Markers Of Myocardial Injury Research Articles

Sclareol attenuates angiotensin II-induced cardiac remodeling and inflammation via inhibiting MAPK signaling.

Chronic inflammation plays an important role in hypertensive heart failure. Suppressing angiotensin II (Ang II)-induced cardiac inflammation may contribute to the treatment of hypertension-associated heart failure. Sclareol, a natural product initially isolated from the leaves and flowers of Salvia sclarea, possesses antiinflammatory and immune-regulation activity in various systems. However, its effect on Ang II-induced cardiac remodeling remains unknown. In this study, we have explored the potential effects of sclareol on Ang II-induced heart failure. In vivo experiments were conducted in mice with Ang II-pump infusion for 28 days. Sclareol administration at 5mg·kg-1 ·d-1 significantly reduced the expression of myocardial injury markers. Sclareol also exerts protective effects against Ang II-induced cardiac dysfunction in mice which is associated with alleviated cardiac inflammation and fibrosis. Transcriptome analysis revealed that inhibition of the Ang II-activated mitogen-activated protein kinase (MAPK) pathway contributed to the protective effect of sclareol. Sclareol inhibits Ang II-activated MAPKs pathway to reduce inflammatory response in mouse hearts and cultured cardiomyocytes. Blockage of MAPKs in cardiomyocytes abolished the antiinflammatory effects of sclareol. In conclusion, we show that sclareol protects hearts against Ang II-induced injuries through inhibiting MAPK-mediated inflammation, indicating the potential use of sclareol in the prevention of hypertensive heart failure.

Evidence construction of baicalin for treating myocardial ischemia diseases: A preclinical meta-analysis

BackgroundBaicalin, a flavonoid glycoside isolated from Scutellaria baicalensis Georgi, has shown potential pharmacological effects on myocardial ischemia diseases. Nevertheless, systematic preclinical studies on baicalin in the treatment of ischemic diseases are scarce. PurposeTo assess the efficacy and potential mechanisms of baicalin in myocardial ischemia (RI), myocardial ischemia-reperfusion (IR) injury and myocardial infarction (MI) animal models for future clinical research. MethodsPreclinical studies published prior to August 27th, 2022 were retrieved from PubMed, Embase, Web of Science and Cochrane Library. CAMARADES list was used to evaluate the quality of included researches. Meta-analyses of cardiac pathology and function parameters, myocardial injury markers and other indicators were performed by STATA 15.0 software. Potential mechanisms are categorized and summarized. Dose-response interval analyses were used to analyze the dose-response relationship between baicalin and myocardial ischemia disease. ResultsFourteen studies and 222 animals were included in the analysis. The results showed that compared with the control group, baicalin could reduce myocardial infarction size associated with cardiac pathological condition and the corresponding cardiac pathological index containing CK-MB, CK and cTnT. Additionally, heart function indicators including LVSP, LVFS, LVEF, -dp/dt max, dp/dt max were increased by baicalin. As for subgroup analyses, baicalin also demonstrated certain effect on CK-MB and LVSP by administration method or stage. Furthermore, it displayed obvious effect on myocardial ischemia diseases when the dose is maintained at 100-150 mg/kg based on dosage analyses. ConclusionBased on the relevant literature retrieved, this is the first meta-analysis on baicalin in treating myocardial ischemia diseases. Notably, we linked the dynamic development of the disease and discussed it pertinently, from RI, IR injury to MI. Baicalin exhibits positive effects on myocardial ischemia diseases (especially when the dose is 100-150 mg/kg), which is achieved by regulating key pathological indicators and various signaling pathways.

Functional components of Chinese rice wine can ameliorate diabetic cardiomyopathy through the modulation of autophagy, apoptosis, gut microbiota, and metabolites.

