Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 30
Filter
1.
Braz. j. med. biol. res ; 53(2): e9106, 2020. graf
Article in English | LILACS | ID: biblio-1055491

ABSTRACT

Reperfusion strategies in acute myocardial infarction (AMI) can cause a series of additional clinical damage, defined as myocardial ischemia/reperfusion (I/R) injury, and thus there is a need for effective therapeutic methods to attenuate I/R injury. miR-26a-5p has been proven to be an essential regulator for biological processes in different cell types. Nevertheless, the role of miR-26a-5p in myocardial I/R injury has not yet been reported. We established an I/R injury model in vitro and in vivo. In vitro, we used cardiomyocytes to simulate I/R injury using hypoxia/reoxygenation (H/R) assay. In vivo, we used C57BL/6 mice to construct I/R injury model. The infarct area was examined by TTC staining. The level of miR-26a-5p and PTEN was determined by bioinformatics methods, qRT-PCR, and western blot. In addition, the viability and apoptosis of cardiomyocytes were separately detected by MTT and flow cytometry. The targeting relationship between miR-26a-5p and PTEN was analyzed by the TargetScan website and luciferase reporter assay. I/R and H/R treatment induced myocardial tissue injury and cardiomyocyte apoptosis, respectively. The results showed that miR-26a-5p was down-regulated in myocardial I/R injury. PTEN was found to be a direct target of miR-26a-5p. Furthermore, miR-26a-5p effectively improved viability and inhibited apoptosis in cardiomyocytes upon I/R injury by inhibiting PTEN expression to activate the PI3K/AKT signaling pathway. miR-26a-5p could protect cardiomyocytes against I/R injury by regulating the PTEN/PI3K/AKT pathway, which offers a potential approach for myocardial I/R injury treatment.


Subject(s)
Animals , Rabbits , Myocardial Reperfusion Injury/metabolism , Myocardial Ischemia/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Myocytes, Cardiac/pathology , MicroRNAs/metabolism , PTEN Phosphohydrolase/metabolism , Signal Transduction , Blotting, Western , Disease Models, Animal , Proto-Oncogene Proteins c-akt/metabolism , Real-Time Polymerase Chain Reaction , Flow Cytometry , Mice, Inbred C57BL
2.
Rev. bras. cir. cardiovasc ; 33(3): 291-302, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-958412

ABSTRACT

Abstract The heat shock proteins are endogenous proteins with the ability to act as molecular chaperones. Methods that provide cell protection by way of some damage can positively influence the results of surgery. The present review summarizes current knowledge concerning the cardioprotective role of the heat shock proteins as occurs in heart damage, including relevant information about the stresses that regulate the expression of these proteins and their potential role as biomarkers of heart disease.


Subject(s)
Humans , Myocardial Ischemia/metabolism , Myocytes, Cardiac/physiology , Cardiac Surgical Procedures , Heat-Shock Proteins/physiology , Biomarkers/metabolism , Heat-Shock Proteins/analysis , Myocardium/metabolism , Myocardium/chemistry
3.
Braz. j. med. biol. res ; 51(6): e6555, 2018. graf
Article in English | LILACS | ID: biblio-889109

ABSTRACT

Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of cardiovascular diseases, especially in myocardial infarction and ischemia/reperfusion (I/R). However, the underlying molecular mechanism remains unclear. In this study, we determined the role and the possible underlying molecular mechanism of lncRNA-ROR in myocardial I/R injury. H9c2 cells and human cardiomyocytes (HCM) were subjected to either hypoxia/reoxygenation (H/R), I/R or normal conditions (normoxia). The expression levels of lncRNA-ROR were detected in serum of myocardial I/R injury patients, H9c2 cells, and HCM by qRT-PCR. Then, levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) were measured by kits. Cell viability, apoptosis, apoptosis-associated factors, and p38/MAPK pathway were examined by MTT, flow cytometry, and western blot assays. Furthermore, reactive oxygen species (ROS) production was determined by H2DCF-DA and MitoSOX Red probes with flow cytometry. NADPH oxidase activity and NOX2 protein levels were measured by lucigenin chemiluminescence and western blot. Results showed that lncRNA-ROR expression was increased in I/R patients and in H/R treatment of H9c2 cells and HCM. Moreover, lncRNA-ROR significantly promoted H/R-induced myocardial injury via stimulating release of LDH, MDA, SOD, and GSH-PX. Furthermore, lncRNA-ROR decreased cell viability, increased apoptosis, and regulated expression of apoptosis-associated factors. Additionally, lncRNA-ROR increased phosphorylation of p38 and ERK1/2 expression and inhibition of p38/MAPK, and rescued lncRNA-ROR-induced cell injury in H9c2 cells and HCM. ROS production, NADPH oxidase activity, and NOX2 protein levels were promoted by lncRNA-ROR. These data suggested that lncRNA-ROR acted as a therapeutic agent for the treatment of myocardial I/R injury.


