Interleukin-37 has A Promising Cardioprotective Effect on Isoproterenol-Induced Myocardial Infarction / La Interleucina-37 tiene un Efecto Cardioprotector Prometedor sobre el Infarto de Miocardio Inducido por Isoproterenol

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.

La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.

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).

histological and immunohistochemical study on the possible protective effect of omega-3 polyunsaturated fatty acids on isoprenaline induced myocardial fibrosis in rats

Preclinical and clinical studies have demonstrated that omega-3-polyunsaturated fatty acids [omega-3-PUFAs] play a significant role in the prevention of cardiovascular diseases. This study aimed to investigate the possible protective effect of omega-3-PUFAs on isoprenaline [ISP]-induced myocardial fibrosis. Thirty-two adult male albino rats were divided into five groups. Group I represented the control group [eight rats]. In group II, six rats were given omega-3-PUFAs [40 mg/kg/day] orally for 8 weeks. In group III, six rats were injected subcutaneously with ISP [5 mg/kg/day] for 4 consecutive days and sacrificed 2 days later. In group IV, six rats were injected with ISP [5 mg/kg/day] for 4 consecutive days and sacrificed after 2 weeks. In group V, six rats were given omega-3-PUFAs [40 mg/kg/day] for 8 weeks, following which they were injected with ISP [5 mg/kg/day] for 4 consecutive days, and sacrificed 2 days later. Serum creatine phosphokinase-MB [CPK-MB] was measured. Myocardial sections were subjected to H and E, Masson's trichrome stain, and alpha-smooth muscle actin [alpha-SMA] immunohistochemical stain. Group II showed nonsignificant difference in the mean CPK-MB level compared with the control. Myocardial sections revealed a histological architecture similar to that of the control. The mean area% of collagen and alpha-SMA immunoreactivity was nonsignificant when compared with the control. Group III showed significant increase in mean CPK-MB compared with the control. Myocardial sections showed disorganization, inflammation, exudation, and fibrosis with significant increase in the mean area% of collagen and alpha-SMA immunoreactivity compared with the control. Group IV showed significant increase in mean CPK-MB, area% of collagen, and alpha-SMA immunoreactivity compared with the control, with progression in the myocardial histological alterations. Group V showed significant decrease in the mean CPK-MB with decrease in histological changes, and there was significant decrease in the mean area% of collagen and alpha-SMA immunoreactivity compared with the ISP groups. omega-3-PUFAs exert cardioprotective effects against ISP-induced myocardial fibrosis

Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos / Experimental model of myocardial infarction induced by isoproterenol in rats

OBJETIVO: Avaliar e validar, em nosso meio, o modelo de infarto do miocárdio induzido por isoproterenol em ratos por meio de análises de parâmetros hematológicos, bioquímicos, de marcadores do estresse oxidativo e histopatológicos. MÉTODOS: Trinta ratos jovens, machos, da linhagem Wistar (145 a 230 g), foram alocados aleatoriamente em dois grupos: grupo Simulado, submetido à falsa indução de infarto do miocárdio, e grupo Infarto, submetido à indução do infarto do miocárdio com isoproterenol. As aplicações, para indução do infarto, foram realizadas durante dois dias consecutivos, com intervalo de 24 horas entre elas. Após 24 horas da última aplicação, os ratos de ambos os grupos foram anestesiados e sacrificados para realização de coleta de sangue para hemograma e análise bioquímica (TGO, TGP, troponina I, ureia e creatinina) e coleta de fragmento do miocárdio para avaliação de marcadores do estresse oxidativo (atividade da catalase e concentração de glutationa) e exame histopatológico. RESULTADOS: Não houve mortalidade no grupo Simulado, enquanto a mortalidade no grupo Infarto foi de 25%. A indução do infarto do miocárdio com isoproterenol causou elevação das contagens de leucócitos e neutrófilos, dos níveis de TGO, troponina I e ureia, reduziu a atividade da catalase e os níveis teciduais de glutationa e causou alterações histopatológicas. Não acarretou alterações nas concentrações de hemoglobina, TGP e creatinina. CONCLUSÕES: O modelo de infarto do miocárdio induzido por isoproterenol em ratos foi adequadamente reproduzido em nosso laboratório, acarretando alterações em parâmetros hematológicos, bioquímicos, de marcadores de estresse oxidativo e histopatológicos.

