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1.
Arq. bras. cardiol ; 114(2): 234-242, Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088869

ABSTRACT

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.


Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.


Subject(s)
Animals , Male , DNA Damage/genetics , Heart Failure/genetics , Reference Values , Rats, Wistar , Oxidative Stress , Muscle, Skeletal/pathology , Comet Assay , Single-Cell Analysis , Heart Failure/pathology , Heart Ventricles/pathology , Hemodynamics , Liver/pathology , Lung/pathology , Myocardial Infarction/genetics , Myocardial Infarction/pathology
2.
Acta cir. bras ; 33(12): 1067-1077, Dec. 2018. graf
Article in English | LILACS | ID: biblio-973486

ABSTRACT

Abstract Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.


Subject(s)
Animals , Male , Alprostadil/pharmacology , Myocardial Reperfusion Injury/prevention & control , Nitric Oxide Synthase Type III/metabolism , Antioxidants/pharmacology , Superoxide Dismutase/analysis , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Catalase/analysis , Random Allocation , Blotting, Western , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Troponin T/drug effects , Troponin T/blood , Enzyme Activation/drug effects , Creatine Kinase, MB Form/drug effects , Creatine Kinase, MB Form/blood , Heart Ventricles/drug effects , Heart Ventricles/pathology , L-Lactate Dehydrogenase/drug effects , L-Lactate Dehydrogenase/blood , Malondialdehyde/analysis , Myocardial Infarction/pathology , Nitric Oxide/analysis
4.
Acta cir. bras ; 33(4): 386-395, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-886279

ABSTRACT

Abstract Purpose: To investigate the safety and clinical, hemodynamic and tissue improvement ability in mini pigs undergoing cell and gene therapy for the treatment of acute myocardial infarction. Methods: Thirty-two mini pigs Br1 lineage, 12 months old, undergoing induction of acute myocardial infarction by occlusion of the diagonal branch of the paraconal coronary. They were divided into 4 groups: one control group and 3 treatment groups (cell therapy and gene cell therapy). Echocardiography reviews were performed on three occasions and histopathological analysis was performed after 4 weeks. Analysis of variance (ANOVA), Tukey and Wilcoxon tests, were performed. Results: Association of vascular endothelial growth factor (VEGF) with angiopoietin1 (Ang1) presented satisfactory results in the improvement of ventricular function following ischemic cardiomyopathy in mini pigs when compared to the results of the other treated groups. Conclusion: The therapy with VEGF and the combination of VEGF with Ang1, promoted recovered function of the myocardium, characterized by reduced akinetic area and induction of neovascularization.


Subject(s)
Animals , Genetic Therapy/methods , Ventricular Function/physiology , Angiopoietin-1/therapeutic use , Vascular Endothelial Growth Factor A/therapeutic use , Cell- and Tissue-Based Therapy/methods , Myocardial Infarction/therapy , Swine , Swine, Miniature , Wound Healing , Echocardiography , Reproducibility of Results , Treatment Outcome , Neovascularization, Physiologic , Disease Models, Animal , Hemodynamics/physiology , Myocardial Infarction/physiopathology , Myocardial Infarction/pathology , Necrosis
5.
Arq. bras. cardiol ; 110(3): 278-288, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-888039

ABSTRACT

Abstract Many non-invasive methods, such as imaging tests, have been developed aiming to add a contribution to existing studies in estimating patients' prognosis after myocardial injury. This prognosis is proportional to myocardial viability, which is evaluated in coronary artery disease and left ventricular dysfunction patients only. While myocardial viability represents the likelihood of a dysfunctional muscle (resulting from decreased oxygen supply for coronary artery obstruction), hibernation represents post-interventional functional recovery itself. This article proposes a review of pathophysiological basis of viability, diagnostic methods, prognosis and future perspectives of myocardial viability. An electronic bibliographic search for articles was performed in PubMed, Lilacs, Cochrane and Scielo databases, according to pre-established criteria. The studies showed the ability of many imaging techniques in detecting viable tissues in dysfunctional areas of left ventricle resulting from coronary artery injuries. These techniques can identify patients who may benefit from myocardial revascularization and indicate the most appropriate treatment.