BackgroundDietary polyphenols, polypeptides, and oligosaccharides modulate inflammation and immunity by altering the composition of gut microbiota. The polyphenols and polypeptides in Chinese rice wine have protective effects against cardiovascular disease. In this study, we hypothesized that the polyphenols, polypeptides, and oligosaccharides in Chinese rice wine can ameliorate diabetic cardiomyopathy (DCM) by altering gut microbiota and metabolites.MethodsMice with DCM and high glucose cells were treated with rice wine polyphenols (RWPH), rice wine polypeptides (RWPE), and rice wine oligosaccharides. Cardiac function was evaluated by echocardiography and detection of myocardial injury markers. We observed the pathological structures using hematoxylin and eosin staining, Masson's trichrome staining, and transmission electron microscopy. The expression levels of autophagy-related proteins and stubRFP-sensGFP-LC3 fluorescence were measured to evaluate autophagy. We performed TUNEL staining and measured the levels of Bax, Bcl-2, and p53 to assess apoptosis. To analyze the effects of the rice wine functional components on the gut microbiota and metabolites of DCM mice, we performed fecal 16S-rDNA gene sequencing and serum untargeted metabolomics.ResultsOur results showed an increase in cardiac and mitochondrial function, promotion of autophagy, and inhibition of cardiomyocyte apoptosis, which indicates that RWPH and RWPE can ameliorate DCM. The abundance of Akkermansia and Desulfovibrio were reduced by the presence of RWPH and RWPE. The growth of the Lachnospiraceae_NK4A136_group and Clostridiales-unclassified were promoted by the presence of RWPH. Tryptophan metabolism-associated metabolites were increased and phenylalanine levels were reduced by the presence of RWPH and RWPE. The biosynthesis of primary bile acids was enhanced by the presence of RWPH.ConclusionBoth RWPH and RWPE provided a protective effect against DCM by promoting autophagy, inhibiting apoptosis, and reversing both gut microbiota dysbiosis and metabolic dysregulation.

Takostubo syndrome combined with ventricular septal perforation: a case report

BackgroundThe precise clinical features and etiologic basis of Takotsubo syndrome remain unclear, although an association with emotional or stressful triggers has been recognized. Ventricular septal perforation is a very rare life-threatening complication.Case presentationA 77-year-old female patient presented to the hospital with unrelieved chest tightness and shortness of breath. Three months ago, the patient's electrocardiogram revealed ischemic T wave inversion of the anterior wall, along with an increase in myocardial injury markers. There was no evidence of a ventricular septal defect on echocardiography. The patient was admitted to the respiratory department to treat lung lesions. The electrocardiogram demonstrated dynamic changes following admission, and the myocardial markers returned to normal, but the echocardiography revealed a ventricular septal defect. The initial diagnosis was ventricular septal perforation because of myocardial infarction with acute anterior ST-segment elevation. Coronary angiography revealed no abnormalities, but left ventricular angiography revealed an enlarged apex and VSD, with a right ventricular shunt bundle. Later, cardiac MRI revealed an apical ventricular septal defect. Further inquiry of the patient's medical history revealed that her husband died unexpectedly three months ago, and her daughter was seriously injured in a car accident, causing the patient severe emotional distress. Takotsubo syndrome was then determined in conjunction with the patient's medical history, symptoms, signs, and pertinent examinations. Without using a catheter or a surgical procedure, we managed the patient's medical condition. Two weeks later, the patient was discharged with symptoms improved.ConclusionsTakotsubo syndrome is comparable to an acute myocardial infarction on clinical and electrocardiographic examination in the absence of significant coronary disease. Although ventricular septal perforation is most commonly associated with acute myocardial infarction, it can also happen following Takotsubo syndrome. Takotsubo syndrome complicated by ventricular septal perforation is easily misdiagnosed. The early recognition and management of this condition can avoid or reduce morbidity and mortality.

415.4: Ischemia Minimization Improves Cardiac Function in an Ex Vivo Xeno Working Heart Model