Subject(s)
Humans , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/metabolism , RNA, Long Noncoding/metabolism , Apoptosis , Blotting, Western , Cell Survival , Glutathione Peroxidase/metabolism , Hydro-Lyases/metabolism , Malondialdehyde/metabolism , Myocardial Ischemia/genetics , Myocardial Reperfusion Injury/genetics , Myocytes, Cardiac , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding/genetics , Signal Transduction , Superoxide Dismutase/metabolism , Transfection
4.
An. acad. bras. ciênc ; 89(3): 1683-1690, July-Sept. 2017. graf
Article in English | LILACS | ID: biblio-886764

ABSTRACT

ABSTRACT Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique. The animals were monitored during surgery by pH and lactate levels. Transcription analysis of the pyruvate kinase, lactate dehydrogenase and phosphoenolpyruvate carboxykinase enzymes were performed by qRT-PCR, and glycogen quantification was determined enzymatically. Pyruvate kinase transcription increased during ischemia, followed by glycogen consumption content. The gluconeogenesis increased in control and ischemia moments, suggesting a relationship between gluconeogenesis and glycogen metabolism. This result shows the significant contribution of these substrates in the organ energy supply and demonstrates the capacity of the heart to adapt the metabolism after this injury, sustaining the homeostasis during short-term myocardial ischemia.


Subject(s)
Animals , Male , Rabbits , Myocardial Reperfusion Injury/metabolism , Myocardial Ischemia/metabolism , Gluconeogenesis/physiology , Glycogen/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocardial Ischemia/physiopathology , Disease Models, Animal
5.
Braz. j. med. biol. res ; 50(4): e5861, 2017. tab, graf
Article in English | LILACS | ID: biblio-839274

ABSTRACT

Myocardial ischemia is a major cause of death and remains a disease with extremely deficient clinical therapies and a major problem worldwide. Cold inducible RNA-binding protein (CIRBP) is reported to be involved in multiple pathological processes, including myocardial ischemia. However, the molecular mechanisms of myocardial ischemia remain elusive. Here, we first overexpressed CIRBP by transfection of pc-CIRBP (pcDNA3.1 containing coding sequenced for CIRBP) and silenced CIRBP by transfection of small interfering RNA targeting CIRBP (siCIRBP). pcDNA3.1 and the negative control of siCIRBP (siNC) were transfected into H9C2 cells to act as controls. We then constructed a cell model of myocardial ischemia through culturing cells in serum-free medium with hypoxia in H9C2 cells. Subsequently, AlamarBlue assay, flow cytometry and western blot analysis were used, respectively, to assess cell viability, reactive oxygen species (ROS) level and apoptosis, and expression levels of IκBα, p65 and Bcl-3. We demonstrated that CIRBP overexpression promoted cell proliferation (P<0.001), inhibited cell apoptosis (P<0.05), reduced ROS level (P<0.001), down-regulated phosphorylated levels of IκBα and p65 (P<0.01 or P<0.001), and up-regulated expression of Bcl-3 (P<0.001) in H9C2 cells with myocardial ischemia. The influence of CIRBP knockdown yielded opposite results. Our study revealed that CIRBP could protect H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.


Subject(s)
Animals , Rats , Myocardial Ischemia/metabolism , Myocardial Ischemia/prevention & control , NF-kappa B/antagonists & inhibitors , Protective Agents/pharmacology , RNA-Binding Proteins/pharmacology , Apoptosis/drug effects , Blotting, Western , Cell Proliferation/drug effects , Cell Survival , Cells, Cultured , Flow Cytometry , Gene Expression Regulation , NF-kappa B/metabolism , Reactive Oxygen Species/analysis , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , RNA, Small Interfering , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Time Factors , Transfection/methods
6.
Arq. bras. cardiol ; 107(4): 339-347, Oct. 2016. tab, graf
Article in English | LILACS | ID: biblio-827852

ABSTRACT

Abstract Background: Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. Objective: We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Method: Rats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx). Results: Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Conclusion: Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart.