Resumo Diversos métodos não invasivos, como novos exames de imagem, vem sendo aprimorados, a fim de somar esforços com os atuais em estimar o prognóstico de pacientes pós-injúria miocárdica. Este prognóstico é proporcional à viabilidade miocárdica, a qual tem sua avaliação reservada para pacientes portadores de doença arterial coronariana e insuficiência ventricular esquerda. Enquanto a viabilidade miocárdica se mostra como a capacidade de recuperação funcional do músculo com disfunção por redução de oxigênio fornecido por artérias coronárias obstruídas, a hibernação consiste na própria recuperação funcional após intervenções. Este artigo propõe uma revisão sobre as bases fisiopatológicas do processo de viabilidade, métodos diagnósticos disponíveis, prognóstico e perspectivas para o futuro acerca dessa condição. Realizou-se pesquisa de busca bibliográfica informatizada em bases eletrônicas de dados, como PubMed, Lilacs, Cochrane e Scielo, onde foram selecionados os estudos de acordo com critérios pré-determinados. Os estudos demonstram a capacidade de várias técnicas de imagem de identificar tecido viável em regiões disfuncionais do ventrículo esquerdo em decorrência de lesões em artérias coronárias. Estas técnicas podem identificar pacientes com potencial benefício da revascularização miocárdica e orientar o tratamento mais adequado.


Subject(s)
Humans , Tissue Survival/physiology , Myocytes, Cardiac/pathology , Myocardial Infarction/pathology , Myocardial Infarction/diagnostic imaging , Myocardium/pathology , Prognosis , Coronary Artery Disease/physiopathology , Coronary Artery Disease/pathology , Coronary Artery Disease/diagnostic imaging , Magnetic Resonance Imaging/methods , Echocardiography/methods , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Heart/diagnostic imaging , Myocardial Infarction/physiopathology , Myocardial Revascularization
6.
J. appl. oral sci ; 26: e20170199, 2018. tab, graf
Article in English | LILACS, BBO | ID: biblio-893736

ABSTRACT

Abstract The presence of neopterin in gingival crevicular fluid (GCF) is a marker for local and acute immune activation, and the presence of vascular cell adhesion molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular inflammation. Objectives This study aimed to evaluate effects of periodontal treatment on GCF levels of neopterin and VCAM-1 in patients with chronic periodontitis (CP) with acute myocardial infarction (AMI) compared with systemically healthy CP patients. Material and methods Sixty subjects (20 CP patients with AMI, 20 healthy CP patients, and 20 healthy controls) were included. GCF samples were analyzed at baseline and after 3 and 6 months, and the probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing, gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent assay (ELISA). No significant differences were seen between the AMI+CP and CP groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline. Results The number of teeth with 5 mm≤CAL<7 mm and CAL≥7 mm were significantly increased in the AMI+CP group at baseline. There were no significant differences between the AMI+CP and CP for PI, CAL, GCF volumes, and the AMI+CP group had the highest clinical improvement in the number of teeth with 5 mm≤CAL<7 mm at the sixth month. There were significant positive correlations between clinical periodontal inflammation and the presence of neopterin and VCAM-1 in GCF prior to and following periodontal treatment, and between the GCF volume and clinical parameters. Conclusions Data suggest that the total amount and concentration of neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal disease severity in CP patients with AMI. Moreover, the results of our study demonstrate that the past periodontal status is potentially correlated between groups, with similar periodontal disease severity.