Introduction: Previous studies showed that ischemia minimization (IM), accomplished by perfusing the heart xenograft during storage, prevents ‘initial cardiac xenograft dysfunction’ (ICXD) and enables prolonged survival following orthotopic cardiac xenotransplantation. Here we report initial observations in a model designed to evaluate effects on heart performance associated with IM and genetic modifications targeted to address xeno-injury mechanisms in a working ex vivo model of ICXD. Method: Hearts from genetically modified and wildtype (WT) pigs were procured after flushing with cold preservation solution (UW, 4oC) and stored for 3 hours either in cold saline (0.9%, 4oC: cold storage (CS)) or were perfused with oxygenated STEEN Solution with RBCs (IM). IM perfusion at 40 mmHg was initiated at room temperature for 20 minutes to facilitate homogeneous graft perfusion before cooling to 4oC for the remainder of the storage period. The genetically modified hearts either had combined knockouts of three specific xenogeneic carbohydrate genes (GTKO, CMAHKO, b4GALNT2KO: TKO) with variable expression of human transgenes (hTG) including complement and thrombo-regulatory proteins (n=29); or GTKO with additional expression of hCD55 (GTKO.hCD55; n=3). Heart function and laboratory parameters were assessed at specific timepoints on a working heart rig while perfused with freshly collected heparinized whole human blood. Troponin I was used as a marker for myocardial injury. Results: In total, 41 hearts were perfused ex vivo, 23 after CS (TKO + hTG n=14, GTKO.hCD55 n=2, WT n=7), and 18 after IM (TKO + hTG n=15, GTKO.hCD55 n=1, WT n=2). Cardiac output (mL/min) was significantly improved for the IM group at all loading conditions relative to CS, (see figure 1). There was a strong trend toward reduced troponin I release, particularly within the first 60 minutes of perfusion (see figure 2). Conclusion: IM is protective with respect to cardiac function following pig heart ischemia and subsequent reperfusion with human blood in an ex vivo model of heart xenotransplantation. The hypothesis that variation in physiologic and biochemical outcomes within groups is influenced by variable expression of complement and coagulation pathway regulatory genes is being investigated.

Experimental study of mitochondrion-targeted small molecule IR-61 ameliorated exhaustive exercise-induced cardiac injury in rats

To investigate the effects of mitochondrion-targeted cyanine fluorescent small molecule IR-61 on cardiac injury induced by exhaustive exercise in rats. Thirty-six adult male SD rats were randomly divided into 3 groups(n=12),control group (Ctrl), exhaustive exercise group (EE) and IR-61+ exhaustive exercise group (IR-61+EE). IR-61+EE group were intraperitoneally injected with 2 mg/kg IR-61 at the same time on day 1, 4 and 7. One hour after the end of the last drug administration, the two exhaustive exercise groups were subjected to exhaustive exercise modeling. The rats were placed on an animal treadmill with a slope of 0° at a speed of 10~15 m/min to coordinate their limbs running posture, and then ran at a speed of 25~30 m/min until exhaustion about 15 minutes later. After the animal models established, ECG was recorded by physiological recorder, myocardial injury was observed by light microscope, mitochondrial injury was observed by transmission electron microscope, myocardial cell apoptosis was detected by TUNEL method, markers of myocardial injury were detected by ELISA, and myocardial mitochondrial respiration rate was measured by high-resolution Oxygraph-2K mitochondrial instrument. ① Compared with Ctrl group, heart rate was increased, PR interval was shortened, QRS interval was prolonged, QTc was prolonged and ST segment was depressed significantly in EE group (P＜0.05). In EE group, myocardial fiber fracture and mitochondrial inner chamber swelling were obvious, mitochondrial crest was fuzzy, mitochondrial outer membrane was incomplete, and a large number of mitochondrial rupture and fusion were visible. In EE group, TUNEL staining cells were abundant, chromatin concentration and marginalization, nuclear membrane lysis, chromatin fragmentation into massive apoptotic bodies, apoptosis score increased (P＜0.05). The levels of creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I(cTn-I) and N-terminal B-type natriuretic peptide (NT-proBNP) were increased in EE group (P＜0.05). Basal respiration rate, oxidative respiration rate of fatty acids and respiration rate of complex Ⅰ, Ⅱ and Ⅳ were all decreased (P＜ 0.05). ② Compared with EE group, the heart rate in IR-61+EE group was increased, PR interval was prolonged, QRS interval was shortened, QTc was shortened, ST segment was not significantly depressed (P＜0.05). In IR-61+EE group, myocardial fiber arrangement was loose, no obvious fracture was observed, mitochondrial inner ventricle was swelling, mitochondrial outer membrane was intact, TUNEL stained cells and unstained cells were observed, the overall morphology was more similar to Ctrl group. Apoptosis index was decreased (P＜0.05), the levels of CK-MB and cTn-I were decreased in IR-61+EE group (P＜0.05). The oxidative respiration rate of fatty acids and the respiration rate of complex Ⅱ and Ⅳ were increased (P＜0.05). Mitochondrion-targeted cyanine fluorescent small molecule IR-61 can improve cardiac electrical activity, reduce myocardial cell injury and mitochondrial injury, reduce myocardial cell apoptosis, and improve the myocardial mitochondrial energy metabolism condition in exhausted rats.