Resumo Fundamentos: A doença arterial coronariana é duas a três vezes mais comum em indivíduos diabéticos. O nitrato/nitrito dietético tem efeitos benéficos tanto para o diabetes quanto para a doença cardiovascular, assim como efeitos protetores contra a lesão de isquemia-reperfusão (IR) miocárdica em animais saudáveis. Porém, os efeitos do nitrato na lesão de IR miocárdica em ratos diabéticos ainda não foram investigados. Objetivos: Foram examinados os efeitos sobre a lesão de IR miocárdica da adição de nitrato à dieta de ratos com diabetes mellitus tipo 2 induzido por estreptozotocina-nicotinamida. Métodos: Os ratos foram divididos em quatro grupos (n = 7 em cada grupo): controle, controle+nitrato, diabetes e diabetes+nitrato. O diabetes foi induzido nos animais por injeção de estreptozotocina e nicotinamida. Nitrato (nitrato de sódio) foi adicionado à água de beber (100 mg/L) por 2 meses. Os corações foram perfundidos em sistema de Langendorff aos 2 meses e avaliados antes (basal) e após IR miocárdica em relação aos seguintes parâmetros: pressão desenvolvida no ventrículo esquerdo (PDVE), taxas máximas de variação positiva e negativa da pressão ventricular esquerda (±dP/dt), expressão do RNAm da óxido nítrico (NO) sintase (NOS) endotelial (eNOS) e da NOS induzível (iNOS), além de níveis de malondialdeído (MDA) e metabólitos do óxido nítrico (NOx). Resultados: A recuperação da PDVE e ±dP/dt foi inferior nos ratos diabéticos versus controles, mas quase normalizou após ingestão de nitrato. Ratos diabéticos apresentaram expressão diminuída de eNOS e aumentada de iNOS tanto no estado basal quanto após IR, e o consumo dietético de nitrato restaurou estes valores para o estado normal após a IR. O nível de NOx cardíaco foi menor nos ratos diabéticos em comparação aos controles no momento basal, mas foi superior após a IR. Ratos diabéticos apresentaram níveis mais elevados de MDA tanto no estado basal quanto após IR que, juntamente com os níveis cardíacos de NOx, reduziram após consumo dietético do nitrato. Conclusões: O consumo dietético de nitrato por ratos diabéticos ofereceu cardioproteção contra a lesão de IR através da regulação da expressão de eNOS e iNOS e inibição da peroxidação lipídica no coração.


Subject(s)
Animals , Male , Cardiotonic Agents/therapeutic use , Myocardial Reperfusion Injury/prevention & control , Myocardial Ischemia/prevention & control , Diabetes Mellitus, Type 2/complications , Nitrates/therapeutic use , Lipid Peroxidation/physiology , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/metabolism , Reproducibility of Results , Treatment Outcome , Myocardial Ischemia/physiopathology , Myocardial Ischemia/metabolism , Streptozocin , Coronary Vessels/physiopathology , Coronary Vessels/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/metabolism , Hemodynamics , Malondialdehyde/analysis
7.
Arch. endocrinol. metab. (Online) ; 60(1): 79-84, Feb. 2016. tab, graf
Article in English | LILACS | ID: lil-774624

ABSTRACT

SUMMARY The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.


Subject(s)
Humans , Male , Middle Aged , /complications , Hypogonadism/complications , Myocardial Ischemia/complications , Osteoporosis/complications , Testis/abnormalities , /metabolism , Hypogonadism , Myocardial Ischemia/metabolism , Osteoporosis/metabolism , Osteoporosis , Risk Factors , Testis/metabolism , Testis , Testosterone/blood , Thyrotropin/blood
8.
Biomédica (Bogotá) ; 34(3): 387-402, July-Sept. 2014. ilus
Article in Spanish | LILACS | ID: lil-726799

ABSTRACT

Introducción. El factor de transcripción asociado a la microftalmia ( Microphtalmia-Associated Transcription Factor , MITF) regula la expresión de genes específicos, pero no se conoce su expresión y su función a nivel cardiaco. Objetivos. Identificar la expresión del MITF en corazón y en cardiomiocitos aislados de cobayo, describir los cambios morfológicos asociados con su disminución y evaluar los niveles relativos de su expresión en cardiomiocitos aislados en condiciones de preacondicionamiento isquémico. Materiales y métodos. El análisis de la expresión relativa de la isoforma específica de tejido cardiaco ( heart-type MITF, MITF-H), se determinó mediante reacción en cadena de la polimerasa (PCR) en tiempo real semicuantitativa, secuenciación y Western blot . La disminución del ARNm del MITF se indujo con un ARN pequeño de interferencia ( short hairpin RNA interference , shRNAi) específico. El tamaño, el diámetro y el número de fibras musculares se evaluaron por observación directa con microscopía de luz. Resultados. Se amplificó un fragmento de 281 pb de ADNc; el análisis de la secuencia confirmó la identidad del exón 1 y la isoforma H del MITF. La interferencia del ARNm del MITF se asoció con un mayor índice cardiaco (peso corazón/peso corporal: 5,46 x 10 -3 Vs. 4,6 x 10 -3 ) y un incremento del diámetro de las fibras cardiacas (50,2±16 µm Vs. 38,7±14,7 µm; p<0,05, n=150). En los cardiomiocitos aislados en condiciones de preacondicionamiento isquémico, se observó una expresión relativa del MITF-H mayor que en los miocitos en normoxia y expuestos a lesión por isquemia simulada (80 y 100 veces más, n=5, p<0,05, n=3). Conclusión. Los resultados sugieren que el MITF-H podría estar involucrado en la hipertrofia, la respuesta al estrés por isquemia y la supervivencia de cardiomiocitos de cobayo.