OBJECTIVE: To evaluate and validate, in our laboratory, the essay of myocardial infarction induced by isoproterenol in rats by means of analysis of hematological, biochemical, oxidative stress markers and histopathological parameters. METHODS: Thirty young, male, Wistar rats (145 to 230 g) were randomly allocated in two groups: Sham group, which underwent a virtual myocardial infarction induction, and the Infarction group, which underwent a myocardial infarction induction with isoproterenol. The administrations for the infarction induction were performed during two consecutive days and a 24-hour interval between them. Twenty-four hours after the last administration, rats from both groups were anesthetized and sacrificed for blood sample collection to evaluate complete blood count (CBC) and biochemical parameters (SGOT, SGPT, troponin I, urea and creatinin), obtain myocardial fragments for oxidative stress markers analyses (catalase activity and glutathione concentrations) as well as histopathological examinations. RESULTS: There were no death cases in the Sham group, while the mortality rate in the Infarction group was 25%. Myocardial infarction induction with isoproterenol raised leukocytes and neutrophils counts, SGOT, troponin I and urea concentrations, reduced catalase enzyme activity and glutathione concentrations in the myocardium and let to histopathological concentrations as well. It did not exert alterations in terms of hemoglobin, SGPT and creatinin concentrations. CONCLUSIONS: The isoproterenol-induced myocardial infarction essay in rats was adequately reproduced in our laboratory, causing alterations in hematological, biochemical, oxidative stress markers and histopathological parameters.

possible role of calcitonin gene-related peptide in estradiol cardioprotection in cases of isoproterenol-induced myocardial ischemia in rats

Relative to its metabolic requirements, heart tissue is one of the most poorly perfused in the body, and ischemia resulting from compromised coronary blood flow can have serious detrimental effects. Estrogen has been suggested to modulate vascular physiology and function from a variety of studies in cellular, animal and human models. Genetic deletion of estrogen receptor results in the development of hypertension in middle-aged male and female mice, resulting in endothelial dysfunction and oxidative stress. Calcitonin gene-related peptide [CGRP], a well characterized vasoactive neuropeptide, is a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products. It was discovered in 1982. CGRP is considered to be a neuromediator of particular importance in the cardiovascular system. Regardless of which estrogen receptor mediates cardioprotection, the mechanisms by which estrogen elicits cardioprotection in females are poorly understood. Hence, the present study was conducted in order to investigate the possible role of CGRP in cardioprotection offered by estradiol pretreatment in cases of isoproterenol-induced myocardial ischemia in rats. The present study was conducted on 24 adult female albino rats, weighing 150-200 gms, fed ad libitum, divided into 3 groups: Group [I]: 8 sham-operated rats that served as control. Group [II]: 8 rats that underwent ovarectomy [day 0] and 7 days later, they were pretreated with estradiol subcutaneously [0.25 mg/kg] for 21 day period. Group [III]: 8 rats that also underwent ovarectomy but stayed without estradiol treatment for 28 days. Group II and III rats were, thereafter, intoxicated with isoproterenol subcutaneously [85 mg/kg] for 2 consecutive days to induce myocardial ischemia. Then, all rats were killed. Blood was collected and serum was assayed for blood lipids, creatine kinase and lactate dehydrogenase activities, serum CGRP was also measured. Heart tissues were homogenized and estimation of cardiac CGRP was done. Serum creatine kinase and lactate dehydrogenase activities were significantly increased in group III rats as compared to group I and II. Serum triglycerides and total cholesterol levels also showed a significant increase in group III rats as compared to group I and II. Serum and cardiac CGRP were significantly increased in group II [estradiol-pretreated rats] as compared to group I and III. Significant positive correlation was found between serum and cardiac levels of CGRP, also between both and serum triglycerides. From the previous results, we can conclude that estradiol may exert a protective effect in cases of isoproterenol-induced myocardial ischemia in rats through increasing serum and cardiac levels of CGRP, decreasing serum lactate dehydrogenase and creatine kinase activities and lowering serum triglycerides and total cholesterol levels as compared to estradiol-untreated rats

Effect of folic acid and vitamin B[12] supplementation on isoprenaline induced myocardial infarction, endothelial dysfunction and atherothrombosis in experimental hyperhomocysteinemic rats