2-Aminoethoxydiphenyl-borate reduces arsenic-induced cardiotoxicity in rats.

Objective To study the effect of 2-Aminoethoxydiphenyl-borate (2-APB) on arsenic-induced cardiotoxicity. Methods 32 male Specific Pathogen Free (SPF) grade Sprague Dawley (SD) rats are randomly divided into 4 groups: control group, natural recovery group after arsenic poisoning (sodium arsenite, NaAsO2 group), low dose 2-APB treatment group after arsenic poisoning (L-2-APB group) and high dose 2-APB treatment group after arsenic poisoning (H-2-APB group) (n = 8 per group). After establishing the rat model, all rats are examined by echocardiography to obtain global longitudinal strain (GLS) parameters. Then, all rats are killed to obtain serum and heart samples. The morphological changes of cardiomyocytes are observed by hematoxylin-eosin (HE) staining. And the levels of serum markers of myocardial injury and the indexes related to oxidative stress and apoptosis are measured. Results In this study, compared with the control group, the NaAsO2 group has decreased absolute value of GLS, Superoxide dismutase (SOD), Glutathione peroxidase (GSH-px) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity, and Bcl-2 levels, increased serum Creatine Kinase Myocardial Band (CKMB), serum Lactate Dehydrogenase (LDH), Malonic dialdehyde (MDA) and cleaved caspase-3 activity, and Bax levels (P＜0.05). Furthermore, 2-APB led to dose-dependent increase in absolute values of GLS-endo and GLS-mid, SOD, GSH-px and SERCA activity, and Bcl-2 levels, decrease serum CKMB and LDH, MDA and cleaved caspase-3 activity, and Bax levels compared with the NaAsO2 group (P＜0.05). Conclusion 2-APB can reduce the degree of arsenic-induced cardiotoxicity.

Tanshinone IIA reduces pyroptosis in rats with coronary microembolization by inhibiting the TLR4/MyD88/NF-κB/NLRP3 pathway.

Pyroptosis is an inflammatory form of programmed cell death that is linked with invading intracellular pathogens. Cardiac pyroptosis has a significant role in coronary microembolization (CME), thus causing myocardial injury. Tanshinone IIA (Tan IIA) has powerful cardioprotective effects. Hence, this study aimed to identify the effect of Tan IIA on CME and its underlying mechanism. Forty Sprague–Dawley (SD) rats were randomly grouped into sham, CME, CME + low-dose Tan IIA, and CME + high-dose Tan IIA groups. Except for the sham group, polyethylene microspheres (42 µm) were injected to establish the CME model. The Tan-L and Tan-H groups received intraperitoneal Tan IIA for 7 days before CME. After CME, cardiac function, myocardial histopathology, and serum myocardial injury markers were assessed. The expression of pyroptosis-associated molecules and TLR4/MyD88/NF-κB/NLRP3 cascade was evaluated by qRT-PCR, Western blotting, ELISA, and IHC. Relative to the sham group, CME group's cardiac functions were significantly reduced, with a high level of serum myocardial injury markers, and microinfarct area. Also, the levels of caspase-1 p20, GSDMD-N, IL-18, IL-1β, TLR4, MyD88, p-NF-κB p65, NLRP3, and ASC expression were increased. Relative to the CME group, the Tan-H and Tan-L groups had considerably improved cardiac functions, with a considerably low level of serum myocardial injury markers and microinfarct area. Tan IIA can reduce the levels of pyroptosis-associated mRNA and protein, which may be caused by inhibiting TLR4/MyD88/NF-κB/NLRP3 cascade. In conclusion, Tanshinone IIA can suppress cardiomyocyte pyroptosis probably through modulating the TLR4/MyD88/NF-κB/NLRP3 cascade, lowering cardiac dysfunction, and myocardial damage.