Introduction: The microphthalmia -associated transcription factor ( MITF ) regulates the expression of specific genes and its cardiac expression and function is not known. Objectives: To identify the expression of MITF in hearts and isolated cardiomyocytes from Guinea pigs, to describe morphological changes associated with mRNA interference of MITF and to evaluate their relative changes in expression in isolated cardiomyocytes under ischemic preconditioning. Materials and methods: The cardiac specific isoform, MITF-H, and relative expression level analysis, was determined by semi-quantitative real time PCR, sequencing and Western blotting. Reduction of mRNA-MITF-H was induced by transduction of specific-MITF-shRNAi interference. The cardiac morphological changes, diameter and number of cardiac fibers were evaluated by direct observation and light microscopy. Results: A cDNA fragment of 281 bp was amplified from heart and isolated ventricular cardiac myocytes. Sequence analysis confirmed the identity of the isoform MITF-H, exon 1. The MITF silencing was associated with an increase in cardiac index (heart weight/body weight vs . 5.46 x 10 -3 vs 4.6 x 10 -3 ) and higher diameter of cardiac fibers (50.2±16 µ m vs 38,7±14,7 µ m p<0.05, n=150). In isolated cardiac myocytes under ischemic preconditioning we observed a higher relative expression compared with that measured in myocytes exposed to normoxia and simulated ischemia (eighty and one hundred times, p <0.05, n = 5). Conclusion. The results suggest that MITF-H isoform may be involved in Guinea pig cardiac hypertrophy, response to stress by ischemia and cardiomyocytes survival.


Subject(s)
Animals , Female , Guinea Pigs , Cardiomyopathy, Hypertrophic/metabolism , Microphthalmia-Associated Transcription Factor/physiology , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Amino Acid Sequence , Base Sequence , Cell Survival , Cells, Cultured , Cardiomyopathy, Hypertrophic/genetics , DNA, Complementary/genetics , Gene Expression Regulation , Ischemic Preconditioning, Myocardial , Molecular Sequence Data , Microphthalmia-Associated Transcription Factor/antagonists & inhibitors , Microphthalmia-Associated Transcription Factor/biosynthesis , Microphthalmia-Associated Transcription Factor/genetics , Myocardial Ischemia/genetics , Myocardial Ischemia/metabolism , Myocytes, Cardiac/pathology , Oxygen/pharmacology , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , Protein Isoforms/physiology , RNA Interference , RNA, Small Interfering/pharmacology , Sequence Alignment , Sequence Homology
9.
Indian J Biochem Biophys ; 2013 Apr; 50(2): 99-104
Article in English | IMSEAR | ID: sea-147292

ABSTRACT

Increased production of oxygen free radicals and decreased oxidant capacity occur in coronary artery diseases (CAD). This pro-oxidant shift in intracellular redox state may induce cell death by either direct cell membrane damage by lipid peroxidation or apoptosis through activation of transcription factors. These changes occur not only in cardiomyocytes, but also in cardiac sympathetic nerves, which are very sensitive to oxidative damage. Patients with heart failure encounter reduced peripheral blood flow at rest, during exercise and in response to endothelium-dependent vasodilators. Current treatments of cardiomyopathy, a degenerative condition of the myocardium frequently associated with heart failure have done little to enhance patient survival. Decreased myocardial contractility and altered regulation of peripheral circulation along with oxidative conditions are important contributors to the symptoms and prognosis of the disease process. Nitric oxide formed from L-arginine (2-amino-5 guanidinovaleric acid) metabolism in endothelial cells contributes to regulation of blood flow under these conditions. L-Arginine is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. In the present study, we investigated the effect of oral administration of L-arginine (3 g/day) on the intracellular redox status of the patients of ischemic cardiomyopathy aged 45-60 yrs. The enzymatic and non-enzymatic antioxidant parameters like superoxide dismutase, catalase, total thiols (TSH) and ascorbic acid along with pro-oxidant parameters, such as xanthine oxidase, as well as index of oxidative stress as protein carbonyl content and malondialdehyde (a marker of lipid peroxidation) were investigated in the plasma and RBC lysate. L-Arginine (3 g/day) administration was found to improve the levels of these parameters in the patients and regulate the blood flow, as evident by the improved blood pressure of the patients. Thus, it is inferred that L-arginine attenuates the oxidative stress conditions along with maintaining the blood pressure rate of patients suffering from cardiomyopathy.