Elevated total plasma homocysteine [tHcy] concentration is an independent risk factor for ischemic heart disease and other vascular disorders. Treatment with vitamins [folic acid and B12] has shown to reduce plasma homocysteine level but it is not clear to what extent such treatment may reduce clinical vascular events or mortality. The aim of the present study was to evaluate hyperhomocysteinemia as a risk factor of isoprenaline induced myocardial infarction [MI], endothelial dysfunction and hypercoagulable state and to examine the effect of folic acid either alone or in combination with vitamin B[12] on the experimentally induced myocardial infarction and to evaluate the effect of such vitamin treatment on the biomarkers of endothelial dysfunction and hypercoagulable state in post-methionine load hyperhomocysteinemic rats. Hyperhomocysteinemia [Hhcy] was induced in rats by daily intake of methionine [1g/kg b.wt.] in the drinking water for 4 weeks. MI was then induced by subcutaneous injection of isoprenaline in a dose of 85mg/kg b.wt/day for two days. Serum marker enzymes, creatine kinase [CK] and lactate dehydrogenase [LDH] were measured. Lipid peroxidation was measured as malondialdehyde [MDA] and reduced glutathione [GSH] concentrations in heart tissue. Plasma concentrations of von Willebrand factor [vWF] and D-dimer as markers of endothelial dysfunction and prothrombotic state were measured either in the experimental untreated hyperhomocysteinemic rats or in the treated ones. Hhcy resulted in a significant increase in serum CK and LDH levels. Cardiac MDA was significantly increased while GSH was significantly decreased in Hhcy group compared to the normal control group, plasma concentrations of vWF and D-dimer were also significantly increased. Serum marker enzymes and markers of cardiac oxidative stress were greatly exaggerated in Hhcy rats treated with isoprenaline in comparison with isoprenaline group. Administration of folic acid [10mg/kg, b.wt orally via gavage] alone and in combination with vitamin B[12] [500 ug/kg b.wt. i.m], concurrently for 4 weeks during the induction of Hhcy markedly reduced the increase in serum CK and LDH as well as the plasma concentration of vWF and D-dimer. Cardiac MDA content was decreased while cardiac GSH was elevated in the treated group compared to untreated Hhcy rats. These results suggest that Hhcy aggravates MI via oxidative stress mechanisms and that Hhcy may impair endothelial function and increases the biomarkers of prothrombotic state Treatment with either folic acid alone or in combination with vitamin B[12] can ameliorate the detrimental effects of Hhcy, reduce the risk of MI, appears to improve endothelial dysfunction and decrease plasma concentration of biomarkers of hypercoagulability. This provides preliminary evidence that such vitamin supplementation may have beneficial cardiovascular effects. However clinical benefit of vitamin supplementation has not yet been demonstrated and clinical trials are urgently required

Caracterizaçäo funcional da hipertrofia miocárdica induzida pelo isoproterenol e de sua regressäo / Functional characterization of myocardial hypertrophy induced by isoproterenol and its regression

OBJETIVO: Analisar as disfunçöes da hipertrofia miocárdica induzida pelo isoproterenol e de sua regressäo. Coraçöes isolados hipertrofiados por isoproterenol (ISO) (8 dias) e após 22 dias de sua suspensäo (regressäo) foram distendidos. MÉTODOS: Até pressäo de repouso (Pr) de 60mmHg, analisaram-se: pressäo desenvolvida máxima (PDmáx.); estresse sistólico (sigmamáx); inclinaçäo da reta estresses/deformaçöes; constante de relaxamento; rigidez da câmara e rigidez miocárdica. RESULTADOS: Nos coraçöes hipertrofiados (H) as variaçöes de volume (deltaV) necessárias para Pr=60mmHg foram heterogêneas. Em alguns (H1; n=10) deltaV equivaleu à dos controle (C) enquanto em outros (H2; n=10) foi inferior, e também diferiram quanto ao peso seco, complacência ventricular, rigidez miocárdica, constante de relaxamento,e sigmamáx. PDmáx dos grupos H1 e H2 foram superiores às de C (n=8) e Regressäo (R) (n=8). Contudo, sigmamáx de H2 foi menor que C, H1 e R. O mecanismo de Frank-Starling foi deprimido nos coraçöes hipertrofiados. A constante de relaxamento de H2 indicou retardo no decaimento da pressäo associado a menor complacência ventricular e rigidez miocárdica acentuada. CONCLUSÄO: Hipertrofia miocárdica induzida pelo ISO näo é homogênea. Alguns coraçöes têm alteraçöes pouco expressivas; outros têm comprometimento das funçöes sistólica e diastólica. A hipertrofia miocárdica reduz a capacidade de gerar força e aprimora a capacidade em variar pressäo por aumento da relaçäo massa/volume. Há, também, comprometimento da complacência ventricular e da rigidez muscular

Mitochondrial oligomycin-sensitive ATPase during isoproterenol-induced cell injury of myocardium

En el presente trabajo se investigó la actividad enzimática de la ATPasa mitocondrial sensible a la oligomicina durante una lesión celular del miocardio inducida por el isoproterenol, usando homogenados de corazón de rata y una técnica potenciométrica. La actividad enzimática de la ATPasa mitocondrial sensible a la oligomicina, al igual que la acción inhibidora de la oligomicina sobre esta enzima, no muestra alteraciones significativas durante el tratamiento con isoproterenol. Estos resultados no concuerdan con la hipótesis sobre posibles modificaciones en la configuración activa de la ATPasa mitocondrial durante una lesión celular del miocardio inducida por el isoproterenol.