Subject(s)
Humans , Male , Female , Adult , Aged , Gingival Crevicular Fluid/chemistry , Vascular Cell Adhesion Molecule-1/analysis , Neopterin/analysis , Chronic Periodontitis/pathology , Chronic Periodontitis/therapy , Myocardial Infarction/pathology , Reference Values , Time Factors , Severity of Illness Index , Enzyme-Linked Immunosorbent Assay , Case-Control Studies , Periodontal Index , Dental Plaque Index , Analysis of Variance , Treatment Outcome , Periodontal Attachment Loss , Statistics, Nonparametric , Risk Assessment/methods , Chronic Periodontitis/complications , Middle Aged , Myocardial Infarction/etiology
7.
Article in English, Portuguese | LILACS | ID: biblio-909208

ABSTRACT

O diabetes mellitus é uma doença epidêmica. Os adultos portadores de diabetes têm taxas de doenças cardiovasculares duas a três vezes maiores do que aquelas observadas em adultos não diabéticos. O reconhecimento de que o diabetes é uma doença heterogênea em relação ao risco cardiovascular foi fundamental para a identificação correta dos indivíduos sob maior risco, os quais necessitam de tratamento farmacológico mais intensivo, e daqueles cujo risco é menor, em que o uso de medidas não farmacológicas isoladamente em uma fase inicial é opcional. Ferramentas para estratificação de risco mais precisas, uso apropriado de métodos de rastreamento de isquemia no paciente assintomático e indicação dos métodos de imagem são brevemente revisados neste capítulo. O tratamento de todos os fatores de risco inclui a moderna abordagem do paciente com diabetes, visando a redução de eventos macro e microvasculares. Descritores: Diabetes mellitus; Doença da artéria coronariana; Infarto do miocárdio; Acidente vascular cerebral.


Diabetes mellitus can be considered an epidemic disease. Adults with diabetes have two to three times higher rates of cardiovascular disease than those observed in non-diabetic adults. The recognition that diabetes is a heterogeneous disease in relation to cardiovascular risk was fundamental for the correct identification of individuals at higher risk, who require more intensive pharmacological intervention, and those at lower risk, where the use of non-pharmacological strategies alone in an initial phase is optional. More precise risk stratification tools, the appropriate use of screening methods for tracking ischemia in the asymptomatic patient, and the indication of imaging tests will be summarized in this review. Treatment based on global risk factor control includes the modern approach for the patient with diabetes, aiming at reducing both macro- and microvascular events.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Coronary Artery Disease/complications , Diabetes Mellitus/epidemiology , Dyslipidemias/epidemiology , Myocardial Infarction/pathology , Risk Factors
8.
Rev. Assoc. Med. Bras. (1992) ; 63(9): 733-735, 2017. graf
Article in English | LILACS | ID: biblio-896404

ABSTRACT

Summary Although myocardial rupture occurs in only 2% to 4% of cases of acute myocardial infarction (AMI), there is a high mortality rate due to acute cardiogenic shock. We present the anatomopathological findings of three cases of myocardial rupture in autopsied hearts in the last 30 years, with a diagnosis of cardiac rupture in acute myocardial infarction. In these 30 years the percentage of AMI with myocardial rupture was 0.2%. Risk factors for post-AMI myocardial rupture include older age, atherosclerosis, diabetes mellitus and systemic arterial hypertension.


Resumo Embora a ruptura do miocárdio ocorra em apenas 2 a 4% dos casos de infarto agudo do miocárdio (IAM), está associada a alta mortalidade, principalmente em decorrência do estado de choque cardiogênico agudo. São apresentados os achados anatomopatológicos de três casos de ruptura do miocárdio de pacientes autopsiados nos últimos 30 anos, com diagnóstico de ruptura cardíaca em decorrência de IAM. Nesse período, a porcentagem de IAM com ruptura do miocárdio foi de 0,2%. Os fatores de risco para ruptura do miocárdio pós-IAM incluem idade avançada, arteriosclerose, diabetes mellitus e hipertensão arterial sistêmica.


Subject(s)
Humans , Male , Female , Aged , Heart Rupture, Post-Infarction/pathology , Autopsy , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/pathology
9.
Acta cir. bras ; 32(5): 376-387, May 2017. tab, graf
Article in English | LILACS | ID: biblio-837712

ABSTRACT

Abstract Purpose: To investigate whether modulating GSK-3β could attenuate myocardial ischemia reperfusion injury (MIRI) induced acute lung injury (ALI) and analyze the underlying mechanism. Methods: Male SD rats were subjected to MIRI with or without myocardial ischemic post-conditioning in the presence or absence of GSK-3β inhibitor. GSK-3β inhibitor was injected peritoneally 10min before MIRI. Lung W/D weight ratio, MPO, PMNs, histopathological changes, TUNEL, Bax, Bcl-2, IL-6, IL-8, IL-10, GSK-3β, and caspase-3 were evaluated in the lung tissues of all rats. Results: After MIRI, lung injury was significantly increased manifested as significant morphological changes and increased leukocytes in the interstitial capillaries, Lung W/D ratio, MPO, and PMN in BALF, which was associated with enhanced inflammation evidenced by increased expressions of IL-6, IL-8 and reduced expression of IL-10. MIRI significantly increased cell apoptosis in the lung as increased levels of apoptotosis, Bax, cleaved caspase-3, and reduced expression of Bcl-2 was observed, which was concomitant with reduced p-GSK-3β. All these changes were reversed/prevented by ischemic post-conditioning, while these beneficial effects of ischemic post-conditioning were abolished by GSK-3β inhibition. Conclusion: Myocardial ischemia reperfusion injury induces acute lung injury by induction of inflammation and cell apoptosis. Ischemic post-conditioning protects the lung from ALI following MIRI by increasing p-GSK-3β.


Subject(s)
Animals , Male , Myocardial Reperfusion Injury/prevention & control , Protective Agents/metabolism , Acute Lung Injury/prevention & control , Ischemic Postconditioning/methods , Glycogen Synthase Kinase 3 beta/metabolism , Random Allocation , Down-Regulation , Interleukins/metabolism , Rats, Sprague-Dawley , Apoptosis/drug effects , Peroxidase/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Protective Agents/pharmacology , In Situ Nick-End Labeling , Models, Animal , Enzyme Activation , bcl-2-Associated X Protein/metabolism , Caspase 3/metabolism , Acute Lung Injury/enzymology , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Glycogen Synthase Kinase 3 beta/pharmacology , Inflammation/metabolism , Myocardial Infarction/pathology , Neutrophils/enzymology
10.
Autops. Case Rep ; 6(4): 15-19, Oct.-Dec. 2016. ilus
Article in English | LILACS | ID: biblio-885174

ABSTRACT

Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis.


Subject(s)
Humans , Female , Child , Myocardial Infarction/pathology , Myocarditis/pathology , Autopsy/methods , Diagnosis, Differential , Fatal Outcome , Heparin/therapeutic use
13.
Acta cir. bras ; 31(5): 338-345, May 2016. tab, graf
Article in English | LILACS | ID: lil-783802

ABSTRACT

ABSTRACT PURPOSE: To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. METHODS: Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. RESULTS: The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. CONCLUSION: Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.


Subject(s)
Animals , Male , Autonomic Nervous System/drug effects , Myocardial Ischemia/physiopathology , Anesthetics, Inhalation/pharmacology , Ischemic Preconditioning, Myocardial/methods , Methyl Ethers/pharmacology , Myocardial Infarction/physiopathology , Pulse , Autonomic Nervous System/physiology , Time Factors , Blood Pressure/drug effects , Blood Pressure/physiology , Echocardiography , Random Allocation , Rats, Wistar , Myocardial Ischemia/etiology , Myocardial Ischemia/diagnostic imaging , Models, Animal , Heart Rate/drug effects , Heart Rate/physiology , Myocardial Infarction/pathology , Myocardial Infarction/prevention & control , Myocardial Infarction/diagnostic imaging
14.
Acta cir. bras ; 31(3): 190-197, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-777097

ABSTRACT

ABSTRACT PURPOSE: To investigate the effects of Borage oil on cardiac remodeling after myocardial infarction (MI). METHODS: Male Wistar rats underwent ligation of the left coronary artery and divided into three groups: MI (control), BO-18 (18 mg/kg of borage oil) and BO-180 (180 mg/kg of borage oil). After seven days, heart was arrested in diastole and processed for histological evaluation of: MI size, LV dilation, myocyte hypertrophy, inflammatory infiltration and fibrosis in MI region and in remote region. The relative weight of the lung was used as a marker of heart failure. The MI size was comparable among groups. RESULTS: Compared to control, BO treated groups showed lower weight of heart and lungs, reduced LV dilation and myocyte hypertrophy. Hemodynamic measurements were comparable. The treatment attenuated the inflammatory infiltration and fibrosis in remote myocardium. CONCLUSION: Borage oil attenuates progression of cardiac remodeling after myocardial infarction and congestive heart failure.


Subject(s)
Animals , Male , Plant Oils/pharmacology , gamma-Linolenic Acid/pharmacology , Ventricular Remodeling/drug effects , Heart Ventricles/pathology , Anti-Inflammatory Agents/pharmacology , Myocardial Infarction/pathology , Organ Size , Fibrosis , Rats, Wistar , Models, Animal , Myocytes, Cardiac/drug effects , Heart Failure/pathology , Lung/pathology
15.
Clinics ; 71(3): 163-168, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-778995

ABSTRACT

OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87). CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which seemed to be related to the presence of PPAR-α.


Subject(s)
Animals , Female , Myocardial Infarction/metabolism , PPAR alpha/metabolism , Physical Conditioning, Animal/physiology , Apoptosis/physiology , Inflammation/metabolism , Models, Animal , Myocardial Infarction/pathology , Myocardial Infarction , NF-kappa B/metabolism , PPAR alpha/analysis , Random Allocation , Rats, Wistar , Time , Tumor Necrosis Factor-alpha/metabolism , Ventricular Function/physiology
16.
Article in English | WPRIM | ID: wpr-110209

ABSTRACT

OBJECTIVE: To assess magnetic resonance imaging (MRI) features of coronary microembolization in a swine model induced by small-sized microemboli, which may cause microinfarcts invisible to the naked eye. MATERIALS AND METHODS: Eleven pigs underwent intracoronary injection of small-sized microspheres (42 microm) and catheter coronary angiography was obtained before and after microembolization. Cardiac MRI and measurement of cardiac troponin T (cTnT) were performed at baseline, 6 hours, and 1 week after microembolization. Postmortem evaluation was performed after completion of the imaging studies. RESULTS: Coronary angiography pre- and post-microembolization revealed normal epicardial coronary arteries. Systolic wall thickening of the microembolized regions decreased significantly from 42.6 +/- 2.0% at baseline to 20.3 +/- 2.3% at 6 hours and 31.5 +/- 2.1% at 1 week after coronary microembolization (p < 0.001 for both). First-pass perfusion defect was visualized at 6 hours but the extent was largely decreased at 1 week. Delayed contrast enhancement MRI (DE-MRI) demonstrated hyperenhancement within the target area at 6 hours but not at 1 week. The microinfarcts on gross specimen stained with nitrobluetetrazolium chloride were invisible to the naked eye and only detectable microscopically. Increased cTnT was observed at 6 hours and 1 week after microembolization. CONCLUSION: Coronary microembolization induced by a certain load of small-sized microemboli may result in microinfarcts invisible to the naked eye with normal epicardial coronary arteries. MRI features of myocardial impairment secondary to such microembolization include the decline in left ventricular function and myocardial perfusion at cine and first-pass perfusion imaging, and transient hyperenhancement at DE-MRI.


Subject(s)
Animals , Coronary Angiography/methods , Coronary Vessels/pathology , Disease Models, Animal , Embolism/pathology , Female , Heart/diagnostic imaging , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/methods , Microspheres , Myocardial Contraction/physiology , Myocardial Infarction/pathology , Myocardium/pathology , Nitroblue Tetrazolium , Staining and Labeling , Swine , Troponin T/blood , Ventricular Function, Left
17.
Cad. saúde pública ; 31(3): 496-506, 03/2015. tab
Article in English | LILACS | ID: lil-744841

ABSTRACT

This study analyzes the available evidence on the adequacy of economic evaluation for decision-making on the incorporation or exclusion of technologies for rare diseases. The authors conducted a structured literature review in MEDLINE via PubMed, CRD, LILACS, SciELO, and Google Scholar (gray literature). Economic evaluation studies had their origins in Welfare Economics, in which individuals maximize their utilities based on allocative efficiency. There is no widely accepted criterion in the literature to weigh the expected utilities, in the sense of assigning more weight to individuals with greater health needs. Thus, economic evaluation studies do not usually weigh utilities asymmetrically (that is, everyone is treated equally, which in Brazil is also a Constitutional principle). Healthcare systems have ratified the use of economic evaluation as the main tool to assist decision-making. However, this approach does not rule out the use of other methodologies to complement cost-effectiveness studies, such as Person Trade-Off and Rule of Rescue.


El objetivo fue sistematizar las evidencias disponibles sobre la pertinencia de utilizar la evaluación económica para la incorporación/exclusión de tecnología en enfermedades raras. Se realizó una revisión sistemática de la literatura en MEDLINE vía PubMed, CRD, LILACS, SciELO y Google Académico (literatura gris). Los estudios de evaluación económica se originan de la Economía del Bienestar, en la que los individuos maximizan sus utilidades, basándose en la eficiencia de asignación. No existe un criterio ampliamente aceptado para examinar las utilidades, a fin de dar más peso a los individuos con mayores necesidades. Generalmente, los estudios no equilibran asimétricamente las utilidades, todas son consideradas iguales, lo que en Brasil es también un principio constitucional. Los sistemas de salud han ratificado el uso de la evaluación económica como la principal herramienta para ayudar en la toma de decisiones. Sin embargo, este abordaje no excluye el uso de otras metodologías complementarias a los estudios de coste-efectividad, como la técnica de compensación personal o la regla del rescate.


O objetivo deste estudo foi analisar as evidências disponíveis sobre a adequação do uso de avaliação econômica sobre incorporação/exclusão de tecnologias para doenças raras. Foi realizada uma revisão estruturada da literatura, nas bases MEDLINE, via PubMed, CRD, LILACS, SciELO e Google Acadêmico (literatura cinzenta). Os estudos de avaliação econômica têm origem na Economia do Bem-Estar, na qual os indivíduos maximizam suas utilidades, fundamentando-se na eficiência alocativa. Não há um critério amplamente aceito para ponderar as utilidades esperadas, no sentido de dar mais peso aos indivíduos com maiores necessidades em saúde. Geralmente não se ponderam assimetricamente as utilidades; todas são tratadas de forma igualitária, que, no caso brasileiro, também é um princípio constitucional. Os sistemas de saúde têm ratificado o uso de avaliação econômica como principal instrumento para auxiliar na tomada de decisão. No entanto, essa postura não exclui o uso de outras metodologias complementares aos estudos de custo-efetividade, como Person Trade-Off e regra de resgate.


Subject(s)
Animals , Humans , Mice , Atherosclerosis/enzymology , Atherosclerosis/pathology , Foam Cells/enzymology , Matrix Metalloproteinases/metabolism , Aortic Rupture/etiology , Aortic Rupture/prevention & control , Atherosclerosis/complications , Atherosclerosis/immunology , Foam Cells/pathology , Gene Expression Regulation, Enzymologic , Lipid Metabolism , Models, Immunological , Matrix Metalloproteinases/genetics , Myocardial Infarction/complications , Myocardial Infarction/enzymology , Myocardial Infarction/immunology , Myocardial Infarction/pathology , Myocytes, Smooth Muscle/pathology , Tissue Inhibitor of Metalloproteinases/immunology , Tissue Inhibitor of Metalloproteinases/metabolism
18.
Article in English | WPRIM | ID: wpr-61310