Subject(s)
Antioxidants/metabolism , Arginine/metabolism , Ascorbic Acid/metabolism , Cardiomyopathies/metabolism , Catalase/metabolism , Coronary Artery Disease/metabolism , Female , Free Radicals , Humans , Male , Middle Aged , Models, Biological , Myocardial Ischemia/metabolism , Oxidants , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism , Thyrotropin/metabolism , Xanthine Oxidase/metabolism
10.
Rev. bras. cir. cardiovasc ; 26(3): 433-439, jul.-set. 2011.
Article in English | LILACS | ID: lil-624526

ABSTRACT

OBJECTIVE: To evaluate pantoprazole effect in the functional recovery of isolated hearts of rats, submitted to ischemia and reperfusion with and without ischemic preconditioning. METHODS: In four groups of eight Wistar breed rats, the hearts were removed after anesthesia and perfused with Krebs-Henseleit solution (95% O2, 5% CO2, 37ºC). GI, GII, GIII and GIV hearts were submitted to ischemia (20 min) and reperfusion (30 min). In GII and GIV, preconditioning was performed with 5 min of ischemia and 5 min of reperfusion before 20 min of the ischemia period induction. In GIII and GIV pantoprazole 100 mg was done before a 20 min-period of ischemia induction. Heart Rate (HR), Coronary Flow (CoF), Systolic Pressure (SP), +dP/dt and -dP/dt were registered before (t0) and after reperfusion (t30). Kruskal-Wallis (P<0.05) test was used. RESULTS: There were no differences (P>0.05) between groups among HR and CoF values. Differences occurred between groups, I and II, III and IV at t30 with SP reduced for 32% mean value in GI, 65% GII, 65% GIII, and 73% GIV; The t30 + dP/dtmax were 34% in GI, 61% GII, 63% GIII and 72% GIV. The t30 -dP/dtmax were GI 28%, GII 63%, GIII 75 % and GIV 75%; (P<0.05). There were no significant differences in the SP, +dP/dtmax, and -dP/dtmax between Groups II, III and IV results. CONCLUSIONS: The administration of pantoprazole before induction of ischemia significantly protected the myocardial functional recovery with the results of SP, + dP / dtmax and dP/dtmax similar to the ischemic preconditioning against ischemia-reperfusion.


OBJETIVO: Avaliar o efeito do pantoprazol na recuperação funcional de corações isolados de ratos submetidos à isquemia e reperfusão com e sem pré-condicionamento isquêmico. MÉTODOS: Em quatro grupos de oito ratos Wistar, após anestesia os corações foram removidos e perfundidos com Krebs-Henseleit (95% O2, 5% CO2, 37ºC). Os corações de GI, GII, GIII e GIV foram submetidos a 20' de isquemia e 30'de reperfusão. Em GII e GIV realizou-se pré condicionamento com 5' de isquemia e 5' de reperfusão antes dos 20' de isquemia. Em GIII e GIV, pantoprazol 100mcg foram injetados imediatamente antes dos 20' de isquemia. Frequência cardíaca (FC), Fluxo Coronariano (FCo), Pressão Sistólica (PS), + dP/dt e -dP/dt foram registrados em (T0) e (t30). Estatística: Kruskal-Wallis (P <0,05). RESULTADOS: Não houve diferenças (P> 0,05) entre grupos nos valores de FC e de CFo. Diferenças (P <0,05) ocorreram entre GI e GII, GIII e GIV, com PS t30 reduzida para 32% GI, 65% GII, 65% GIII e 73% GIV. Em t30 + dP/dtmax 34% GI, 61% GII, 63% GIII e 72% GIV. A -dP/dtmax t30 GI 28%, GII 63%, GIII 75% e GIV 75%. Não houve diferença estatística (P< 0,05) nos valores de PS, +dP/dtmax e -dP/dtmax entre os GII, GIII e GIV. CONCLUSÕES: A administração do pantoprazol antes da indução da isquemia protegeu significativamente a recuperação funcional miocárdica com resultados de SP, +dP/ dtmax e -dP/dtmax semelhantes aos do pré-condicionamento isquêmico contra lesão de isquemia-reperfusão.


Subject(s)
Animals , Rats , Enzyme Inhibitors/pharmacology , Ischemic Preconditioning, Myocardial , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/prevention & control , /pharmacology , Enzyme Inhibitors/adverse effects , Heart Rate/drug effects , Ischemic Preconditioning, Myocardial/methods , Models, Animal , Myocardial Contraction/drug effects , Random Allocation , Rats, Wistar , Recovery of Function/drug effects , /adverse effects
11.
Braz. j. med. biol. res ; 44(9): 890-898, Sept. 2011. ilus
Article in English | LILACS | ID: lil-599672

ABSTRACT

Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI) has decreased in the last decades. However, the incidence of heart failure (HF) in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.


Subject(s)
Humans , Heart Failure/etiology , Heart/physiopathology , Myocardial Infarction/complications , Myocardial Ischemia/physiopathology , Adrenergic Neurons/physiology , Aldosterone/physiology , Angiotensins/metabolism , Apoptosis/physiology , Arrhythmias, Cardiac/etiology , Heart Failure/prevention & control , Inflammation Mediators/metabolism , Myocardial Ischemia/metabolism , Myocardium/metabolism , Myocytes, Cardiac/physiology , Renin-Angiotensin System/physiology , Sympathetic Nervous System/physiology , Time Factors
12.
Indian J Biochem Biophys ; 2009 Dec; 46(6): 498-502
Article in English | IMSEAR | ID: sea-135233