Developed pressure data may provide misinformation when used alone to evaluate systolic function in isovolumetric left ventricle preparations

We report data showing that developed pressure (DPmax) may lead to opposite conclusion with respect to maximal developed circumferential wall stress (max) when used to assess contractile function in left ventricle isovolumic preparations. Isovolumetric left ventricle preparations of rats with cardiac hypertrophy (H; N = 10) induced by isoproterenol administration showed higher DPmax (174 + ou - 14 mmHg) than control (C; N = 8) animals (155 + ou - 12 mmHg) or rats with regression (R; N = 8) of hypertrophy (144 + ouy - 11 mmHg). In contrast, the estimated max for C (145 + ou - 26 kdynes/cm2) and R (133 + ou - 17 kdynes/cm2) was higher than for H (110 + ou - 13 kdynes/cm2). According to Laplace's law, the opposite results of DPmax and max may depend on the increased mass/volume left ventricle ratio of the hypertrophied hearts, which favored pressure generation. These results clearly show that DPmax should be used with caution to analyze systolic function.

protective effect of vitamin c against isoproterenol induced myocardial damage

This study was undertaken to elucidate the protective role of vitamin C against isoproterenol induced myocardial. An infarction-like lesion was induced in a group of rats by intraperitoneal [ip] injection of a single large dose of isoproterenol [50 mg/Kg bw] 24 hours before sacrifice of animals. Another group of rats was pretreated with vitamin C either in small doses [50 mg/Kg bw] or in large doses [100 mg/Kg bw] daily for six days before isoproterenol challenge. Control rats received ip saline injection for the same period as vitamin C- treated animals. Isoproterenol had induced myocardial damage as represented by the significant increase in the Q- wave voltage and S-T segment displacement associated with significant increase in the plasma levels of lactate dehydrogenase [LDH] compared with control rats. In addition, there were significant decrease in the R-wave voltage P-R, interval, QRS-time and Q-T interval and significant increase in the heart rate. The changes in creatine kinase [CK], total cholesterol [TC], low density lipoprotein cholesterol [LDL-C] and high density lipoprotein cholesterol [HDL-C] were insignificantly different from controls. Pretreatment with vitamin C resulted in an outstanding protective effect, which was dose dependent, being more pronounced with the larger doses. This protective effect of vitamin C pointed to the potential role of this micronutrient in the prevention and promotion optimum cardiovascular health

Distúrbio de pânico e comorbidade clínica / Panic disorder and clinical comorbidity

Os autores abordam o distúrbio do pânico considerando nao só as manifestaçoes psiquiátricas mas também as possibilidades biológicas bem como as várias patologias que podem cursar com sintomatologia semelhante às crises de pânico.

Alguns aspectos da funçäo endotelial em cirurgia cardíaca / Some aspects of the endothelial function in cardiac surgery

Este estudo mostra alguns aspectos da funçäo endotelial relacionados, diretamente, com a cirurgia cardíaca: 1) Após isquemia miocárdica global seguida de reperfusäo, o endotélio coronariano perde a habilidade de expressar vasodilataçäo endotélio-dependente mediada por receptores, ao passo que o relaxamento endotélio-dependente mediado pelo cálcio ionóforo A23187 e a fosfolipasec C, que näo dependem de estimulaçäo de receptores, encontra-se inalterada. O relaxamento produzido pelo fluoreto de sódio, o qual atua através de G-proteína(s), encontra-se comprometido. Estes experimentos indicam que o comprometimento da produçäo de EDRF/NO mediada por receptores após a lesäo de reperfusäo possa ser devido a uma disfunçäo de G-proteínas que liga os receptores da célula endotelial à via da sínese de EDRF/NO; 2) Quarenta e cinco minutos de parada cardioplégica de coraçöes de cäes, pela soluçäo St. Thomas näo comprometem a produçäo de EDRF/NO em artérias epicárdicas coronárias. Estudos farmacológicos in vitro semelhantes, testando-se os efeitos da soluçäo UW, suportaram o conceito de que ela näo lesa o endotélio coronariano, sendo segura para a preservaçäo cardíaca durantes transplantes cardíacos; 3) Em segmentos de artérias coronárias, renais, femorais, e em segmentos de artéria pulmonar, a protamina induziu vasodilataçäo endotélio-dependente, mediada pela estimulaçäo da liberaçäo de EDRF/NO. Nas circulaçöes coronariana e sistêmica, ao contrário do que se verificou nos experimentos envolvendo a circulaçäo pulmonar, este efeito foi independente da presença de heparina; 4) Em 83 por cento dos ensaios biológicos, o efluente da AMI esquerda induziu um relaxamento maior do anel coronariano bioensaiado do que o efluente da AMI direita, por liberaçäo basal de EDRF/NO. Este inibe a adesividade e a agregaçäo plaquetárias e a aterogêne, contribuindo para os resultados superiores obtidos quando se utiliza esta artéria para a revascularizaçäo do miocárdi. Quando expostos à hipoxia, as atividades vasodilatadoras da AMI e da veia safena foram maiores. Esta acentuaçäo da vasodilataçäo causada pela hipóxia foi inibida pelo tratamento com a indometacina, e, rapidamente, revertida, quando se restabeleceu a normóxia.

Correlation between electrocardiographic and histopathological changes in isoprenaline-induced myocardial injury

Myocardial injury was induced in 25 dogs by infusing isoprenaline, 2-4 microgram per kg per minute for the duration of six hours. 10 dogs served as controls which received only physiological saline. Animals receiving isoprenaline 2 microgram per kg per minute were labeled as experimental group A and other receiving microgram per kg per minute as experimental group B. Histopathological observations in experimental groups A and B showed subendocardial haemorrhage in the papillary muscles and apex of left ventricle as early as two-three hours of infusion. Focal lesions characterized by congestion, dilatation and extravasation of blood was observed near necrotic myocardium. Group A animals showed only severe tachycardia while in group B myocardial infarction in 80% and only ischaemic changes in 20% of animals were observed. Out of animals in group B, 37.5% developed myocardial infarction after two hours of infusion while remaining 62.5% developed changes after four hours. Histopathological changes were very well correlated with ECG findings observed in the present study

Cardioprotective effect of captopril on the catecholamine-induced myocardial necrosis

The cardioprotective effect of captopril, a converting enzyme inhibitor, was studied on the isoprenaline-induced myocardial necrosis [M.N.] in rats. The degree of protection was assessed biochemically by measuring variations in level of serum CPK and histopathologically by estimating infarct size [I.S.]% i.e. surface area of injured myocardium to area of heart sections, after being stained with haematoxylin basic fuchcin picric acid stain. Also, injury currents in ECG were looked for. Pretreatment with captopril in a dose of 100 ug/kg i.p., 15 min. before injection of a necrotizing dose of isoprenaline [300 mg/kg] s.c., was found to be highly protective. The serum CPK and I.S. of rats pretreated with captopril were markedly decreased. Moreover, the injury currents, which were observed in ECG of rats treated with isoprenaline, disappeared in captopril treated rats. Injected 15 min. after isoprenaline, captopril was found to be protective but less effective than if it was administered before isoprenaline although used in the same dose level. The mean values of serum CPK and I.S. of post-treated rats were significantly lower than the corresponding values in isoprenaline-treated rats. Further reduction of the cardioprotective effect of captopril was noticed on increasing the post-treatment interval to 30 min. Captopril protects the heart effectively against catecholamine-induced myocardial necrosis. This protective effect proved to be time-related, the earlier the intervention, the better the results

Effect of vitamin E on the severity of myocardial infarction induced by isoproterenol.

The effect of vitamin E administration on the severity of myocardial infarction induced by isoproterenol on rats was studied. Judging from serum enzyme activity (CPK 714 micromoles; GOT 291.7 micromoles; and GPT 155.5 micromoles), mortality rate (60 to 65% survived) and histopathological observation, vitamin E has been observed to offer very little protection to the myocardium during experimental myocardial infarction when compared to control animals given isoproterenol alone (CPK 775.8 micromoles; GOT 336.2 micromoles; and GPT 168 micromoles), mortality rate (60 to 65% survived) and histopathological observation (more or less similar). The level of lipid peroxides namely hydroperoxides (control 3.15; vitamin E + iso. 14.8); conjugated diene (4.45 and 6.85) and malondialdehyde (1.22 and 2.55) in the heart were higher in the vitamin E treated animals given isoproterenol when compared to control animals given vitamin E alone. The level of cholesterol and phospholipid was more or less similar in the control animals given vitamin E alone (183.6 and 3.12) and vitamin E treated animals given isoproterenol (170.25 and 2.49), but the ratio of cholesterol to phospholipid was higher in the vitamin E treated animals given isoproterenol when compared to control animals given vitamin E alone.