7-Hydroxyflavone Alleviates Myocardial Ischemia/Reperfusion Injury in Rats by Regulating Inflammation.

Inflammation is the primary pathological process of myocardial ischemia/reperfusion injury (MI/RI). 7-Hydroxyflavone (HF), a natural flavonoid with a variety of bioactivities, plays a crucial role in various biological processes. However, its cardioprotective effects and the underlying mechanisms of MI/RI have not been investigated. This study aimed to explore whether pretreatment with HF could attenuate MI/RI-induced inflammation in rats and investigate its potential mechanisms. The results showed that pretreatment with HF could significantly improve the anatomic data and electrocardiograph parameters, reduce the myocardial infarct size, decrease markers of myocardial injury (aspartate transaminase, creatine kinase, lactate dehydrogenase, and cardiac troponin I), inhibit inflammatory cytokines (IL-1β, IL-6, and TNF-α), suppress oxidative stress, and recover the architecture of the cardiomyocytes. The cardioprotective effect of HF was connected with the regulation of the MAPK/NF-κB signaling pathway. What is more, molecular docking was carried out to prove that HF could be stably combined with p38, ERK1/2, JNK, and NF-κB. In summary, this is a novel study demonstrating the cardioprotective effects of HF against MI/RI in vivo. Consequently, these results demonstrate that HF can be considered a promising potential therapy for MI/RI.

High-sensitivity troponin T in preterm infants with a hemodynamically significant patent ductus arteriosus

Background: The incidence of patent ductus arteriosus (PDA) is inversely related to gestational age. Cardiac troponin T (cTnT) is a specific marker for myocardial ischemic injury. The aim of this work was to investigate if a hemodynamically significant patent ductus arteriosus leads to elevated high- sensitivity troponin T (hsTnT) levels in serum. Methods: This prospective observational research included 60 preterm infants <34 weeks’ gestation, weighing <1500 g with PDA. Patients were classified into two groups according to the ECHO findings: Group A: preterm infants who had hs.PDA (PDA >1.5 mm and LA: Ao >1.2 and group B: preterm infants without hs.PDA. All cases were subjected to clinical examination, echocardiogram and hsTnT assay. Results: Serum hsTnT levels was significantly elevated in patients with hs PDA compared to patients without hs PDA. High sensitive T-troponin can significantly detect hsPDA with AUC of 0.986, P value <0.001. At cut off >100 pg/ml, it’s a significant detector with sensitivity of 93.33%, specificity of 90%, PPV of 90.3, NPV of 93.1 and diagnostic accuracy of 91.5%. PDA had a significant positive correlation with hsTnT (r=0.803, P<0.001). Conclusions: HsTnT can significantly detect hemodynamically significant PDA in preterm infants with high sensitivity and specificity.

Hsp72-Based Effect and Mechanism of Microwave Radiation-Induced Cardiac Injury in Rats.

The purpose of this study was to determine the role of heat shock protein 72 (Hsp72) changes in cardiac injury caused by microwave radiation, aimed at providing novel insights into the mechanism of this damage. A digital thermometer was used to measure the rectal temperature of the rats' pre- and post-radiation. On the 1st, 7th, 14th, and 28th days post-radiation, the changes in electrocardiogram (ECG) were analyzed by a multi-channel physiological recorder. The myocardial enzyme activities and ion concentrations were detected by an automatic biochemical analyzer. Additionally, the levels of myocardial injury markers were established by the enzyme-linked immunosorbent assay (ELISA), and those of hormones were measured by radioimmunoassay. The structure and ultrastructure of the myocardial tissue were observed using an optical microscope and transmission electron microscopy (TEM). The expression of Hsp72 was measured by Western blot and immunofluorescence analyses. Post-exposure, the rectal temperature in the R-group increased significantly, ECG was disordered, and the concentrations of ions were decreased. Furthermore, the activities of myocardial enzymes were changed, and the contents of myocardial injury markers and hormones were increased. We observed damage to the structure and ultrastructure and significantly increased expression of Hsp72. As a whole, the results indicated that S-wave microwave radiation at 30 mW/cm2 for 35 min resulted in damage to the cardiac functionality organigram, caused by a combination of the thermal and nonthermal effects.