ABSTRACT

Increased production of free radicals under oxidative stress conditions plays a vital role in the impairment of endothelial function and also in the pathogenesis of ischemic heart diseases. Ischemia, followed by reperfusion, leads to the exacerbated formation of oxy- free radicals. These reactive oxygen species through a chain of reactions damage the cardiomyocytes and cause more injury to the myocardium. L-Arginine is reported to act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and these roles of L-arginine are mediated by nitric oxide (NO). In the present study, the effect of oral administration of L-arginine (3 g/day for 7 days) on some antioxidant enzymes, total thiols, lipid peroxidation measured as malondialdehyde (MDA), and plasma ascorbate levels in myocardial ischemic patients was investigated. We observed an increase in the activity of superoxide dismutase (SOD), total thiols (T-SH) and plasma ascorbate levels and a decrease in the activity of xanthine oxidase (XO), MDA levels, carbonyl content and serum cholesterol in the patients on oral administration of L-arginine. The present study demonstrates that L-arginine administration may be beneficial to patients with myocardial ischemic disorders, such as acute myocardial infarction and acute angina.


Subject(s)
Adult , Aged , Arginine/administration & dosage , Arginine/pharmacology , Arginine/therapeutic use , Ascorbic Acid/metabolism , Case-Control Studies , Cholesterol/blood , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/pharmacology , Free Radical Scavengers/therapeutic use , Humans , Malondialdehyde/metabolism , Middle Aged , Myocardial Ischemia/blood , Myocardial Ischemia/drug therapy , Myocardial Ischemia/enzymology , Myocardial Ischemia/metabolism , Oxidants/metabolism , Sulfhydryl Compounds/metabolism , Superoxide Dismutase/metabolism , Xanthine Oxidase/metabolism
13.
Medical Forum Monthly. 2009; 20 (12): 57-59
in English | IMEMR | ID: emr-111265

ABSTRACT

To determine the frequency of hyperuricemia, as a risk factor, in patients with ischemic heart disease in our setup. This prospective and observational study was carried out in the Departments of cardiology, medical unit III and pathology, Peoples Medical College and Hospital, Nawabshah from 15[th] January 2007 to 15[th] July 2007. Fifty patients, of any age and of either sex, diagnosed on ECG as ischemic heart disease [IHD] were selected and compared with serum uric acid [SUA] levels and age, sex, approximately body mass index [BMI] matched healthy controls. SUA was measured on 3[rd] day of admission by using enzyme uricase method on CLINIKON photometer 5010. Hyperuricemia was found in 27 out of 50 IHD patients and in 5 out of 50 controls; therefore a highly significant association was observed. Mean SUA level was 7.21 +/- 2.14 in patients with ischemic heart disease and 5.38 +/- 1.26 was found in healthy control subject. The difference between these two means was highly significant [P<0.0001]. Hyperuncemia significantly associates with IHD. It does not cause t IHD, neither is an independent risk factor but it only accelerates the process of atherosclerosis which can worsen the preexisting IHD


Subject(s)
Humans , Myocardial Ischemia/metabolism , Hyperuricemia/epidemiology , Uric Acid , Body Mass Index , Prospective Studies , Risk Factors
14.
Rev. bras. cir. cardiovasc ; 23(2): 224-234, abr.-jun. 2008. ilus, graf
Article in English, Portuguese | LILACS | ID: lil-492975

ABSTRACT

OBJETIVO: Verificar, em modelo experimental de coração isolado de suínos, se a associação da trimetazidina à solução cardioplégica promove melhora no desempenho do coração. MÉTODOS: O modelo experimental utilizou suínos Large-White, com coração isolado perfundido por suporte de outro animal em modo de execução de trabalho ("working heart state"). Foram divididos em três grupos (n = 6), submetidos a isquemia regional seguida de isquemia global, que recebiam um dos três tratamentos: solução St Thomas (ST), solução St Thomas acrescida de trimetazidina (TMZ) e grupo controle (Co). Durante período de reperfusão, aos 30, 60 e 90 minutos, foram medidos parâmetros hemodinâmicos de contratilidade e metabólicos, obtendo-se assim a elastância máxima (Emáx), o índice de trabalho sistólico pré-recrutável (PRSW), "dureza" do ventrículo (EDPRV), fluxo coronariano, consumo de oxigênio e dosagens de lactato e glicose. Os resultados foram analisados estatisticamente. RESULTADOS: Em relação aos parâmetros hemodinâmicos de contratilidade, não houve diferença estatística significante entre os três grupos. Houve produção crescente de lactato nos três grupos de forma uniforme quanto maior o tempo de reperfusão. O fluxo coronariano, o consumo de oxigênio e o consumo de glicose tiveram grande variação entre os diferentes tempos medidos, mas sem diferença entre os três tratamentos. O peso final do ventrículo esquerdo foi significativamente menor no grupo trimetazidina (TMZ) do que nos demais. CONCLUSÃO: A administração da trimetazidina associada como adjuvante à solução cardioplégica, sem pré-tratamento, não demonstrou benefício hemodinâmico ou metabólico em modelo experimental "working heart" de coração isolado em porcos.


