Troponin Levels Research Articles

Cardiovascular Complications in Respiratory Viral Infections with a Focus on COVID-19

Patients with respiratory viral infections have altered immune responses, which may predispose them to cardiovascular complications. In the face of the pandemic of a new kind of severe acute respiratory syndrome (SARS), coronavirus disease 2019 (COVID-19), there is a resurgence of interest in the early diagnosis, prevention, and treatment of patients who are at risk. COVID-19 often manifests as viral pneumonia, although extrapulmonary manifestations are also common. Acute cardiac damage associated with elevated highsensitivity troponin levels crucially contributes to mortality in severe COVID-19. The present review clinically compares cardiovascular complications between COVID-19 and other respiratory infections caused by singlestranded RNA viruses, namely influenza, SARS, and Middle East respiratory syndrome (MERS). Estimating the death rate from RVIs has been a subject of intense research, but the mortality from cardiovascular complications in these infections is less understood and calls for further research.

ST-Segment Alterations in the Electrocardiogram of Acute Pulmonary Thromboembolism: A Rabbit Model

In this study, we investigated the mechanism underlying electrocardiogram (ECG) alterations in a rabbit model of acute pulmonary thromboembolism (PTE). Twelve healthy adult New Zealand white rabbits were used, with eight in the experimental group (PTE group) and four in the control group. After developing the rabbit model of acute PTE, ECG and coronary angiography were performed. HE staining was conducted on the right and left ventricular tissues, and polymerase chain reaction (PCR) was used to determine brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), and Troponin I (TNI) mRNA expression in the myocardium. There were considerable changes in the ST segment of the ECG in the PTE group. Coronary angiography revealed the absence of spasm, stenosis, and occlusion. In the plasma of the PTE group, the levels of D-dimer, BNP, TNF-α, and TNI were significantly elevated, and these changes were statistically significant (P<0.05). PCR analysis of ventricular myocardial tissue indicated significantly higher levels of BNP, TNF-α, and TNI mRNA in the PTE group than in the control group. These differences were statistically significant (P<0.05). The ST-T variations on the ECG of rabbits with acute PTE correlate strongly with the temporary changes in right heart volume caused by acute PTE.

Cardiac Evaluation of Children Presenting with Trauma

Background: Trauma is a critical public health issue, particularly impacting the young and caus-ing significant financial and moral losses. Approximately one-third of trauma-related hospitaliza-tions and 20-25% of trauma-related deaths are caused by serious chest injuries. We aimed to determine the prognostic value of changing pediatric global troponin levels in the emergency department after trauma. Materials and Methods: Patients who applied to the emergency department with complaints of trauma between January 1, 2015 and January 31, 2022 were evaluated. Records of pediatric patients between the ages of 0 and 18 were reviewed. The cause and severity of the trauma, electrocardiography and echocardiography results, and laboratory data (biochemical, hemogram, C-reactive protein, pro-BNP, CK-MB, troponin, etc.) of the patients were evaluated. This study is an observational and retrospective. Results: Falling from height was the most prevalent cause of injury, accounting for 43% of cases. Chest trauma was observed in 55 patients (56%). All patients with chest trauma exhibited ele-vated troponin levels. Troponin levels were found to be significantly higher in patients with chest trauma (p=0.011). Conclusions: Our findings highlighted the prognostic importance of cardiac troponins, especially in pediatric patients presenting with trauma.