ABSTRACT

It is uncertain that atorvastatin pretreatment can reduce myocardial damage in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the effects of atorvastatin pretreatment on infarct size measured by contrast-enhanced magnetic resonance imaging (CE-MRI) in STEMI patients. Patients undergoing primary PCI for STEMI within 12 hr after symptom onset were randomized to an atorvastatin group (n = 30, 80 mg before PCI and for 5 days after PCI) or a control group (n = 37, 10 mg daily after PCI). The primary end point was infarct size evaluated as the volume of delayed hyperenhancement by CE-MRI within 14 days after the index event. The median infarct size was 19% (IQR 11.1%-31.4%) in the atorvastatin group vs. 16.3% (7.2%-27.2%) in the control group (P = 0.27). The myocardial salvage index (37.1% [26.9%-58.7%] vs. 46.9% [39.9-52.4], P = 0.46) and area of microvascular obstruction (1.1% [0%-2.0%] vs. 0.7% [0%-1.8%], P = 0.37) did not differ significantly between the groups. Frequency of the hemorrhagic and transmural infarctions was not significantly different in the 2 groups. Pretreatment with a high-dose atorvastatin followed by further treatment for 5 days in STEMI patients undergoing primary PCI failed to reduce the extent of myocardial damage or improve myocardial salvage.


Subject(s)
Adult , Aged , Atorvastatin/pharmacology , Electrocardiography , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Image Enhancement , Magnetic Resonance Imaging , Male , Middle Aged , Myocardial Infarction/pathology , Myocardium/pathology , Percutaneous Coronary Intervention , Prospective Studies
20.
Arq. bras. cardiol ; 103(2): 124-130, 08/2014. tab, graf
Article in English | LILACS | ID: lil-720810

ABSTRACT

Background: Gender can influence post-infarction cardiac remodeling. Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. Results: MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Conclusions: Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function. .


Fundamento: O gênero pode ser decisivo no remodelamento cardíaco após infarto do miocárdio. Objetivo: Avaliar diferenças de gênero associadas ao remodelamento do ventrículo esquerdo (VE) após infarto do miocárdio (IM) e associadas à modulação de quinases acopladas à integrina (integrin-linked kinases-ILK). Métodos: Ratos Wistar machos e fêmeas foram divididos em 3 grupos: grupo sham, grupo com IM de extensão moderada (tamanho: 20-39% da área do VE); grupo com IM de grande extensão (tamanho: ≥ 40% da área do VE). O IM foi produzido por oclusão coronária e as análises ecocardiográficas foram obtidas após 6 semanas para avaliar a extensão do IM, bem como a morfologia e função do VE. RT-PCR em tempo real e Western blott foram realizados para quantificar a ILK no miocárdio. Resultados: A extensão do IM foi semelhante entre os gêneros. O IM resultou em disfunção sistólica e aumento do tamanho do VE no final da diástole e da sístole em função do tamanho da área necrótica para ambos os sexos. Ratos fêmeas com IM de grande extensão apresentaram dilatação diastólica e sistólica inferior a de ratos machos, mas a disfunção do VE foi semelhante em ambos os sexos. Os níveis gênicos e proteicos de ILK aumentaram em ratos fêmeas com infartos de extensão moderada e grande, mas apenas ratos machos com infartos de grande extensão apresentaram níveis alterados de mRNA do ILK. Uma correlação linear negativa foi observada entre as dimensões do VE e a expressão de ILK em ratos fêmeas com IM de grande extensão. Conclusões: A expressão de ILK pós-IM variou de maneira gênero-especifica, e os níveis mais elevados de ILK observados em ...


Subject(s)
Animals , Female , Male , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Protein-Serine-Threonine Kinases/metabolism , Sex Factors , Ventricular Remodeling/physiology , Blotting, Western , Diastole/physiology , Echocardiography , Myocardial Infarction , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reference Values , Systole/physiology , Time Factors , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left
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