OBJECTIVE: The aim of this study is to verify in an isolated working heart swine model if the acute administration of trimetazidine to cardioplegia, without pre=treatment improves heart performance. METHODS: Eighteen pairs of swines were used in this working heart model, divided into three groups (n = 6) that underwent regional and global ischemia. Each group was selected to a different treatment: St Thomas cardioplegia (ST), St Thomas enriched with trimetazidine (TMZ) and control group (Co). Data was collected during reperfusion period at 30, 60 and 90 minutes. Hemodinamic parameters such as elastance contractility index (Emax), preload recruitable stroke work relationship (PRSW) and heart "stiffness" (EDPVR) were measured. Other data included coronary flow, lactate, oxygen and glucose consumption. Results were statistically analyzed. RESULTS: All contractility data were not significantly different among three groups. Lactate became constantly higher according to time uniformly in all three groups. Coronary flow, glucose consumption and oxygen consumption presented large variations during time periods but according to treatments showed no statistical differences in all three groups. Left ventricle final weight was significantly lower in trimetazidine group compared to both other groups. CONCLUSION: Administration of trimetazidine enhanced cardioplegia, without pre-treatment, showed no hemodinamic or metabolic improvement in swine isolated working heart model.


Subject(s)
Animals , Female , Cardioplegic Solutions/pharmacology , Models, Cardiovascular , Myocardial Contraction/drug effects , Myocardial Ischemia/metabolism , Trimetazidine/pharmacology , Analysis of Variance , Bicarbonates/pharmacology , Calcium Chloride/pharmacology , Hemodynamics/drug effects , Lactic Acid/metabolism , Models, Animal , Myocardial Reperfusion , Magnesium/pharmacology , Myocardial Contraction/physiology , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , Perfusion/methods , Potassium Chloride/pharmacology , Swine , Sodium Chloride/pharmacology , Time Factors
15.
Article in English | IMSEAR | ID: sea-46886

ABSTRACT

Disturbed lipid profile is one of the most important and potent risk factors in ischemic heart disease (IHD). In recent years, it has been demonstrated that raised oxidative stress promotes several undesirable pathways including the formation of oxidised LDL (O-LDL) and oxidized cholesterol which encourages cholesterol accumulation in arterial tissues. We, therefore, aimed to ascertain the redox balance by measuring oxidative stress (OS) and total antioxidant activity (TAA) along with lipid profile to determine their possible association with IHD. Our study group comprised of 28 confirmed cases of IHD. The inclusion criterion was history of chest pain, ischemic changes in the ECG and good left ventricular (LV) function. Patients with diabetes mellitus, poor LV function, previous infarct and valvular heart disease were excluded. Lipid profile, plasma thiobarbituric acid reactive substances (TBARS), plasma total antioxidant activity (TAA) and urinary TBARS were estimated in these patients by standard procedures and the values were compared with 30 age, sex and socioeconomically matched normal healthy control subjects. Body mass index (BMI) and waist/hip ratio (W/H ratio) was also noted in both the groups. Lipid profile and OS (TBARS levels) were significantly raised in IHD patients. Though statistically not significant but TAA tended to be lower and urinary TBARS levels tended to be higher in patients. BMI, W/H ratio, smoking and alcohol did not show discernible association with lipid profile, OS or TAA. OS is significantly raised in majority of IHD patients. The non association of BMI, W/H ratio, smoking and alcohol with lipid profile, OS and TAA suggest that there are other risk factors which primarily contribute to the initiation and progression of IHD.


Subject(s)
Antioxidants/metabolism , Female , Humans , Lipids/blood , Male , Middle Aged , Myocardial Ischemia/metabolism , Nepal , Oxidative Stress , Thiobarbituric Acid Reactive Substances
16.
Braz. j. med. biol. res ; 38(3): 345-352, mar. 2005. ilus
Article in English | LILACS | ID: lil-394809

ABSTRACT

Mitochondrial ion transport, oxidative phosphorylation, redox balance, and physical integrity are key factors in tissue survival following potentially damaging conditions such as ischemia/reperfusion. Recent research has demonstrated that pharmacologically activated inner mitochondrial membrane ATP-sensitive K+ channels (mitoK ATP) are strongly cardioprotective under these conditions. Furthermore, mitoK ATP are physiologically activated during ischemic preconditioning, a procedure which protects against ischemic damage. In this review, we discuss mechanisms by which mitoK ATP may be activated during preconditioning and the mitochondrial and cellular consequences of this activation, focusing on end-effects which may promote ischemic protection. These effects include decreased loss of tissue ATP through reverse activity of ATP synthase due to increased mitochondrial matrix volumes and lower transport of adenine nucleotides into the matrix. MitoK ATP also decreases the release of mitochondrial reactive oxygen species by promoting mild uncoupling in concert with K+/H+ exchange. Finally, mitoK ATP activity may inhibit mitochondrial Ca2+ uptake during ischemia, which, together with decreased reactive oxygen release, can prevent mitochondrial permeability transition, loss of organelle function, and loss of physical integrity. We discuss how mitochondrial redox status, K+ transport, Ca2+ transport, and permeability transitions are interrelated during ischemia/reperfusion and are determinant factors regarding the extent of tissue damage.