Assessment of Troponin Levels as a Biomarker of Myocardial Injury in Patients with Fatal Covid-19 for the Period 2020 to 2022: A Literature Review

Background: COVID-19 initially described at the end of 2019. COVID-19 is caused by an uncommon ‎coronavirus infection. Since then, it has been spreading rapidly and has caused a global pandemic, infecting more than 29 million people and causing more than ‎‎900,000 deaths as of September 15, 2020. In most cases this disease mainly affects the respiratory ‎system and can cause a syndrome called acute respiratory distress, leading to acute ‎respiratory failure. However, COVID-19 causes other systemic ‎indications, such as myocardial injury, coagulopathy, and cytokine storm. Myocardial injury patients were determined by elevated troponin levels by large number of COVID-19 patients, ranging from ''7.2% to 36%''. COVID-19 patients may experience myocardial injury due to other complications such as ‎arrhythmias, heart failure, or even sudden cardiac arrest, as well, COVID-19 is a complex disease that can cause severe respiratory ‎failure. Understanding these complications is crucial for ‎managing the disease ‎and developing effective treatment. Aim: This review research aims to assess the roles of troponin in COVID-19 patients at a higher risk of ‎myocardial injury, as well as shed light on the most significant research articles conducted in this ‎field of regard area between 2020 and 2022. Methods and Materials: This review outlined the latest scientific research for the period from 2020 to ‎‎2022 ‎associated with the involvement of cardiac injury in the population of COVID-19 ‎‎patients by focusing on the use of troponin levels as a vital ‎indication. Additionally, it is starting from ‎encountered patients with COVID-19, as well as it‎‏ is ‏‎related to the increased risk of ‎death data and it had a crucial role in the identification of COVID-19 with a high risk of hypoxia in the blood. At that point, it was going through the evidence regarding COVID-19 and ‎cardiovascular biomarkers, such as troponin articles recognized using the electronic ‎search, as performed via PubMed, Embase, and Google Scholar Database through a ‎comprehensive search conducted by combining key terms for instance; “biomarkers”, ’’myocarditis”, “COVID-19”, “troponin”. English-language articles were screened for ‎relevance and a full review of publications for the important studies was conducted, ‎including additional publications identified from individual article ‎reference lists. Conclusion: Cardiac troponin (cTn) is the most reliable test for detecting heart disease, particularly myocardial injury. Elevated levels of troponin (both cTnI and cTnT) are a critical risk factor for severe myocardial injury and hospitalizations, especially for COVID-19 patients who face a higher risk of adverse events. Therefore, measuring cTn levels is critical to monitor the progression of heart disease and effectively manage patients'

The impact of spinal anesthesia on cardiac function in euvolemic vascular surgery patients: insights from echocardiography and biomarkers.

Existing evidence of the effect of spinal anesthesia (SA) on cardiac systolic function is scarce and inconclusive. This study aimed to evaluate the effects induced by a single injection of SA for elective vascular surgery on left (LV) and right (RV) ventricular systolic performance using transthoracic echocardiography (TTE). A prospective study. Single-center study, university hospital. Adult patients undergoing elective vascular surgery with SA. During patients' evaluations fluid administration was targeted using arterial waveform monitoring. All patients underwent TTE studies before and after SA induction for the assessment of indices reflective of LV and RV systolic function. Blood samples were drawn to measure troponin and brain natriuretic peptide (BNP) levels. A total of 62 patients (88.7% males, 71.00 ± 9.42 years) were included in the study. The primary outcome was the difference before and after SA in LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE). In total population, LVEF significantly increased after SA 53.07% [16.51]vs 53.86% [13.28]; p < 0.001). End-systolic volume (ESV, 69.50 [51.50] vs. 65.00 [29.50] ml; p < 0.001) decreased while stroke volume (SV) insignificantly increased (70.51 ± 16.70 vs. 73.00 ± 18.76ml; p = 0.131) during SA. TAPSE remained unchanged (2.23 [0.56] vs. 2.25 [0.69] mm; p = 0.558). In patients with impaired compared to those with preserved LV systolic function, the changes evidenced in LVEF (7.49 ± 4.15 vs. 0.59 ± 2.79; p < 0.001), ESV (-18.13 ± 18.20 vs-1.53 ± 9.09; p < 0.001) and SV (8.71 ± 11.96 vs-1.43 ± 11.89; p = 0.002) were greater. This study provides evidence that SA in patients undergoing elective vascular surgery improved LV systolic function, while changes in RV systolic function are minimal.

Physical Exercise Increases Cardiac Troponin (cTn) Levels as a Marker of Myocardial Infarction: A Systematic Review

Objectives. This study aimed to analyze an indication of physical exercise on the increase of cardiac troponin (cTn) levels as a marker of myocardial infarction from the physiological perspective. Materials and methods. A search of journal databases including MEDLINE-Pubmed, Web of Science, Scopus, and Science Direct was used in this systematic review study. The inclusion criteria were papers that addressed cardiac troponin (cTn), physical activity, and myocardial infarction, and were published within the last five years. Using the databases Science Direct, Pubmed, and Web of Science, 83 recognized publications were found. For this systematic review, finally ten publications that fulfilled the requirements for inclusion were chosen and examined. This study evaluated standard operating procedures using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results. This systematic review reports that physical exercise has been found to increase cardiac troponin (cTn) levels as a marker of myocardial infarction, but this increase is triggered by the body’s physiological response during exercise and is not considered as a pathological response. Conclusions. According to the findings of the study, physical exercise has been proven to elevate the risk of heart muscle damage by triggering an increase in cardiac troponin (cTn). However, this feature occurs in a physiological state and represents an exercise adaptation process. An analysis of the relevant articles reveals that this increase in cardiac troponin (cTn) has not been shown to have a negative influence on developing cardiovascular disease.

Endurance Exercise Does Not Exacerbate Cardiac Inflammation in BALB/c Mice Following mRNA COVID-19 Vaccination.

The mechanism underlying myopericarditis associated with mRNA COVID-19 vaccination, including increased susceptibility in young males, remains poorly understood. This study aims to explore the hypothesis that engaging in physical exercise at the time of mRNA COVID-19 vaccination may promote a cardiac inflammatory response, leading to the development of myopericarditis. Male BALB/c mice underwent treadmill running or remained sedentary for five weeks. Subsequently, two doses of the Pfizer/BioNTech vaccine or vehicle were administered with a 14-day interval, while the exercise regimen continued. The animals were euthanized days after the second vaccination. Vaccination was followed by body weight loss, increased hepatic inflammation, and an antigen-specific T cell response. Small foci of fibrovascular inflammation and focal cell loss were observed in the right ventricle, irrespective of vaccination and/or exercise. Vaccination did not elevate cardiac troponin levels. Cardiac tissue from the vaccinated mice showed upregulated mRNA expression of the genes IFNγ and IL-1β, but not IL-6 or TNFα. This pro-inflammatory signature in the heart was not exacerbated by endurance exercise. Ex vivo vascular reactivity remained unaffected by vaccination. Our data provide evidence for the cardiac safety of mRNA COVID-19 vaccination. The role of exercise in the development of pro-inflammatory cardiac changes post mRNA vaccination could not be established.

Use of downstream stress imaging tests for risk stratification of patients presenting to the emergency department with chest pain and low HEART score

BackgroundPatients with low HEART (History, Electrocardiogram, Age, Risk factors, and Troponin level) risk scores who are discharged from the emergency department (ED) may present clinical challenges and diagnostic dilemmas. The...

Biochemical Risk Factors of Atherosclerosis in Patients with Severe and Non-severe COVID-19

Background: COVID-19 may trigger the progression of atherosclerosis, potentially leading to its clinical manifestation. Among the serum biomarkers related to atherosclerotic disease, it seems helpful to evaluate biochemical factors such as CD147, ACE2, and ACE in patients with COVID-19. Methods: In this case-control study, serum samples from 90 patients were analyzed. The cohort included 30 patients hospitalized in the intensive care unit with COVID-19, 30 patients hospitalized in the ward with COVID-19, and 30 healthy individuals from Ayatollah Kashani Hospital (Tehran, Iran). These patients were admitted between December 10, 2022, and March 10, 2023. The concentrations of cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the activity levels of angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), troponin, CPK, CPK-MB, and CD147 were determined and analyzed among the three groups. Results: There was no significant difference in age between the patients (55.40 ± 10.34 years) and the control group (58.34 ± 11.71 years). SARS-CoV2 viral RNA was detected in the pharyngeal swab samples of the COVID-19 patients. The levels of CD-147 (2528.43 ± 12.43 vs. 2176.7 ± 9.87 vs. 1346.3 ± 14.23), ACE (83 ± 3.05 vs. 97 ± 1.55 vs. 30.1 ± 2.32), troponin (0.972 ± 0.25 vs. 0.784 ± 0.21 vs. 0.021 ± 0.68), and cholesterol (199.73 ± 2.43 vs. 175.87 ± 5.21 vs. 144.97 ± 8.74) were significantly higher in severe cases compared to non-severe cases (P &lt; 0.05). ACE (AUC = 0.894) and CD147 (AUC = 0.821) had the highest sensitivity and specificity among the studied factors, respectively. Patients with normal levels of ACE and CPK-MB had a 0.16 times lower and 4.37 times greater chance of experiencing severe disease, respectively. Three strong correlations were found among the studied parameters: CD147 with ACE2 (r = 0.721) and cholesterol with triglyceride (r = 0.602) (P &lt; 0.05). Conclusions: Examining ACE and CD147 can help determine a person's susceptibility to atherosclerosis. These two factors have greater sensitivity and specificity and could be used as potential markers for monitoring disease progression.

Assessing risk factors and time to viral clearance on maintenance hemodialysis patients with COVID-19: a retrospective study

BackgroundPatients on maintenance hemodialysis (MHD) have been disproportionately affected by COVID-19. Identifying factors associated with disease severity and viral clearance times can inform better clinical management for this high-risk group.MethodsWe retrospectively analyzed clinical and hematological data from 85 COVID-19 positive MHD patients. Disease severity was classified as non-severe (mild/moderate) or severe (severe/critical). Logistic regression was used to evaluate factors associated with disease severity. The time to viral clearance was assessed and correlated with clinical variables.ResultsCardiovascular disease (OR=11.19, 95% CI 2.35–53.38), neutrophilia (OR=1.24, 95% CI 1.01–1.53), and elevated inflammatory markers (procalcitonin and white blood cell count) were independent predictors of severe COVID-19. A prognostic model incorporating these factors showed good discrimination for severity risk (AUC=0.835). The median time to viral clearance was 19 days. Delayed clearance was associated with higher levels of C-reactive protein, troponin, and N-terminal pro-B-type natriuretic peptide.ConclusionsWe identified key prognostic factors for COVID-19 severity and characterized the time to viral clearance in MHD patients. These findings can aid in risk stratification and optimize management for this vulnerable population. Further research through multicenter collaborative studies is warranted to validate these results.

High sensitivity troponins and mortality in the population with metabolic dysfunction-associated steatotic liver disease

Given the global high prevalence of MASLD and its poor CVD prognosis, it is essential to perform risk stratification for MASLD patients. The specific impact of High Sensitivity Troponins (hs-cTn ) on mortality in MASLD patients remains unexplored. The NHANES databases from 1999 to 2004, which include data on high-sensitivity cardiac troponin (hs-cTn) levels and comorbidities, were linked with the most recent mortality dataset. Myocardial injury was determined using the 99th upper reference limits (URL) for hs-cTn. Our study included 3460 MASLD patients. The mean follow-up duration was 192 months, during which 1074 (23%) MASLD participants died from all-cause mortality, and 363 (7.3%) died from CVD mortality. Our findings indicate that MASLD patients with elevated levels of hs-cTnT (> 99th URL) exhibit increased risks of all-cause mortality [adjusted hazard ratio (aHR) = 1.93] and CVD mortality (aHR = 2.4). Similar results were observed for hs-cTnI, where the aHRs for all-cause mortality and CVD mortality were 2.03 and 2.97, respectively. Furthermore, we identified a nonlinear dose-response relationship between hs-cTn levels and the risk of mortality (P for nonlinearity < 0.001). Our findings suggest that hs-cTn can predict mortality risk in MASLD, aiding clinicians in risk-stratifying this population. Therefore, we recommend considering hs-cTn detection in individuals with MASLD to effectively assess their future mortality risk.

Adverse effects of metamizole on heart, lung, liver, kidney, and stomach in rats

BackgroundMetamizole is banned in some countries because of its toxicity, although it is widely used in some European countries. In addition, there is limited information on its safety profile, and it is still debated whether it is toxic to the heart, lungs, liver, kidneys, and stomach.AimsOur study investigated the effects of metamizole on the heart, lung, liver, kidney, and stomach tissues of rats.MethodsEighteen rats were divided into three groups, wassix healthy (HG), 500 mg/kg metamizole (MT-500), and 1000 mg/kg metamizole (MT-1000). Metamizole was administered orally twice daily for 14 days. Meanwhile, the HG group received pure water orally. Biochemical, histopathologic, and macroscopic examinations were performed on blood samples and tissues.ResultsMalondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in the lung and gastric tissues of MT-500 and MT-1000 groups were almost the same as those of the HG (p > 0.05). However, MDA levels in the heart and liver tissues of MT-500 and MT-1000 groups were higher (p < 0.05) compared to the HG, while tGSH levels and SOD, and CAT activities were lower (p < 0.05). MDA levels of MT-500 and MT-1000 groups in the kidney tissue increased the most (p < 0.001), and tGSH levels and SOD and CAT activities decreased the most (p < 0.001) compared to HG. Metamizole did not cause oxidative damage in the lung and gastric tissue. While metamizole did not change troponin levels, it significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels compared to HG. Histopathologically, mild damage was detected in heart tissue, moderate damage in liver tissue, and severe damage in renal tissue. However, no histopathologic damage was found in any groups’ lung and gastric tissues.ConclusionMetamizole should be used under strict control in patients with cardiac and liver diseases and it would be more appropriate not to use it in patients with renal disease.

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study

PurposeThe aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Materials and MethodsBlood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. ResultsHS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. ConclusionSignificant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

Factors influencing the prognosis of patients with cardiogenic shock treated with extracorporeal membrane oxygenation: A protocol for systematic review and meta-analysis.

Cardiogenic shock is a clinical syndrome caused by primary heart disease that results in decreased cardiac output and insufficient systemic perfusion. A study was conducted to determine what factors affect survival in patients with cardiogenic shock treated with extracorporeal membrane oxygenation (ECMO). A systematic search was conducted across various databases, including CKNI, VIP, Wan Fang, CBM, Embase, PubMed, Cochrane Library, and Web of Science databases, to gather factors linked to the prognosis of patients with cardiogenic shock who underwent ECMO treatment. The search period for each database was set to conclude on April 30, 2024. The findings suggest that, in comparison to the death group, the lactic acid levels of the survival group after treatment were significantly lower (95% confidence interval [CI]: -0.79, -0.58). In addition, the creatinine levels of the survival group after treatment were also significantly lower than those of the death group (95% CI: -0.39, -0.14). Furthermore, the troponin levels in the survival group after treatment were lower than those in the death group (95% CI: -0.32, 0.04), and the total bilirubin levels in the survival group after treatment were also lower than those in the death group (95% CI: -0.62, -0.23). According to the study, total bilirubin, creatinine, and lactic acid levels were lower in the survival group than in the death group when ECMO was used to treat cardiogenic patients, suggesting a better prognosis for patients with cardiogenic shock. Therefore, total bilirubin, creatinine, and lactic acid could be influential factors in the prognosis of survival in patients with cardiogenic shock.

Assessing subaortic right ventricle function after atrial switch repair through myocardial work analysis

BackgroundThe Mustard and Senning operations for dextro-transposition of the great arteries (D-TGA) establish a biventricular physiology with a subaortic right ventricle (sRV). While prolonged QRS has been associated with worse prognosis in these patients, current echocardiographic tools fall short in adequately assessing the (mal)performance and function decline of the sRV during follow-up. The present study is the first to characterize Myocardial Work (MW) indices of the sRV in D-TGA patients after Mustard/Senning repair. Methods and resultsAll adult D-TGA patients at follow-up in the University Hospital of Leuven between 2018 and 2022 were screened for inclusion. We retrospectively collected the most recent electrocardiogram parameters, 2D echocardiographic images and serum biomarkers’ values. Offline calculations of MW indices were performed. We established correlations between all variables and categorized patients into QRS<120 ms and QRS≥120 ms for further analysis. A total of 51 D-TGA patients were included (13 Mustard, 33 male, 39 ± 6 years). QRS duration increased with age and was correlated with sRV dimensions and serum levels of troponins (R = 0.42, p < 0.01) and NT-proBNP (R = 0.31, p = 0.03). However, no significant correlation was found between QRS duration and intraventricular desynchrony or conventional functional echocardiographic parameters. QRS prolongation was associated with a deterioration in septal, but not lateral, MW parameters. Patients with QRS≥120 ms had significantly larger ventricles and higher levels of troponins and NT-proBNP. ConclusionQRS prolongation after Mustard/Senning repair is linked to ventricular dilatation and worse performance, particularly affecting the septal wall. Global and regional MW analysis may be useful to assess the subclinical deterioration of sRV function.

Ginseng Radix et Rhizoma enhanced the effect of metoprolol in chronic heart failure by inhibiting autophagy in male C57BL/6J mice.

Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol is widely used in patients with HF. However, there is no report on the combined effects of GS and metoprolol in patients with HF. This study investigated the combined effects of GS and metoprolol in male C57BL/6J mice with HF and the underlying mechanisms. We utilized a mouse myocardial HF model to measure the serum levels of creatine kinase (CK) and creatine kinase-MB form (CK-MB) using an automated biochemical analyzer. Lactate dehydrogenase (LDH) and cardiac troponin (cTnT) levels were determined using enzyme-linked immunosorbent assays. Autophagy of myocardial cells was evaluated using transmission electron microscopy, and changes in signal pathway proteins related to autophagy were analyzed by Western blotting. GS combined with metoprolol improved heart function, reduced heart damage, and decreased serum levels of CK, CK-MB, LDH, and cTnT. The combination of GS and metoprolol decreased autophagy in myocardial cells by reducing the levels of autophagy-related proteins (LC3, p62, Beclin1, and Atg5) and increasing the ratios of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. GS enhanced the anti-heart failure effect of metoprolol. Its mechanism of action might be related to the inhibition of autophagy mediated by the activation of the PI3K/Akt/mTOR pathway.

Association Between High-Sensitivity Troponin (hs-cTnT) and Diagnosis of Myocarditis in Previously Healthy Pediatric Patients.

Cardiac troponin is commonly used to screen for cardiac diagnoses in pediatric patients, as it is only released by myocardial tissue. There is limited data regarding high-sensitivity troponin T in pediatric populations and its clinical interpretation. We sought to determine how high-sensitivity troponin values are associated with myocarditis diagnosis. High sensitivity troponin levels were reviewed for pediatric patients at our center from February 2022 to February 2023. Basic demographic and presenting data (including age, gender, body mass index), and diagnoses (cardiac diagnosis, including myocarditis, vs non-cardiac) were compared for patients with elevated initial troponin levels (≥ 12ng/L) vs. those with non-elevated values. Of the 308 patients included, 91 (29.5%) had elevated hs-cTnT and 45 (14.6%) had a cardiac diagnosis, of whom 8 (2.5%) were ultimately diagnosed with acute myocarditis. There was no meaningful difference in demographic characteristics between the elevated and non-elevated hs-cTnT groups. For patients with diagnosis of myocarditis (n = 8), median peak levels were 506.5ng/L (182.0 to 1184.0) versus 6.0ng/L (< 6.0 to 13.5) for those with all other diagnoses (n = 300) (p < 0.001). A high sensitivity troponin cut-off value of 90ng/dL was established for diagnosis of myocarditis, providing high sensitivity (100%) and specificity of (95%).

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Persicae Semen ameliorated acute myocardial ischemia in rats by regulating the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism

Persicae Semen is an edible Chinese herbal medicine that ameliorates myocardial ischemia. However, its pharmacodynamic properties and mechanisms of action remain unclear. This study aimed to investigate the ameliorative effect of Persicae Semen extract (PS) on acute myocardial ischemia (AMI) in rats and explore its mechanism of action. After the PS administration to rats, 12 compounds were identified in the plasma. PS can significantly improve cardiac function, regulate creatine kinase (CK), creatine kinase MB (CK-MB), cardiac troponin (cTn I), α-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels in the serum, and ameliorate the pathological injury of AMI in rats. Metabolomics and network pharmacology of components absorbed in to plasma showed that PS may regulate the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism, then ameliorate myocardial ischemic injury. This study found that PS significantly improved cardiac function in rats with AMI, through the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism.

Abstract We073: CLEC4E Signaling in Myocardial Ischemia-Reperfusion Injury

Background: The innate immune receptor CLEC4E (C-type lectin domain family 4 member E) in cardiac resident cells and circulating leukocytes contributes to ischemic myocardial damage and adverse LV remodeling following ischemia reperfusion injury (I/R). Mice with loss of CLEC4E gene function show reduced cardiac injury and better LV remodeling but the mechanisms of this cardioprotection remain unknown. Aims: We investigated whether Clec4e gene function in cardiac resident cells vs infiltrating immune cells mediates cardioprotection during myocardial ischemia-reperfusion injury. Methods: We generated chimeric mice by IV infusion of 5 x 10 6 bone marrow cells originating from C57Bl6/J CLEC4E -/- and C57Bl6/J wild-type (WT) donor mice in 8w-old lethally irradiated (9.5 Gy) WT (n=36) and CLEC4E -/- (n=50) receptor mice, respectively. After 4 w, mice were subjected to ischemia reperfusion injury (I/R) by 60 min LAD occlusion. Troponin levels (TnI) were measured at 90 min post I/R and 7T-magnetic resonance imaging with late gadolinium enhancement (LGE) for infarct size evaluation was performed at 24 h and 28 d post I/R. Mice were euthanized at 28 days for immunohistochemistry and analysis of BM chimerism. Results: Immunohistochemistry for CLEC4E expression on bone marrow smears confirmed successful BM chimerism. At 24h post I/R, TnI levels and LGE-assessed infarct size on MRI were not significantly different between groups (42.1 vs 48.4 ng/ml, and 25.2% vs 31.5% of LVmass in CLEC4E -/- &amp; WT BM versus in WT &amp; CLEC4E -/- BM, respectively) suggesting similar myocardial damage . After 28 d, LV end-diastolic volumes (43µL vs 55µL), and end-systolic volumes (13µL vs 25µL) were significantly smaller in CLEC4E -/- &amp; WT BM than in WT &amp; CLEC4E -/- BM mice (P&lt;0.05 for both), resulting in better preserved global LV function (LVEF 62% vs 47%, P&lt;0.05) . Infarct size, semiquantitatively assessed using planimetry on Sirius red stains, was smaller in CLEC4E -/- &amp; WT BM than in WT &amp; CLEC4E -/- BM (6.9% vs 19.8%, P&lt;0.01). Conclusion: CLEC4E gene deletion in cardiac resident cells, but not in infiltrating hematopoietic immune cells is associated with better functional and structural remodelling after myocardial I/R. Inhibition of CLEC4E signaling via blocking antibodies or small molecule inhibitors in cardiac myocytes might be a promising cardioprotective strategy.