The Relationship between Selected Inflammation and Oxidative Stress Biomarkers and Carotid Intima-Media Thickness (IMT) Value in Youth with Type 1 Diabetes Co-Existing with Early Microvascular Complications.

Recent years have confirmed the importance of oxidative stress and biomarkers of inflammation in estimating the risk of cardiovascular disease (CVD) and explaining not fully understood pathogenesis of diabetic macroangiopathy. We aimed to analyze the relation between the intima-media thickness (IMT) of common carotid arteries and the occurrence of classical cardiovascular risk factors, together with the newly proposed biomarkers of CVD risk (high-sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), adiponectin, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and vitamin D) in youth with type 1 diabetes (T1D) recognized in screening tests to present early stages of microvascular complications (VC). The study group consisted of 50 adolescents and young adults with T1D, mean age 17.1 years (10–26 age range), including 20 patients with VC (+) and 30 VC (−). The control group (Control) consisted of 22 healthy volunteers, mean age 16.5 years (11–26 age range). In the VC (+) patients, we found a significantly higher concentration of HbA1c, lipid levels, hsCRP and NT-proBNP. BMI and blood pressure values were highest in the VC (+) group. Higher levels of MPO and lower levels of vitamin D were found in both diabetic groups vs. Control. IMT in VC (+) patients was significantly higher and correlated positively with HbA1c, hsCRP, NT-pro-BNP and negatively with vitamin D levels. In conclusion, youth with T1D and VC (+) present many abnormalities in the classical and new CVD biomarkers. hsCRP and MPO seem to be the most important markers for estimating the risk of macroangiopathy. NT-proBNP may present a possible marker of early myocardial injury in this population.

The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury.

(1) Background: The present study aims to investigate the effect of administration of Levosimendan and Exenatide in various concentrations, as well as of the coadministration of those agents in an ischemia–reperfusion injury isolated heart model. (2) Methods: After 30 min of perfusion, the hearts underwent a 30 min period of regional ischemia followed by a 120 min period of reperfusion. All animals were randomly divided into 12 experimental groups of nine animals in each group: (1) Control, (2) Sham, (3) Digox (Negative control, Digoxin 1.67 μg/min), (4) Levo 1 (Levosimendan 0.01 μg/min), (5) Levo 2 (Levosimendan 0.03 μg/mL), (6) Levo 3 (Levosimendan 0.1 μg/min), (7) Levo 4 (Levosimendan 0.3 μg/min), (8) Levo 5 (Levosimendan 1 μg/min), (9) Exen 1 (Exenatide 0.001 μg/min), (10) Exen 2 (Exenatide 0.01 μg/min), (11) Exen 3 (Exenatide 0.1 μg/min) and (12) Combi (Levosimendan 0.1 µg/mL + Exenatide 0.001 μg/min). The hemodynamic parameters were recorded throughout the experiment. Arrhythmias and coronary flow were also evaluated. After every experiment the heart was suitably prepared and infarct size was measured. Markers of myocardial injury were also measured. Finally, oxidative stress was evaluated measuring reactive oxygen species. (3) Results: A dose-dependent improvement of the haemodynamic response was observed after the administration of both Levosimendan and Exenatide. The coadministration of both agents presented an even greater effect, improving the haemodynamic parameters further than the two agents separately. Levosimendan offered an increase of the coronary flow and both agents offered a reduction of arrhythmias. A dose-dependent reduction of the size of myocardial infarction and myocardial injury was observed after administration of Levosimendan and Exenatide. The coadministration of both agents offered a further improving the above parameters. Levosimendan also offered a significant reduction of oxidative stress. (4) Conclusions: The administration of Levosimendan and Exenatide offers a significant benefit by improving the haemodynamic response, increasing the coronary flow and reducing the occurrence of arrhythmias, the size of myocardial injury and myocardial oxidative stress in isolated rat hearts.

