Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction.

Studies were carried out on the metabolism of lipid peroxides and antioxidative enzymes during diabetes and diabetes superimposed with myocardial infarction. Diabetes was induced using alloxan and myocardial infarction was induced by isoproterenol. In the case of diabetic animals there was a decrease in the levels of lipid peroxides in the heart while in the case of diabetes associated with myocardial infarction it was slightly elevated. The activity of superoxide dismutase and catalase showed a decrease in both the groups. Glutathione showed a fall in the case of diabetes and diabetes associated with myocardial infarction while taurine in heart and ceruloplasmin in the serum was elevated. Histopathological changes in the heart tissue showed some focal changes in the case of both diabetes and diabetes associated with myocardial infarction, but the degree of necrosis was much less than in the case of myocardial infarction.     

Effect of adaptation to short-term stress exposure on the fibrillation threshold and ectopic activity of the heart in experimental myocardial infarct

Preliminary adaptation to short-term stress was shown to prevent the decrease in the heart fibrillation threshold and an increase in ectopic activity which is usually observed in experimental myocardial infarction. This protective effect involves an enhanced activity of the antioxidant system. Therefore, a synthetic antioxidant ionol was applied to prevent disturbances of the heart electrical stability in infarction. It was established that ionol completely prevents the decrease in the electrical threshold and the increase in ectopic activity of the heart in experimental infarction. Thus, it can be concluded that ionol possesses an antiarrhythmic effect.     

The dose-dependent effect of 3,5-dicarbomethoxyphenylbiguanide on activity of the glutathione antioxidant system in heart and blood serum of rats with experimental myocardial infarction

Administration of a synthetic compound with predicted anti-ischemic and cardioprotective activity, 3,5-dicarbomethoxyphenylbiguanide (3,5-DCMPBG) to rats with experimental myocardial infarction led to a decrease in the lipid peroxidation level, glutathione peroxidase activity, the level of reduced glutathione, activity of NADP-isocitrate dehydrogenase in the heart and blood serum, and activity of glucoso-6-phosphate dehydrogenase in heart in comparison with their levels in untreated animals with myocardial infarction. This may be attributed to a decrease of free radical processes and reduction of antioxidant system loading induced by the protective effect of the administered compound. At the same time the increase glutathione reductase activity observed under these conditions in the heart and blood serum is probably associated with specific influence of 3,5-DCMPBG on this enzyme.     

Changes in the concentration of catecholamines in the organs of animals with experimental myocardial infarcts under the influence of malaben]

The content of adrenaline and noradrenaline in the tissues of the heart, adrenal glands, spleen and brain of rats was studied in experimental myocardial infarction. A significant decrease in the catecholamine levels was revealed in the tissues. Malaben promoted normalization of the catecholamine tissue content in myocardial infarction. It is suggested that the said effect of malaben is due to its antihistaminic properties.     

Prevention of stress-related disorders in the contractile function of non-ischemic areas of the heart during myocardial infarction using gamma-hydroxybutyric acid

Contractile function of an isolated right auricle of the rat was studied one day after producing an experimental infarction of the left ventricle. It was disclosed that in this non-ischemized heart area there developed marked decrease in myocardial extensibility and depression of contractile function manifesting in an approximately two-fold lowering of the developing tension. These stress-induced disturbances prevented by administering GABA prior to myocardial infarction production. It is assumed that the action of GABA is accounted for by its capability to protect non-ischemized areas of the myocardium against harmful stress action.     

血清Trx1、FGL2与急性心肌梗死后心力衰竭患者预后的关系

摘要 目的：探讨血清硫氧还蛋白1（Trx1）、纤维蛋白原样蛋白2（FGL2）与急性心肌梗死后心力衰竭患者预后的关系。方法：选择2019年10月至2020年5月我院收治的158例急性心肌梗死后心力衰竭患者作为观察组,并根据心功能Killip分级分为Ⅱ级组54例、Ⅲ级组57例、Ⅳ级组47例。另选择同期我院收治的102例急性心肌梗死患者作为对照组。入院后采用酶联免疫吸附法（ELISA）检测所有患者血清Trx1、FGL2水平;观察组患者出院后随访2年,并根据是否出现主要不良心血管事件（MACE）将患者分为预后不良组和预后良好组。采用多因素Logistic回归分析影响急性心肌梗死后心力衰竭患者预后的相关因素,采用受试者工作特征（ROC）曲线评估血清Trx1、FGL2对急性心肌梗死后心力衰竭患者预后的预测价值。结果：观察组血清FGL2水平明显高于对照组,血清Trx1水平明显低于对照组（P<0.05）;心功能Killip分级Ⅳ级组患者血清Trx1水平明显低于Ⅱ级组、Ⅲ级组（P<0.05）,血清FGL2水平明显高于Ⅱ级组、Ⅲ级组（P<0.05）。预后不良组患者血清Trx1、LVEF均明显低于预后良好组,而年龄、血清FGL2及血尿酸、血肌酐、N末端B型利钠肽原（NT-proBNP）均明显高于预后良好组（P<0.05）,两组心功能Killip分级比例比较差异有统计学意义（P<0.05）。多因素Logistic回归分析显示,年龄（较高）、心功能Killip分级为Ⅳ级、Trx1下降、FGL2升高均是影响急性心肌梗死后心力衰竭患者预后的危险因素（P<0.05）。ROC曲线结果显示,血清Trx1、FGL2预测急性心肌梗死后心力衰竭患者预后的曲线下面积分别为0.807、0.811,两者联合检测预测急性心肌梗死后心力衰竭患者预后的曲线下面积为0.889。结论：急性心肌梗死后心力衰竭患者血清中Trx1水平降低,FGL2水平升高,且血清Trx1、FGL2水平与患者心功能分级及预后密切相关,可作为评估急性心肌梗死后心力衰竭患者预后的辅助性指标。     

Decline in ischaemic heart disease in Iceland and change in risk factor levels.

OBJECTIVE--To monitor trends in mortality and morbidity due to ischaemic heart disease and compare these with observed levels of risk factors from population surveys. DESIGN--Analysis of trends in death rates from ischaemic heart disease in Iceland compared with expected rates computed from population surveys. Risk factor levels together with beta factors obtained from Cox''s regression analysis were used to compute expected death rates. Trends in morbidity due to acute myocardial infarction were assessed and secular trends in dietary consumption compared with trends in cholesterol concentrations. SETTING--Reykjavik, Iceland (total population 250,000; over half the population live in Reykjavik). SUBJECTS--12,814 randomly selected residents in the Reykjavik area aged 45-64 (6623 men, 6191 women; 72% and 80% of those invited). MAIN OUTCOME MEASURES--Age adjusted rates of myocardial infarction and deaths from ischaemic heart disease. Expected risk from risk factor levels (smoking, total serum cholesterol concentration, systolic blood pressure) at each unique survey visit. RESULTS--Mortality from ischaemic heart disease has decreased by 17-18% since 1970. During 1981-6 the myocardial infarction attack rate in men under 75 decreased by 23%. A decrease occurred in the level of all three major risk factors after 1968. The fall in the serum cholesterol concentration coincided with a reduction in consumption of dairy fat and margarine. The calculated reduction in risk for the age group 45-64 was about 35%, which was closely similar to the observed decrease in mortality due to ischaemic heart disease in that age group. CONCLUSION--The reduction in mortality from ischaemic heart disease was substantially due to a decreased incidence of myocardial infarction and could be attributed largely to the reduction in risk factors.     

Effect of abana an ayurvedic formulation,on lipid peroxidation in experimental myocardial infarction in rats

The present study was conducted to elucidate the antioxidant role of an ayurvedic formulation Abana in isoproterenol induced myocardial infarction in rats. In myocardial necrosis induced by isoproterenol, a significant increase in serum iron content with a significant decrease in plasma iron binding capacity, ceruloplasmin activity and glutathione level were observed. There was also a significant increase in lipid peroxides levels on isoproterenol administration. Activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase, glutathione reductase were decreased significantly in heart with isoproterenol-induced myocardial necrosis. Abana, produced a marked reversal of these metabolic changes related to myocardial infarction induced by isoproterenol. In conclusion ayurvedic formulation Abana exerts its effect by modulating lipid peroxidation and enhancing antioxidant and detoxifying enzyme systems.     

Alterations in the heart lysosomal stability in isoproterenol induced myocardial infarction in rats

The alterations in the heart lysosomal stability following isoproterenol induced myocardial infarction were studied in albino rats. The rate of release of beta-glucuronidase at various time intervals at 37 degrees C from lysosome rich fraction was taken as a measure of lysosomal stability. As compared to the control day one, three and five samples exhibited a significant increase in beta-glucuronidase activity at all the time intervals. The subcellular distribution of beta-glucuronidase was also studied and the soluble and total activities exhibited an increase at peak infarction stage and returned to normal during the recovery. The decrease in the lysosomal stability might be attributed to the increased beta-glucuronidase activity observed following myocardial infarction.     

Clinical observations and echocardiographic features of mural thrombi in the left ventricle during myocardial infarction]

The incidence and changes in the mural thrombi in left ventricle in ECHO-2D in the acute myocardial infarction as well as relationship between clinical parameters and echocardiographic indices of the left cardiac ventricle contractability asynergy and dynamics of changes in mural thrombi have been investigated. The studies included 137 consecutive patients (98 males and 39 females) treated for the acute myocardial infarction. Patients' age ranged from 35 to 87 years (mean 62 years). Infarction of the anterior and/or lateral wall was diagnosed in 67 patients, and infarction of the inferior and/or posterior wall in 70 patients. Mural thrombi were diagnosed in 42 (31%) patients. Eighteen thrombi (43%) were liquefied during hospitalization. Comparative analysis of patients in whom mural thrombi underwent liquefaction in the hospital and a group of patients with myocardial infarction and persisting mural thrombi showed that return of left ventricle movements with subsequent contractability facilitate liquefaction of mural thrombi. Higher mortality rate in the group of patients with myocardial infarction with mural thrombi is due to extension of the infarction accompanied by marked asynergy of left ventricular contractions which does not decrease in sequential examinations, and increasing congestive heart failure.     

Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study.

OBJECTIVE--To examine the hypothesis that a J curve relation between blood pressure and death from coronary heart disease is confined to high risk subjects with myocardial infarction. DESIGN--Cohort longitudinal epidemiological study with biennial examinations since 1950. SETTING--Framingham, Massachusetts, USA. SUBJECTS--5209 subjects in the Framingham study cohort followed up by a person examination approach. MAIN OUTCOME MEASURES--Coronary heart disease deaths and non-cardiovascular disease deaths in men and women with or without myocardial infarction relative to blood pressure. RESULTS--Among subjects without myocardial infarction non-cardiovascular disease deaths were twice to three times as common as coronary heart disease deaths. Furthermore, there was no significant relation between non-cardiovascular disease death and diastolic or systolic blood pressure. Also coronary heart disease deaths were linearly related to diastolic and systolic blood pressures. Among high risk patients (that is, people with myocardial infarction but free of congestive heart failure) death from coronary heart disease was more common than non-cardiovascular disease death. There was a significant U shaped relation between coronary heart disease death and diastolic blood pressure. Although there was an apparent U shaped relation between coronary heart disease death and systolic blood pressure, it did not attain statistical significance when controlling for age and change in systolic blood pressure from the pre-myocardial infarction level. None of the above conclusions changed when adjustments were made for risk factors such as serum cholesterol concentration, antihypertensive treatment, and left ventricular function. The U shaped relation between diastolic blood pressure and high risk subjects existed for both those given antihypertensive treatment and those not. CONCLUSIONS--These data suggest that an age and sex independent U curve relation exists for diastolic blood pressure and coronary heart disease deaths in patients with myocardial infarction but not for low risk subjects without myocardial infarction. The relation seems to be independent of left ventricular function and antihypertensive treatment.     

Computational modeling of acute myocardial infarction

Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size.     

Diabetes mellitus and cardiac function

Cardiovascular complications are the most common causes of morbidity and mortality in diabetic patients. Coronary atherosclerosis is enhanced in diabetics, whereas myocardial infarction represents 20% of deaths of diabetic subjects. Furthermore, re-infarction and heart failure are more common in the diabetics. Diabetic cardiomyopathy is characterized by an early diastolic dysfunction and a later systolic one, with intracellular retention of calcium and sodium and loss of potassium. In addition, diabetes mellitus accelerates the development of left ventricular hypertrophy in hypertensive patients and increases cardiovascular mortality and morbidity. Treating the cardiovascular problems in diabetics must be undertaken with caution. Special consideration must be given with respect to the ionic and metabolic changes associated with diabetes. For example, although ACE inhibitors and calcium channel blockers are suitable agents, potassium channel openers cause myocardial preconditioning and decrease the infarct size in animal models, but they inhibit the insulin release after glucose administration in healthy subjects. Furthermore, potassium channel blockers abolish myocardial preconditioning and increase infarct size in animal models, but they protect the heart from the fatal arrhytmias induced by ischemia and reperfusion which may be important in diabetes. For example, diabetic peripheral neuropathy usually presents with silent ischemia and infarction. Mechanistically, parasympathetic cardiac nerve dysfunction, expressed as increased resting heart rate and decreased respiratory variation in heart rate, is more frequent than the sympathetic cardiac nerve dysfunction expressed as a decrease in the heart rate rise during standing.     

急性心肌梗死患者肠道优势菌群分析

目的探讨急性心肌梗死患者肠道优势菌群的改变及其与疾病严重程度的关系。方法共筛选急性心肌梗死患者71名及正常健康体检者33名,急性心肌梗死患者根据是否心衰分为急性心肌梗死组36名和急性心肌梗死伴泵衰竭组35名,所有入选者收集大便及血清标本,分别采用qPCR及化学发光仪测定肠道优势菌群改变和血清脑钠肽前体及肌钙蛋白水平。结果急性心肌梗死患者肠道优势菌群显著改变,肠道肠杆菌以及肠球菌细菌数量较对照组显著增加,均与脑钠肽前体、肌钙蛋白、Killip分级显著正相关,而双歧杆菌、乳酸杆菌等细菌数量显著降低,与脑钠肽前体、肌钙蛋白、Killip分级显著负相关。结论急性心肌梗死患者呈现典型的肠道菌群紊乱,且与患者疾病严重程度相关。     

Protective effects of combination of quercetin and α-tocopherol on mitochondrial dysfunction and myocardial infarct size in isoproterenol-treated myocardial infarcted rats: biochemical, transmission electron microscopic, and macroscopic enzyme mapping evidences

Mitochondrial dysfunction plays an important role in the pathology of myocardial infarction. We evaluated the combined protective effects of quercetin and α-tocopherol on mitochondrial damage and myocardial infarct size in isoproterenol-induced myocardia- infarcted rats. Rats were pretreated with quercetin (10 mg/kg) alone, α-tocopherol (10 mg/kg) alone, and combination of quercetin (10 mg/kg) and α-tocopherol (10 mg/kg) orally using an intragastric tube daily for 14 days. After pretreatment, rats were induced myocardial infarction by isoproterenol (100 mg/kg) at an interval of 24 h for 2 days. Isoproterenol treatment caused significant increase in mitochondrial lipid peroxides with significant decrease in mitochondrial antioxidants. Significant decrease in the activities of isocitrate, succinate, malate, and α-ketoglutarate and NADH dehydrogenases and cytochrome-c-oxidase, significant increase in calcium, and significant decrease in adenosine triphosphate were observed in mitochondria of myocardial infarcted rats. Combined pretreatment with quercetin and α-tocopherol normalized all the biochemical parameters and preserved the integrity of heart tissue and restored normal mitochondrial function in myocardial-infarcted rats. Transmission electron microscopic findings on heart mitochondria and macroscopic enzyme mapping assay on the size of myocardial infarct also correlated with these biochemical parameters. The present study showed that combined pretreatment was highly effective than single pretreatment.     

Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction

Semax, a member of ACTH-derived peptides family, was used in treatment of ischemic stroke in patients. It decreased neurological deficiency and reduced NO hyperproduction in the rat brain caused by acute cerebral hypoperfusion. We suggest that semax is also capable of protecting the rat heart from ischemic damage 28 days after myocardial infarction (MI) induced by left descendent coronary artery occlusion. Semax (150 microg/kg) was given i. p. in the operating day twice: 15 min and 2 hours after coronary occlusion, and once a day for the following 6 days. In 28 days after infarction, the MI group developed cardiac hypertrophy, cell growth was caused mainly by the increase of contractile filaments not supported by the appropriate mitochondrial growth that indicated an impaired energy supply of the cells. Moreover, cardiac hypertrophy was accompanied by decreased mean arterial blood pressure and cardiac contractile function and increased left ventricular end-diastolic pressure. Pharmacological change of cardiac afterload revealed that, in 28 days after MI, the rat heart was not able to change its contractile performance in response to either increase or decrease of systemic blood pressure, and as a result could not maintain its diastolic pressure. All these changes obviously reflect development of heart failure. Semax did not affect cardiac work but partially prevented end-diastolic pressure growth in left ventricle as well as ameliorated cardiomyocyte hypertrophy and disproportionate growth of contractile and mitochondrial apparatus, thus exerting beneficial effect on the left ventricular remodeling and heart failure development late after myocardial infarction.     

Elimination of disorders of the electrical stability of the heart in experimental myocardial infarct and postinfarct cardiosclerosis under the influence of a benzodiazepine receptor agonist

It was shown on Wistar male rats that agonist of benzodiazepine receptors phenazepam considerably suppressed the heart ectopic activity and eliminated disturbances of the heart electric stability in acute myocardial infarction and postinfarction cardiosclerosis. The drug prevented to a considerable extent the death rate of animals within the first day following the ligation of coronary artery and the fall of arterial pressure in animals with the acute myocardial infarction. Possible mechanism of the benzodiazepine agonist effect is under discussion.     

Cardiac arrhythmias in myocardial infarction as an extension of lesions to the myocardium and the state of circulatory efficiency

The study involved 55 patients with the acute myocardial infarction aged between 34 and 69 years (mean 53 years) in whom the relation of cardiac arrhythmias incidence to the extension of myocardial involvement and circulatory efficiency was assessed. All patients were examined clinically, a 24-hour ECG with Holter technique (in the first day, 21st day and 6th months after myocardial infarction) and echocardiographic (Echo-2D) tests were registered. Echocardiography was performed during hospital phase and 6 months after myocardial infarction. Cardiac arrhythmias were evaluated with classification into classes described by Lown. Close relation of serious cardiac arrhythmias with extension of myocardial involvement was noted especially in the acute phase of myocardial infarction. High risk arrhythmias--class IVA, IVB and V were noted in nearly 100% of patients in this phase with cardiac aneurysm, extensive akinesis of apex and anterior wall of the heart. Mean value of the ejection fraction was 31% in this group. Incidence of cardiac arrhythmias did not exceed 40%, ejection fraction was 56% in the group of patients with limited lesions to the heart, e.g. akinesis of the lower wall. Incidence of late cardiac arrhythmias (6 months) did not differ significantly in particular groups of patients. The value of ejection fraction remained, however, on the same level as in the hospital phase of the myocardial infarction.     

Relation between expression of TNF alpha, iNOS, VEGF mRNA and development of heart failure after experimental myocardial infarction in rats.

An injury to the heart due to myocardial infarction (MI) may progress to heart failure. Among factors, whose interactions promote remodeling of ischemic myocardium, the increased expression of tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS) and Vascular Endothelial Growth Factor (VEGF) was found. However, little is known about the temporal and spatial relation between expression of iNOS, cytokine TNFalpha, and growth factor VEGF during pathological process of development of heart failure after the myocardial infarction. Male Sprague-Dawley rats were used for experimental myocardial infarction. The procedure was performed by anterolateral thoracotomy and snearing LAD with the metal clip. The hemodynamic measurements were done with the Langendorff preparation converted into a working heart system. The hemodynamic parameters were recorded at day 6, 11, 28, 40 and the myocardium for gene expression was collected at day 1, 4, 11, 28, 40. Control group was sham operated rats. The VEGF, TNFalpha, iNOS, and GAPDH genes were detected by RT-PCR assay from samples taken at border zone of myocardial infarction. Expression of isoform VEGF120 was found at day 1 and 4 after MI, whereas isoforms VEGF164 and VEGF188 along with expression of TNFalpha and iNOS was found at day 1, 4, 11, 28, 40. No expression of examined genes was detected in the myocardium of control rats. The expression of studied factors was parallel with development of heart failure after myocardial infarction assessed by hemodynamic measurements. These findings confirm the postulated involvement of TNFalpha, iNOS and growth factor VEGF in the remodeling of the myocardium and development of heart failure after experimental myocardial infarction.