Sodium tanshinone IIA sulfonate improves adverse ventricular remodeling post MI by reducing myocardial necrosis, modulating inflammation and promoting angiogenesis

Background and Objective: Myocardial infarction (MI) leads to pathological cardiac remodeling and heart failure. Sodium tanshinone IIA sulfonate (STS) shows therapeutic values. The present study aimed to explore the potential role of STS in ventricular remodeling post-MI Methods: Mice were randomly divided into sham, MI + normal saline (NS) and MI + STS (20.8 mg/kg/day intraperitoneally) groups. MI was established following left anterior descending artery ligation. Cardiac function was evaluated using echocardiography. Scar size and myocardial fibrosis-associated markers were detected using Masson’s trichrome staining and western blot analysis (WB). Necrosis and inflammation were assessed using H&E staining, lactate dehydrogenase (LDH) detection, ELISA, immunohistochemical staining, and WB. Furthermore, angiogenesis markers and associated proteins were detected using immunohistochemical staining and WB. Results: Mice treated with STS exhibited significant improvements in cardiac function, smaller scar size, and low expression levels of α-smooth muscle actin and collagen I and III at 28 days following surgery, compared with the NS-treated group. Moreover, treatment with STS reduced eosinophil necrosis, the infiltration of inflammatory cells, plasma levels of LDH, high mobility group protein B1, interleukin-1β and tumor necrosis factor-α, and protein expression of these cytokines at 3 days. Macrophage infiltration was also decreased in the STS group in the early phase. Additionally, CD31+ vascular density, protein levels of hypoxia-inducible factor-1α, and vascular endothelial growth factor were elevated in the STS-treated mice at 28 days. Conclusion: STS improved pathological remodeling post-MI, and the associated therapeutic effects may result from a decrease in myocardial necrosis, modulation of inflammation, and an increase in angiogenesis.

Biomarkers of Inflammation and Oxidative stress in the Prediction and Management of Acute Coronary Syndrome

The assessment of patients presenting with chest pain or symptoms indicative of cardiac ischemia remains a diagnostic challenge. Many types of research have focused on the search for ideal biological markers for the rapid detection of cardiac cell injuries. Markers of inflammation and oxidative stress are the way forward. At present, the biomarker most widely used for diagnosing acute coronary syndrome is cardiac troponin though it has some limitations. Apart from cardiac troponin, several other biomarkers, especially inflammation and oxidative stress markers in acute coronary syndrome, have been investigated. However, most of them still require validation in further studies. As markers of inflammation and oxidative stress address a particular aspect of the pathophysiology of acute coronary syndrome, these biomarkers may provide unique information to the managing clinician separate from that of markers of myocyte necrosis. Serum markers of inflammation and oxidative stress appear before cardiac necrosis markers and are valuable targets for early and timely diagnosis of an acute cardiac event. Using these markers in combination with biomarkers of plaque formation, unstable plaque development, plaque rupture, thrombosis, and myocardial necrosis (multimarker approach) could increase their diagnostic and prognostic value.

Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.

Cooling of cultured water can resist heart failure caused by collagen deposition and necrosis of cardiac fibers under chronic heat stress in sturgeon

Background Chronic heat stress (CHS) may threaten the survival of cultivated and wild sturgeon by jeopardizing heart function. Methods Therefore, we established a heart damage model for the Siberian sturgeon (Acipenser baerii) using varying degrees of CHS (24°C and 28°C) to explore its effect on the heart structure and function, and their mutual relationship. Results Our research showed that CHS caused systemic heart failure in A. baerii, clinically manifested as severely irregular ventricles, increased myocardial fibrotic in the interstitium of cardiomyocytes, and myocardial necrosis. Echocardiographic imaging of A. baerii revealed an accelerated heart rate, incomplete ventricular contraction, decreased cardiac output, and significantly reduced pumping efficiency under CHS. Generally, the contractility of the heart decreased and the afterload increased under CHS, which is typical of high-resistance and low-output heart failure. However, cooling of cultured water (20°C) can offset the adverse effects of partial or total CHS on tissue structure and function. Conclusion Our results systematically characterized the relationship between the effects of CHS on the heart structure and heart function in sturgeon. This work provides a preliminary reference for future summer breeding pond management and protection of sturgeon.

Remote Ischemic Conditioning in Ischemic Stroke and Myocardial Infarction: Similarities and Differences

Acute myocardial infarction and ischemic stroke are leading causes of morbidity and mortality worldwide. Although reperfusion therapies have greatly improved the outcomes of patients with these conditions, many patients die or are severely disabled despite complete reperfusion. It is therefore important to identify interventions that can prevent progression to ischemic necrosis and limit ischemia-reperfusion injury. A possible strategy is ischemic conditioning, which consists of inducing ischemia – either in the ischemic organ or in another body site [i.e., remote ischemic conditioning (RIC), e.g., by inflating a cuff around the patient's arm or leg]. The effects of ischemic conditioning have been studied, alone or in combination with revascularization techniques. Based on the timing (before, during, or after ischemia), RIC is classified as pre-, per-/peri-, or post-conditioning, respectively. In this review, we first highlight some pathophysiological and clinical similarities and differences between cardiac and cerebral ischemia. We report evidence that RIC reduces circulating biomarkers of myocardial necrosis, infarct size, and edema, although this effect appears not to translate into a better prognosis. We then review cutting-edge applications of RIC for the treatment of ischemic stroke. We also highlight that, although RIC is a safe procedure that can easily be implemented in hospital and pre-hospital settings, its efficacy in patients with ischemic stroke remains to be proven. We then discuss possible methodological issues of previous studies. We finish by highlighting some perspectives for future research, aimed at increasing the efficacy of ischemic conditioning for improving tissue protection and clinical outcomes, and stratifying myocardial infarction and brain ischemia patients to enhance treatment feasibility.

Study the Value of Interleukin-6 As Diagnostic and Predictive marker of Cardiac Events in St Segment Elevation Myocardial Infarction

Background Owing to major changes in the biomarkers available for diagnosis, criteria for acute myocardial infarction have been revised. The current international consensus definition states that the term acute myocardial infarction (AMI) should be used when there is evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. The present guidelines pertain to patients presenting with ischemic symptoms and persistent ST-segment elevation on the electrocardiogram (ECG). Most of these patients will show a typical rise in biomarkers of myocardial necrosis and progress to Q wave myocardial infarction. Separate guidelines have recently been developed by another task force of the ESC (European Society of Cardiology) for patients presenting with ischemic symptoms but without persistent ST segment elevation and for patients undergoing myocardial revascularization in general. Aim of the work The aims of this work are: To assess the diagnostic value of interleukin-6 compared to troponin I in ST segment elevation myocardial infarction. To assess the predictive value of elevated interleukin-6 in ST segment elevation myocardial infarction. Patients This prospective study was included sixty adult patients of both sexes meeting the American Heart Association (AHA) recommendations for diagnosis of ST segment elevation myocardial infarction from those attending the Critical Care Units, Critical Care Medicine Department, Faculty of Medicine, Ain Shams University to be included in the current study. Inclusion Criteria :Patients were fulfilled the criteria of diagnosis of acute coronary syndrome (ACS) and diagnosed as ST segment elevation MI according to American Heart Association (AHA) criteria which include patient ranging between 30 to 70 years and presented with active chest pain. Exclusion Criteria Patients were excluded from the study if they have: (1) Recent myocardial infarction in the last three months. (2) Recent cardiological intervention in the last three months. (3) Recent ischemic cerebrovascular stroke in the last three months. (4) Non ST segment elevation myocardial infarction and unstable angina according to electrocardiographic changes, cardiac markers and clinical condition of the patients. (5) Acute infectious diseases that leads to elevation of troponin I and interleukin-6. (6) Active immunological diseases. (7) Renal impairment. Methods The following data were obtained from each patient: Personal data: name, age, sex, occupation and special habits e.g. smoking. History of present illness regarding to clinical condition: onset, nature, duration, course, progression, characteristic site and radiating areas of the chest pain, relieving and aggravating factors, associated symptoms (as diaphoresis, nausea, vomiting, dyspnea and palpitation) and medication received and their effects. Medical history of diabetes mellitus (DM), hypertension (HTN), and history of ischemic heart disease (IHD). Family history of IHD, DM and HTN. Conclusion From this current study we revealed that: STEMI patients have increased level of interleukin-6 compared to those normal persons. Interleukin-6 may be a potentially useful marker for diagnosis of STEMI. Interleukin-6 may be helpful prognostic value for future cardiac mortality in STEMI patients. The level of interleukin-6 is not affected by the extent of myocardial damage and necrosis. Interleukin-6 is an inflammatory cytokine. Recommendations From this study we recommend the use of interleukin-6 level as good diagnostic marker for diagnosis of ST segment elevation myocardial infarction, Also this study recommend the use of interleukin-6 as good prognostic inflammatory marker in future adverse cardiac events and mortality occur after myocardial infarction STEMI type. Study limitations The results are interpreted in consideration of the small population of patients and short term follow up.

Association between the osmotic fragility of erythrocytes and the course of acute myocardial infarction

Aim. To investigate the relationship between the osmotic fragility of erythrocytes and the course of acute myocardial infarction (MI).Methods. An analysis of the osmotic fragility of erythrocytes was conducted using beta-blocker-based osmotic fragility test in sixty-two patients within the first 6 hours after onset of MI symptoms.Results. The results revealed that the patients with increased erythrocyte osmotic fragility experienced more complications after acute MI, such as left ventricular failure and cardiac arrhythmias (ventricular extrasystoles and ventricular tachycardia) (p = 0.026). Moreover, these patients exhibited greater myocardial injury - the concentration of biomarkers of myocardial necrosis, such as creatine phosphokinase, creatine phosphokinase MB and Troponin I was increased - p = 0.009, p = 0.032 and p = 0.001, respectively. In addition to that, the patients with high osmotic fragility had a larger number of hypokinetic and akinetic segments, high impaired myocardial contractility index, and low ejection fraction. The impaired myocardial contractility index was significantly higher in patients with increased erythrocyte osmotic fragility (1.5 (1.22; 1.75) vs 1.12 (1.0; 1.56), U = 157.5, p = 0.032).Conclusion. Increased erythrocyte osmotic fragility in patients was associated with greater myocardial injury, manifesting through the higher concentration of biomarkers of myocardial necrosis in blood, as well as higher number of hypokinetic segments.

Mitochondrial Oxidation of the Cytoplasmic Reducing Equivalents at the Onset of Oxidant Stress in the Isoproterenol-Induced Rat Myocardial Infarction

We have developed and characterized a model of isoproterenol (ISO)-induced myocardial necrosis, identifying three stages of cardiac damage: a pre-infarction (0–12 h), infarction (24 h), and post-infarction period (48–96 h). Using this model, we have previously found alterations in calcium homeostasis and their relationship with oxidant stress in mitochondria, which showed deficient oxygen consumption and coupled ATP synthesis. Therefore, the present study was aimed at assessing the mitochondrial ability to transport and oxidize cytoplasmic reducing equivalents (NADH), correlating the kinetic parameters of the malate-aspartate shuttle, oxidant stress, and mitochondrial functionality. Our results showed only discreet effects during the cardiotoxic ISO action on the endogenous malate-aspartate shuttle activity, suggesting that endogenous mitochondrial NADH oxidation capacity (Nohl dehydrogenase) was not affected by the cellular stress. On the contrary, the reconstituted system showed significant enhancement in maximal capacity of the malate-aspartate shuttle activity only at later times (post-infarction period), probably as a compensatory part of cardiomyocytes’ response to the metabolic and functional consequences of the infarcted tissue. Therefore, these findings support the notion that heart damage associated with myocardial infarction suffers a set of sequential biochemical and metabolic modifications within cardiomyocytes, where mitochondrial activity, controlling the redox state, could play a relevant role.

Extremely high troponin levels induced by septic shock: a case report

Background Troponin levels can be elevated in various diseases other than acute myocardial infarction, including sepsis. In diseases without myocardial necrosis, the elevated troponin levels are relatively low and normalize quickly. Case presentation A 61-year-old Japanese man with impaired consciousness was transported to our hospital. He was diagnosed as having pneumonia and septic shock. His condition was severe, but his clinical course was good. However, his troponin level remained extremely high during admission; on the second day, it was higher than the measurable range. We consulted a cardiologist and performed echocardiography and myocardial perfusion scintigraphy but found no new ischemic changes. Conclusion In septic shock, troponin levels can be extremely high, which can persist even after recovery, as in very large myocardial infarctions.

Gut Lactobacillus Level Is a Predictive Marker for Coronary Atherosclerotic Lesions Progress and Prognosis in Patients With Acute Coronary Syndrome

BackgroundGut microbiota dysbiosis can contribute to the progression of atherosclerosis. We investigated the association of the gut microbiota and the severity of coronary artery lesions and prognosis of patients with ACS.MethodsIn this case-control study, 402 ACS patients and 100 controls were enrolled from June 2017 to December 2018. The number of bacterial species was determined by real-time PCR. A SYNTAX score was calculated for all ACS patients based on their coronary angiography results.ResultsCompared with the healthy controls, the gut microbial levels in Escherichia coli, Streptococcus, and Enterobacteriaceae were significantly increased in ACS patients, while the Lactobacillus level was significantly decreased. Lactobacillus level was as an independent predictor of disease severity on the coronary angiography [high vs. low SYNTAX score: adjusted odds ratio (aOR) = 0.024, 95% confidence interval (CI): 0.004–0.155] and myocardial necrosis [high vs. low cardiac troponin T (cTNT): aOR = 0.317, 95% CI: 0.099–0.914]. Subsequently, a higher Lactobacillus level was associated with a lower risk of an all-cause death [adjusted hazard ratio (aHR) = 0.239; 95% CI: 0.093–0.617] and major adverse cardiac events (MACE) in ACS patients (aHR = 0.208; 95% CI: 0.081–0.531). After stratifying by the type of ACS, a higher Lactobacillus level was significantly associated with the decreased risks of high SYNTAX score, all-cause death, and MACE in the STEMI subgroup but not in the NSTEMI and UAP subgroups.ConclusionsLower Lactobacillus levels may indicate a higher risk of a more severe coronary atherosclerotic lesions and myocardial necrosis and worse prognosis for patients with ACS, particularly in the STEMI subgroup.