Subject(s)
Humans , Mitochondria, Heart/metabolism , Myocardial Reperfusion Injury/metabolism , Potassium Channels/physiology , Biological Transport , Ischemic Preconditioning, Myocardial , Membrane Potentials/physiology , Myocardial Ischemia/metabolism , Oxidative Stress , Phosphorylation , Potassium Channels/metabolism , Potassium/metabolism
17.
Arch. cardiol. Méx ; 74(1): 68-79, mar. 2004. ilus, tab
Article in Spanish | LILACS | ID: lil-631856

ABSTRACT

En esta segunda parte de nuestra revisión se propone a la solución polarizante como una alternativa más, además de otras ya existentes, para el mantenimiento de las células cardíacas durante un infarto, apoyado en el cambio metabólico cardíaco durante la hipoxia.


Based on the cardiac metabolic changes during hypoxia, in this second part of our review we propose, the polarizing solution as an alternative for the maintenance of the cardiac cells during an infarction, in conjunction with other alternative therapies.


Subject(s)
Animals , Humans , Rats , Hypoxia/metabolism , Glucose/therapeutic use , Insulin/therapeutic use , Monosaccharide Transport Proteins/therapeutic use , Myocardial Ischemia/metabolism , Myocardium/metabolism , Potassium/therapeutic use , Clinical Trials as Topic , Myocardial Ischemia/drug therapy
18.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 13(5): 693-706, set.-out. 2003. ilus
Article in Portuguese | LILACS | ID: lil-364543

ABSTRACT

Ca2+ é um importante mensageiro intracelular e, no coração, o aumento da concentração citosólica de Ca2+ ([Ca2+]i) é o elo que acopla a excitação elétrica ao processo de contração. A maior parte do Ca2+ ativador da contração é liberada pelo retículo sarcoplasmático em resposta ao influxo de Ca2+ durante o potencial de ação, ao passo que, durante o relaxamento, a redução de [Ca2+]i é efetuada pela captação de Ca2+ pelo retículo sarcoplasmático e, em menor grau, por efluxo eletrogênico de Ca2+ por meio do trocador Na+-Ca2+. A liberação diastólica de grande quantidade de Ca2+ do retículo sarcoplasmático (que ocorre durante a sobrecarga celular de Ca2+ e/ou estimulação beta-adrenérgica de células miocárdicas) ativa correntes de membrana dependentes de Ca2+ (por exemplo, via o trocador Na+-Ca2+), que podem gerar pós-despolarizações. Caso o potencial de membrana atinja o limiar de excitação, ocorre um potencial de ação espontâneo, podendo resultar em automatismo miocárdico ectópico. É interessante observar que um mecanismo semelhante é utilizado por células marcapasso atriais em condições fisiológicas para desenvolver despolarização diastólica e, assim, atividade elétrica espontânea. Nesta breve revisão, serão apresentados alguns dos mecanismos celulares que podem favorecer sobrecarga de Ca2+i e desenvolvimento de atividade elétrica disparada em células miocárdicas, especialmente nas condições de isquemia miocárdica aguda e insuficiência cardíaca.


Subject(s)
Humans , Calcium Metabolism Disorders/complications , Calcium Metabolism Disorders/metabolism , Heart Failure/etiology , Heart Failure/metabolism , Myocardial Ischemia/complications , Myocardial Ischemia/metabolism , Sodium-Calcium Exchanger
19.
Rev. chil. cardiol ; 18(2): 69-76, mayo-jul. 1999. ilus, tab
Article in Spanish | LILACS | ID: lil-277189

ABSTRACT

La terapia con solución de glucosa insulina y potasio en el infarto o solución GIK fue inicialmente utilizada por Sodi-Pallares. Desde entonces muchos trabajos con esta solución han sido publicados con resultados disímiles. Sin embargo el resultado de un meta-análisis reciente, que incluye sólo trabajos randomizados con dosis adecuadas de GIK, parece confirmar la disminución de la mortalidad asociada a solución GIK. Para comprender mejor los fundamentos y posibles mecanismos de beneficio con el empleo de la solución GIK en el infarto del miocardio, revisaremos primero el metabolismo miocárdico normal y en condiciones de isquemia, luego el daño por reperfusión post infarto y los efectos de la solución GIK en el miocardio. Por último, analizaremos las experiencias clínicas publicadas con esta terapia


Subject(s)
Humans , Glucose/pharmacology , Insulin/pharmacology , Myocardial Infarction/drug therapy , Potassium/pharmacology , Myocardial Stunning/drug therapy , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL