response remains, it can be followed by a pharmacologic challenge to trigger the hemodynamic response, which is still controversial in pediatrics. The pharmacologic challenge increases the sensitivity with a slight reduction in test specificity. Although there is not a specific drug for the challenge in pediatric patients yet, the most commonly drugs used are nitrates and isoproterenol, the latter related to a great number of adverse effects. Sublingual administration of nitrates in the challenge has been proven to be ideal, effective, and safe in this specific age group. The aim of this article is to make a literature search to demonstrate the effectiveness and safety of the pharmacologic challenge during the head-up-tilt-test in pediatrics, emphasizing a study conducted at the National Institute of Cardiology with isosorbide dinitrate.

Resumen El síncope en edades pediátricas representa una causa importante en las visitas a unidades de urgencias, por lo que excluir un origen cardíaco o maligno es fundamental al momento del abordaje inicial para determinar la conducta a seguir o la necesidad de derivar al cardiólogo pediatra o electrofisiólogo. El síncope vasovagal (SVV) es la causa más frecuente de síncope en pediatría, para cuyo diagnóstico basta una historia clínica detallada. Cuando ésta no es suficiente para determinar el diagnóstico de síncope reflejo o es necesario definir el tipo de respuesta que lo origina, está indicada una prueba de mesa inclinada que produce un estrés ortostático por la angulación y ello desencadena un síncope (fase pasiva). En pruebas no concluyentes está indicado un reto farmacológico para precipitar la respuesta hemodinámica, pero aún es un tema de controversia en edades pediátricas. El reto farmacológico incrementa la sensibilidad de la prueba, con una ligera reducción de la especificidad. Si bien no existe todavía un medicamento específico para la población pediátrica, los más empleados son los nitratos y el isoproterenol, este último relacionado con un mayor número de efectos adversos. La administración sublingual de los nitratos utilizados ha demostrado ser ideal, efectiva y segura en los pacientes pediátricos. El objetivo del artículo es realizar una revisión de las publicaciones médicas que demuestran la efectividad y seguridad del reto farmacológico durante la prueba de mesa inclinada en pacientes pediátricos, con énfasis en un estudio conducido en el Instituto Nacional de Cardiología con dinitrato de isosorbida (DNIS).

The effect of isosorbide dinitrate on cardiac function after cardiopulmonary resuscitation in a porcine model / 中华急诊医学杂志

Objective To assess the effect of isosorbide dinitrate on the improvement of cardiac function after cardiopulmonary resuscitation (CPR) by regulating myocardial cells apoptosis..Methods Total of 30 domestic pigs were divided into three groups randomly (random mumber) after anesthetization:the sham group (n=6),the control group (n=12),and the isosorbide dinitrate group (n=12).Cardiac arrest of ventricular fibrillation was induced by programed electrical stimulation in the control and isosorbide dinitrate groups.Isosorbide dinitrate was infused at the rate of 2 μg/(kg·min) in the isosorbide dinitrate group.Coronary perfusion pressure (CPP) and cardiac output (CO) were recorded at baseline,2,6,12 and 24 h after restoration of spontaneous circulation (ROSC).Myocardial enzyme and heart fatty acid binding protein (H-FABP) was tested at the same time points.At 24 h after ROSC,the animals were sacrificed to obtain the myocardium for pathological section and Western blot.The expression of Bcl-2,Bax and activated Caspase-3 were tested and apoptosis was tested by TUNEL and apoptosis index was calculated.Results Right atrial pressure (RAP) increased after ROSC and decreased in the isosorbide dinitrate group compared with the control group (P＜0.05).CPP at 12,24 h after ROSC and CO at 24 h after ROSC in the isosorbide dinitrate group increased significantly compared with the control group (both P＜0.05).HE staining revealed that the injury of myocardial cells was ameliorated in the isosorbide dinitrate group.Apoptosis index of the isosorbide dinitrate group significantly decreased than the control group [(37.8±15.5)％ vs (13.1±0.5)％,P＜0.05].The expression of Bax and activated Caspase-3 decreased while Bcl-2 and Bcl-2/Bax increased after ROSC in the isosorbide dinitrate group compared with the control group (all P＜0.05).Conclusions Isosorbide dinitrate could improve the isehemia/reperfusion injury and cardiac function after ROSC by inhibiting apoptosis regulated with Caspase-3 pathway.

Clinical efficacy and safety of Danshen Chuanxiongqin injection combined with Isosorbide dinitrate in the treatment of myocardial ischemia / 中国生化药物杂志

Objective To observe the clinical efficacy and safety of Danshen Chuanxiongqin injection combined with Isosorbide dinitrate on the treatment of myocardial ischemia.Methods 78 patients with myocardial ischemia from January 2015 to July 2016 were divided into the observation group and the control group, with 39 cases in each group.The control group received Isosorbide dinitrate therapy, the observation group received Danshen Chuanxiongqin injection joint Isosorbide dinitrate therapy.To analysis the clinical efficacy,electrocardiogram, TG,TC,the whole blood high and low-shear viscosities and adverse reactions between two groups.Results After treatment, total effective rate of the observation group was 89.74%, higher than the control group with 66.67%( P<0.05 ) .After treatment, ST segment depression occurred frequency and ST segment depression duration time of two groups were lower than before treatment(P<0.05),ST segment depression occurred frequency and ST segment depression duration time of observation group were lower than the control group (P<0.05).After treatment, TG and TC level of two groups were lower than before treatment(P<0.05),TG and TC level of the observation group were lower than the control group (P<0.05).After treatment,the whole blood high and low-shear viscosities of two groups were lower than before treatment(P<0.05),the whole blood high and low-shear viscosities of the observation group were lower than the control group ( P <0.05 ) .During treatment, there was no significant difference in adverse reaction rate between the two groups.Conclusion Danshen Chuanxiongqin injection combing with Isosorbide dinitrate has a better efficacy on the treatment of myocardial ischemia than only Isosorbide dinitrate ,and it is a safe treatment therapy.

Formulation and evaluation of transdermal drug-delivery system of isosorbide dinitrate / Formulação e avaliação de sistema transdérmico droga-entrega de dinitrato de isossorbida

The purpose of this study was to develop a reservoir-type transdermal delivery system for isosorbide dinitrate (ISDN). The developed patch consisted of five layers from bottom to top, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing. The effects of chemical penetration enhancers, reservoir materials and rate-controlling membranes on the release behaviour of ISDN from the transdermal patch were studied, and the in vitro release of ISDN from the developed patch was studied and compared with the commercially available ISDN patch. The results showed that there was no significant difference in permeation rates between the developed reservoir-type patch and the commercially available ISDN patch (p> 0.05). Moreover, the cumulative release ratio of the commercially available ISDN patch in 48 h was up to 89.8%, whereas the developed patch was only 34.9%, which meant the sustained release time of the developed patch was much longer than the commercially available ISDN patch, and would promote the satisfaction of the patient...

O objetivo do presente estudo foi desenvolver um sistema de liberação transdérmico do tipo reservatório para o dinitrato de isossorbida (ISDN, abrevitura em Inglês). A formulação transdérmica desenvolvida constou de cinco camadas de baixo para cima, ou seja, um revestimento temporário, uma camada adesiva, uma membrana controladora da taxa de liberação, um reservatório e um reforço. Estudaram-se os efeitos dos potenciadores de penetração química, materiais do reservatório e membranas de controle da taxa de liberação no comportamento da formulação transdérmica de dinitrato de isossorbida. A liberação in vitro da formulação transdérmica de dinitrato de isossorbida desenvolvida foi estudada em comparação com a formulação de dinitrato de isossorbida disponível comercialmente. Os resultados mostraram que não existem diferenças significativa nas taxas de permeação entre o tipo de reservatório desenvolvido e o de dinitrato de isossorbida desenvolvido comercialmente (p>0,05). Ademais, a taxa de liberação cumulativa da formulação de dinitrato de isossorbida disponível comercialmente em 48 horas foi de até 89,8% e a da formulação desenvolvida, de apenas de 34,9%, o que provou que a liberação sustentada da formulação desenvolvida foi muito maior do que a de dinitrato de isossorbida desenvolvida comercialmente, o que promoveria a satisfação do paciente...

A Double-Blind Randomized Trial Comparing the Effectiveness and Safety of Nifedipine and Isosorbide Dinitrate in Chronic Anal Fissure

Background: Chronic anal fissure is a common disease that is accompanied with pain and bleeding during defecation. Various surgical and non-surgical methods have been offered for the treatment of this condition. Objective: The aim of this randomised clinical study was to compare the effectiveness and safety of nifedipine and isosorbide dinitrate (ISDN) in the treatment of chronic anal fissure. Methods: This double-blind clinical trial study was performed on patients aged 20 to 60 years old in 2012 to 2013. The samples with a primary diagnosis of chronic anal fissure were enrolled from the patients admitted to public treatment at the educational Imam Ali Clinic, Shahrekord, Iran by researchers and general surgery specialists. The patients were randomised into two groups: nifedipine 0.3% (n = 35) or ISDN 0.2% (n = 35) applied three times a day for three weeks. The patients were examined on the 7th, 14th, and 21st days of treatment, and the symptoms including bleeding, pain, and healing status, as well as the side effects of the drugs, were assessed. Pain was evaluated using a visual analogue scale (VAS). Results: After 21 days of follow-up, complete healing was achieved in 77.1% (n = 27) of patients in the nifedipine group and 51.4% (n = 18) in the ISDN group (P = 0.05). The mean VAS of the pain on day 21 was 0.91 (SD 0.01) in the ISDN group and 0.45±0.78 in the nifedipine group, with a statistically significant difference (P = 0.038). The bleeding was similar in the two groups (P = 0.498). Conclusion: In view of the findings on healing status and pain in the patients, nifedipine may be significantly more effective in the treatment of chronic anal fissure than ISDN.

Clinical efifcacy of Yixinshu capsule combined with isosorbide dinitrate tablets in the treatment of stenocardia / 中国生化药物杂志

Objective To analyze and explore the clinical efifcacy of Yixinshu capsule combined with isosorbide dinitrate tablets in the treatment of stenocardia. Method 72 patients with stenocardia in cardiovasology of Zizhong county people’s hospital of Sichuan province were randomly divided two groups,36 cases in each group. Control group was treated with isosorbide dinitrate tablets, experimental group was given both Yixinshu capsule and isosorbide dinitrate tablets. Clinical efifcacy, adverse reactions and patients’satisfaction in two groups were analyzed comparitively. Results After treatment, the total effective rate and satisfaction degree in experimental group were signiifcantly higher than control group.Incidence of adverse reactions of experimental groupwas signiifcantly lower than control group(P<0.05). Conclusion Clinical efifcacy of Yixinshu capsule combined with isosorbide dinitrate tablets in the treatment of stenocardia is signiifcantly higher than single isosorbide dinitrate tablets, with higher satisfaction degree and lower incidence of adverse reactions, which can be widely applied in clinic.

Diagnostic value of head-up tilt test with sublingual isosorbide dinitrate in patients with vasovagal syncope / 心血管康复医学杂志

Objective: To explore the diagnostic value of head-up tilt test with sublingual isosorbide dinitrate （HUTSI）in patients with vasovagal syncope (VVS). Methods: A total of fifty-two consecutive patients with clinically vasovagal syncope (VVS group) and thirty-eight control subjects without prior experience of syncope (normal control group) were evaluated by baseline head-up tilt table test (BHUT) , then the BHUT negative subjects underwent HUTSI test. . Results: (1) Positive BHUT test rate of VVS group and normal control group were 25% (13/52) and 0 respectively; from supine to HUT positive, there were significant decrease in heart rate [(73.1±8.5) times/min vs. (56.2±11.2) times/min] and mean arterial pressure [MAP, (81.2± 10.8) mmHg vs. (50.2±10.4) mmHg，P<0.05 both] in BHUT positive subjects. There were 21 HUTSI positive cases（53.9%）among the other 39 VVS patients, and two cases（5.3%）among the 38 subjects of normal control group. From supine to HUTSI positive, there were significant decrease in heart rate [(65.2±7.5) times/min vs. (52.9±10.5) times/min] and MAP [(78.3±10.7) mmHg vs. (48.8±11.2) mmHg, P<0.05 both] in HUTSI positive subjects. Duration from tilt started to positive reaction occurred in HUTSI positive group was significantly shorter than that of BHUT positive group [(10.8±9.3) min vs. (21.1±11.5) min，P<0.05]. All subjects can tolerate the test and only two cases in VVS group and one case in normal control group occurred headache and face red. Conclusion: Head-up tilt test with sublingual isosorbide dinitrate is a practical and easy-to- perform method with high sensitivity, specificity and few side effects for diagnosis of vasovagal syncope.

Efeito do dinitrato de isossorbida sobre a hiperalgesia corneana induzida por lipopolissacarídeo / Isosorbide dinitrate effect on corneal hyperalgesia induced by lipopolysaccharide

OBJETIVO: Avaliar o efeito do dinitrato de isossorbida (DNI) sobre a hiperalgesia corneana e a infiltração de neutrófilos em um modelo experimental de ceratite superficial induzida pelo lipopolissacarídeo (LPS). MÉTODOS: A hiperalgesia foi estudada através da indução de uma ceratite inflamatória em ratos (n = 60), pela exposição da córnea ao LPS (LPS +). Após a exposição, os olhos foram tratados durante quatro dias, com as soluções tópicas: DNI (200 mg, 65 mg e 20 mg), prednisolona 1 por cento (PRED) ou Veículo. Olhos controles foram expostos apenas à solução salina (LPS -). Para avaliar a dor ocular, contouse o número de piscadas em 40 segundos, após instilação de uma gota de capsaicina 0,01 mM. A análise histopatológica foi realizada para avaliação da infiltração neutrofílica. RESULTADOS: Foram observadas áreas esbranquiçadas no estroma corneano dos olhos com a ceratite induzida pelo LPS, entre os dias 3 e 15 dias. Esses olhos (LPS +) apresentaram um número significativamente maior de piscadas que os LPS - (P = 0,019) à estimulação química. O tratamento tópico com o DNI reduziu o número de piscadas observadas (P = 0,010). Da mesma forma, olhos expostos ao LPS e tratados com DNI demonstraram redução significativa na infiltração neutrofílica (P = 0,0031). CONCLUSÃO: Baixas doses de DNI reduziram a hiperalgesia corneana e a infiltração neutrofílica nesse modelo de ceratite. Dessa forma, doadores de óxido nítrico, como o DNI, poderão ser úteis no futuro ao tratamento clínico de diversas condições dolorosas da superfície ocular.

PURPOSE: To analyze effects of isosorbide dinitrate (DNI) on corneal hyperalgesia and neutrophil infiltration in an experimental model of superficial keratitis induced by lipopolysaccharide (LPS). METHODS: Hyperalgesia was studied through the induction of inflammatory keratitis in rats (n=60), by corneal exposure to LPS. Following exposure, the inflamed eye was treated for four days, with one of the following solutions: topical DNI (200 λg, 65 λg and 20 λg), prednisolone 1 percent (PRED), and vehicle. Saline-exposed eyes (LPS -) underwent the same protocol. To evaluate ocular pain, the number of blinks in 40 seconds was counted, after one drop of 0.01 λM capsaicin. Histopathological analysis was performed with evaluation of neutrophil infiltration. RESULTS: White clouding areas were observed in the corneal stroma of eyes with LPS-induced keratitis, between day 3 and day 15. Eyes exposed to LPS had a significantly higher number of blinks than LPS - (P=0.019). Topical treatment of LPS-induced keratitis eyes with DNI reduced capsaicin-induced blinks (P=0.010). Similarly, eyes exposed to LPS and treated with DNI also displayed reduced neutrophil infiltration (P=0.0031). CONCLUSION: Low doses of topical NO donors, like DNI, reduce corneal hyperalgesia and neutrophil infiltration in this keratitis model. NO donors may be useful in the clinical treatment of painful conditions associated with surgical procedures of the ocular surface.

Study of efficacy and safety of a new local cream ("healer") in the treatment of chronic anal fissure: a prospective, randomized, single-blind, comparative study / Estudo da eficácia e segurança de novo creme cicatrizante para o tratamento da fissura anal crônica: estudo prospectivo, randomizado, simples-cego e comparativo

OBJECTIVES: To determine the efficacy and safety of "healer" cream as monotherapy in the treatment of acute and chronic anal fissure. STUDY DESIGN: A prospective, randomized, single blinded, comparative trial. METHODS: Sixty patients suffering from anal fissure were included in the study. Patients were randomly divided into three groups: group A: treated with "healer" local cream application 3 times daily; group B: treated with nitroglycerine 0.25 percent local cream 3 times daily; group C: treated with a lidocaine 2 percent cream applied locally 3 times daily. All the followings were followed up and compared between groups. (1) Visual pain analogue score after defecation; (2) severity of straining and discomfort during defecation; (3) frequency of ulcer healed at 30 days; (4) any side effects or complications. RESULTS: The pain scoring after defecation was significantly reduced in the three treatment groups. The group treated with "healer" isosorbide-di-nitrate showed the greatest reduction of the visual pain analogue score median from 9 before treatment to 3 & 1 after 10 and 20 days respectively, while the median visual pain analogue score in group B treated with nitroglycerine cream was 9 reduced to 4 & 2 after 10 and 20 days respectively, and the median visual pain analogue score in lidocaine group only dropped from 9 to 6 and 4, respectively. The reduction of both pain scoring and defecation scoring with "healer" was statistically significantly greater than the other two treatments by Kruskal-Wallis test, P<0.001. The number of patients experiencing complete relief and passing stools easily after 10 days was significantly higher in "healer" group, by Pearson Chi square = 22.94, P<0.001. After 30 days, the fissures were healed in 18 (90 percent) of 20 patients in the "healer" group and in 12 (60 percent) of 20 in the nitroglycerin group, while only 6 (30 percent) of patients treated with lidocaine cream had their fissures healed by ...

OBJETIVOS: Determinar a eficácia e segurança de "creme cicatrizante" (dinitrato de isosorbida 1 por cento; lidocaína 2 por cento; rutosídios 5 por cento em base de creme anti-séptico) como monoterapia no tratamento da fissura anal aguda ou crônica. METODOLOGIA: Estudo prospectivo, randomizado, simples-cego, comparativo. Foram incluídos 60 pacientes com fissura anal. Foram divididos randomicamente em três grupos: grupo A: tratados com "creme cicatrizante", grupo B: tratados com creme de nitroglicerina 0,25 por cento e grupo C: tratados com creme de lidocaína 2 por cento aplicado. Em todos foi feita aplicação local 3 vezes ao dia. Os seguintes parâmetros foram aferidos: 1) escore analógico visual de dor após defecação, 2) severidade de esforço e desconforto para evacuar, 3) frequência da cicatrização após 30 dias, 4) presença de efeitos colaterais ou complicações. RESULTADOS: O escore de dor após a defecação foi reduzido significativamente nos três grupos. O grupo tratado com creme cicatrizante mostrou grande redução do escore médio de 9 para 3 e 1 após 10 e 20 dias de tratamento, respectivamente, enquanto que a média do grupo B foi reduzida de 9 para 4 e 2 e do grupo C de 9 para 6 e 4 após 10 e 20 dias de tratamento, respectivamente. A redução tanto da dor como do desconforto evacuatório com o uso de "creme cicatrizante" foi significativo em comparação com os outros cremes pelo teste de Kruskal-Wallis, P<0,001. O número de pacientes que referiram alívio completo e passagem fácil da fezes após 10 dias de tratamento foi maior e significativo no grupo A pelo teste Pearson, P<0,001. Após 30 dias, as fissuras estavam cicatrizadas em 18 (90 por cento) pacientes do grupo A, em 12 (60 por cento) do grupo B e em apenas 6 (30 por cento) do grupo C. Qui ao quadrado = 15 (P = 0,001). CONCLUSÃO: O "creme cicatrizante" é um tratamento que promete ser promissor e seguro na fissura anal aguda ou crônica. A característica farmacocinética do creme leva ...

The Effect of Isosorbide Dinitrate Intravenous Injection on the Hemodynamics and Arterial Stiffness of Patients with Isolated Systolic Hypertension

BACKGROUND AND OBJECTIVES: In clinical practice, isolated systolic hypertension (ISH) is common for elderly patients and it is correlated with cardiovascular mortality. However, it is difficult to control the systolic blood pressure (BP) with using the currently available antihypertensive drugs without influencing the diastolic BP. The purpose of this study is to evaluate the effect of isosorbide dinitrate on the central BP and arterial stiffness by performing invasive testing. SUBJECTS AND METHODS: Thirty subjects who had ISH and who underwent coronary angiography were enrolled in this study. The invasively measured central blood pressure, pulse pressure and pulse wave velocity were obtained after isosorbide dinitrate was injected intravenously and these values were analyzed in relation to age, gender, the body mass index, diabetes mellitus, dyslipidemia, smoking and the current dosing with antihypertensive drugs. RESULTS: One minute after intravenous injection of isosorbide dinitrate, the central systolic BP was significantly decreased compare to the baseline value (142.23+/-12.32 mmHg vs 164.97+/-14.43 mmHg, respectively, p<0.001), and this change was sustained for 5 minutes (141.05+/-14.84 mmHg vs 164.97+/-14.43 mmHg, respectively, p<0.001). The mean values, during the 5 minute period, of the pulse pressure (65.99+/-13.63 mmHg vs 87.30+/-13.71 mmHg, respectively, p<0.001) and the pulse wave velocity (11.22+/-3.20 m/sec vs 12.91+/-4.11 m/sec, respectively, p<0.001) also revealed significant changes. Yet there was no significant decrease of the diastolic BP. Analysis of subgroups that were classified by gender, age, BMI, diabetes mellitus, dyslipidemia, smoking, the degree of the systolic BP and PWV, and taking antihypertensive drugs showed a similar pattern. CONCLUSION: Isosorbide dinitrate was very effective for selective control of the systolic BP in ISH patients. It is also expected to prevent cardiovascular complications by improving arterial stiffness.

The cytoprotective effect of a nitric oxide donor drug on gastric mucous membrane of rats treated with ketoprofen, a non-steroidal anti-inflammatory drug / Efeito citoprotetor de uma droga doadora de óxido nítrico na membrana da mucosa gástrica de ratos tratados com o antiinflamatório não-esteróide - o cetoprofeno

BACKGROUND: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent. AIM: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment. METHODS: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration. RESULTS: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared...

RACIONAL: Drogas antiinflamatórias não-esteróides são consideradas, atualmente, importante grupo de medicamentos, com ampla variedade de uso terapêutico, em diferentes áreas da medicina moderna. Apesar de seus efeitos benéficos para o paciente, apresentam grande incidência de efeitos colaterais, principalmente no trato gastrointestinal. Os mecanismos fisiopatológicos de lesões induzidas por essas drogas e os mecanismos de defesa da mucosa gástrica tornaram-se uma importante linha de pesquisa médica, especialmente procurando avaliar o papel de óxido nítrico como agente citoprotetor. OBJETIVO: Estudar uma droga doadora de ácido nítrico - o dinitrato de isossorbida - e sua ação citoprotetora da mucosa gástrica de ratos submetidos ao tratamento com uma droga antiinflamatória - o cetoprofeno. MÉTODOS: Ratos machos adultos previamente submetidos a jejum de 24 horas, foram divididos em três grupos: a) grupo I (controle): animais, que receberam apenas solução salina isotônica via intragástrica, por gavagem e via endovenosa; b) grupo II (cetoprofeno-controle): animais que receberam solução salina via intragástrica por gavagem e cetoprofeno via endovenosa, e c) grupo III (nitrato/cetoprofeno): animais que receberam solução de 2 mM de dinitrato de isossorbida a via intragástrica por gavagem e cetoprofeno via endovenosa. Esses grupos foram, posteriormente, submetidos a exames macroscópico, microscópico e bioquímico, avaliando-se os seguintes parâmetros: a) determinação do índice de lesão gástrica; b) determinação da espessura da camada do muco secretor; c) determinação da concentração de ácido nítrico x tecidual, e d) determinação da concentração do malondialdeído tecidual. RESULTADOS: Encontrou-se menor índice de lesão gástrica nos animais do grupo III (nitrato), assim como maior espessura da camada do muco secretor nos animais deste grupo, do que nos animais do grupo II (cetoprofeno). A variação da concentração do ácido nítrico x tecidual foi semelhante nos três grupos. A taxa...

Effect of Glyceryl Trinatrate and Isosorbide Dinitrate Against Replication of Coxsackievirus B3 in vivo / 医学研究杂志

Objective To provide an experimental evidence for the clinical applications of glyceryl trinatrate(GTN)and isosorbide dinitrate(ISDN)against Coxsackievirus B(CVB)-related myocarditis.Methods Coxsackievirus B3 was propagated in HeLa cells.Virus yields were determinded by 50% tissue culture infective dosage(TCID50).BALB/c mice were attacked with 5000 TCID50 of CVB3,meanwhile,the mice were administrated with GTN and ISDN.All mice were killed at the 14th day.The myocardial tissues were harvested for histologic evaluation.Results The infection plaques in the myocardial tissues obtained from CVB3-infected BALB/c mice treated with GTN were siginificantly reduced(0.89?0.18 in GTN group and 1.25?0.22 in ISDN group)compared with that of the untreated CVB3-infected mice(P

Study on preparation of isosorbide dinitrate in conditions of Vietnam

Using sorbitol - a cheap and easy-to-find material in Vietnam, the authors built a relative optimal and complete protocol to synthesize isosorbide and isosorbide dinitrate (productivity of 64%). Test purity isosorbide dinitrate and solution of 25% isosorbide dinitrate. With purity isosorbite dinitrate: qualitative analysis by IR and test by HPLC method were conducted; isosorbide dinitrate solution was test according to USP 24 and checked by this standard. All products meet USP 24 standard

Comparative study of Xuesaitong injection and isosorbide mononitrate injection on patients with stable angina / 中国基层医药

Objective To evaluate the effect and safety of Xuesaitong injection (XST) in stable angina. Methods The effects on XST and(or) isosorbide mononitrate injection(IM) were compared with that of placebo in 147 cases with stable angina.40 cases were performed XST 10ml per day,65 cases IM 20mg per day and 42 cases both XST and IM. Results XST injection was effective on relieving symptoms,improving curative effect of electrocardiogram, decreasing levels of serum TCLDL and adhesive rate of platelet, union of XST and IM might obtain better curative efect. Conclusion XST is an effective and safe drug in stable angina.

A Ratio of Arterial Oxygen Tension to Inspired Oxygen Fraction (PaO2/FiO2 ratio) after Cardiopulmonary Bypass in Coronary Artery Bypass Graft Surgery: Amrinone-Dopamine versus Isosorbide Dinitrate-Dopamine / 대한마취과학회지

BACKGROUND: Cardiopulmonary bypass (CPB) may produce lung injury with decreased PaO2/FiO2 ratio in patients undergoing CABG surgery. We examined PaO2/FiO2 ratio and incidence of PaO2/FiO2 < 300 or 150 to determine the differences in oxygenation with the use of amrinone-dopamine (DP) or isosorbide dinitrate (IDN)-DP in patients undergoing CABG. METHODS: Twenty patients undergoing elective CABG were divided into two groups according to drug used on separation from CPB: IDN-DP (Group 1, n = 10) or amrinone-DP (Group 2, n = 10). Anesthesia was induced and maintained with propofol, fentanyl and vecuronium. IDN infusion (1.0microgram/kg/min) was started preoperatively in both groups. Mild hypothermic CPB was applied with a roller pump and nonpulsatile flow maintained a mean arterial pressure of 60-80 mmHg. In Group 2, amrinone was administered (0.75 mg/kg + 10microgram/kg/min) instead of IDN at the time of CPB separation. DP infusion (3microgram/kg/min) was started at a rectal temperature more than 35.5oC and adjusted to maintain acceptable hemodynamics. IDN-DP or amrinone-DP infusion, monitoring and sedation with propofol were continued in the intensive care unit (ICU). PaO2/FiO2 ratio under controlled ventilation with air/O2 mixture (FiO2 0.6) was checked immediately before CPB (pre-CPB), 30 mins (post-CPB30), 60 mins after CPB (post-CPB60) and 30 mins after admission to ICU (ICU30). RESULTS: There was no significant difference between the groups in the terms of the duration of arotic cross clamp, PaO2/FiO2 at pre-CPB, PaO2/FiO2 at post-CPB60, PaO2/FiO2 at ICU30 or in the incidence of PaO2/FiO2 < 150, PaO2/FiO2 < 300 at ICU30. But there was a significant difference in PaO2/FiO2 post CPB30 (263.3 +/- 105.5 in Group 1 vs. 381.7 +/- 69.5 in Group 2, P<0.05). CONCLUSIONS: Amrinone-DP provides more favorable oxygenation immediately after CPB in CABG surgery than IDN-DP.

Clinical evaluation of prostaglandin E_1 liposome in treatment of patients with unstable angina pectoris / 中国临床药理学与治疗学

0.05 )between control group and treatment group. The relapse rates of two weeks were different remarkably (P

Dinitrato de isosorbide sublingual en la urgencia hipertensiva

Se investigó el uso del dinitrato de isosorbide sublingual en la urgencia hipertensiva. Se estableció además una correlación con la nifedipina, de eficacia probada para este fin. Se estudiaron 80 pacientes con este diagnóstico, distribuidos aleatoriamente en 2 grupos, que recibieron 10 mg de nifedipina o dinitrato de isosorbide, si a los 45 min de la primera dosis no se había alcanzado el control se administró una segunda dosis. Se obtuvo la primera dosis de dinitrato de isosorbide, un mayor número de pacientes controlados (n = 29) a diferencia de la nifedipina (n = 19). Ambos fármacos lograron el control de 36 pacientes con la segunda dosis. La nifedipina causó cefalea ligera. En conclusión, el dinitrato de isosorbide resultó ser un medicamento eficaz, de fácil administración y con escasos efectos secundarios en el tratamiento de la urgencia hipertensiva y puede constituir una alternativa más en los servicios de urgencia.

The use of sublingual isosorbide dinitrate in the hypertensive urgency was investigated. It was also established a correlation with nifedipine, whose efficacy has been proved to this end. 80 patients with this diagnosis were studied and divided at random into 2 groups, who received 10 mg of nifedipine or isosorbide dinitrate and a second dosage if their pressure was not controlled 45 minutes after the first dosage. With the first dosage of isosorbide dinitrate a higher number of patients were controlled (n = 29) compared with nifedipine (n = 19). 36 patients were controlled with the second dosage of both drugs. Nifedipine caused mild cephalalgia. To conclude, isosorbide dinitrate proved to be an efficient drug, easy to administer and with a few side effects in the treatment of hypertensive urgency. It may be another alternative for urgency services.

Accuracy of low dose dobutamine,isosorbide dinitrate alone and in combination stress echocardiography for identifying viable myocardium in patients with old myocardial infarction and severe left ventricular dysfunction:compared with ~(99m)Tc-MIBI/~(18)FDG / 中华超声影像学杂志

(0.05)). The sensitivity and the agreement rate were best at dose of Dob 10 ?g?kg~(-1)?min~(-1) with (86.5)% and (86.5)% (Kappa(0.71)), respectively. When Isoket combined with Dob 3,5 ?g?kg~(-1)?min~(-1), the sensitivities and the agreement rates were both significantly improved than either one used (both P

Vasodilator Properties of Nitroglycerin, Isosorbide Dinitrate and Chlorpromazine during Cardiopulmazine during Cardiopulmonaty Bypass / 대한마취과학회지

In a placebo-controlled trial, we have studied the vasodilator properties of bolus dose of nitroglycerin, isosorbide dinitrate and chlorpromazine in 38 patients during cardiopulmonary bypass with a constant pump flow. Mean arterial pressure and blood volume of the venous reservoir were recorded for 10 min after drug administration to detect changes in arteriolar resistance and venous capacitance, respectively. Nitroglycerin, 2.5 ug/kg, decreased arterial pressure, but the effect lasted for 3 minutes. Chlorpromazine, 0.1 mg/kg, decreased arterial pressure for 9 minutes. Isosorbide dinitrate, 20 ug/kg, had no significant change on arterial pressure. The venous capacitance-increasing effects of nitroglycerin and chlorpromazine were significant for 4 minutes after the bolus. Thereafter the effect of nitroglycerin began to decline, while that of chlorpromazine significantly continued. Isosorbide dinitrate had no significant change on venous reservoir level. The SVR reduction effects of nitroglycerin was significant for 3 minutes, chlorpromazine decreased SVR for over 10 minutes. In conclusion chlorpromazine effect on arterial pressure and venous capacitance was more potent and longer than nitroglycerin and isosorbide dinitrate. Nitroglycerin and chlorpromazine effect on preload and afterload were significant after bolus dose.