Glucose tolerance and markers of myocardial injury after an acute coronary syndrome: predictive role of the 1-h plus 2-h plasma glucose at the oral glucose tolerance test

ObjectiveImpaired glucose tolerance (IGT) has been related to adverse cardiovascular outcomes. We investigated the added value of 1-h plasma glucose (PG) at the oral glucose tolerance test (OGTT) in predicting admission and peak cardiac high-sensitivity troponin T (hs-TnT) and NT-proBNP values in IGT patients admitted for an acute coronary syndrome (ACS).Research design and methodsAmong 192 consecutive ACS patients, 109 had Hb1Ac and fasting plasma glucose negative for newly diagnosed diabetes. Upon OGTT performed > 96 h after admission, 88, conventionally diagnosed as IGT, were divided into: “full glucose tolerance” (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 12);”early IGT” (1 h-PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 33);”late IGT” (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 8); and “full IGT” (1-h PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 35). The 4 groups were compared for cardiac markers.ResultsThe first three groups had similar cardiac marker values, but only full IGT patients had significantly higher admission hs-TnT compared with the 3 other groups [median (interquartile range): 911 (245-2976) vs 292 (46-1131), P < 0.001]. Full IGT patients also had higher hs-TnT peak compared with fully glucose tolerant and early IGT patients. Only full IGT patients had longer hospitalization and higher NT-proBNP vs fully glucose tolerant patients (P = 0.005).ConclusionsAmong non-diabetic ACS patients, only those with both 1-h PG ≥ 155 mg/dL and 2-h PG ≥ 140 mg/dL had more severe myocardial injury and longer hospitalization. One-h PG-OGTT importantly contributes to assessing post-ACS cardiac risk.

Circulating MicroRNAs and myocardial involvement severity in chronic Chagas cardiomyopathy.

BackgroundChronic Chagas Cardiomyopathy (CCM) is characterized by a unique pathophysiology in which inflammatory, microvascular and neuroendocrine processes coalesce in the development of one of the most severe cardiomyopathies affecting humans. Despite significant advances in understanding the molecular mechanisms involved in this disease, scarce information is available regarding microRNAs and clinical parameters of disease severity. We aimed to evaluate the association between circulating levels of six microRNAs with markers of myocardial injury and prognosis in this population.MethodsPatients with CCM and reduced ejection fraction were included in a prospective exploratory cohort study. We assessed the association of natural log-transformed values of six circulating microRNAs (miR-34a-5p, miR-208a-5p, miR-185-5p, miR-223-5p, let-7d-5p, and miR-454-5p) with NT-proBNP levels and echocardiographic variables using linear regression models adjusted for potential confounders. By using Cox Proportional Hazard models, we examined whether levels of microRNAs could predict a composite outcome (CO), including all-cause mortality, cardiac transplantation, and implantation of a left ventricular assist device (LVAD). Finally, for mRNAs showing significant associations, we predicted the target genes and performed pathway analyses using Targetscan and Reactome Pathway Browser.ResultsSeventy-four patients were included (59% males, median age: 64 years). After adjustment for age, sex, body mass index, and heart failure medications, only increasing miR-223-5p relative expression levels were significantly associated with better myocardial function markers, including left atrium area (Coef. -10.2; 95% CI -16.35; -4.09), end-systolic (Coef. -45.3; 95% CI -74.06; -16.61) and end-diastolic volumes (Coef. -46.1; 95% CI -81.99; -10.26) of the left ventricle. Moreover, we observed that higher miR-223-5p levels were associated with better left-ventricle ejection fraction and lower NT-proBNP levels. No associations were observed between the six microRNAs and the composite outcome. A total of 123 target genes for miR-223-5p were obtained. From these, several target pathways mainly related to signaling by receptor tyrosine kinases were identified.ConclusionsThe present study found an association between miR-223-5p and clinical parameters of CCM, with signaling pathways related to receptor tyrosine kinases as a potential mechanism linking low levels of miR-223-5p with CCM worsening.

Single-Dose St. Thomas Versus Custodiol® Cardioplegia for Right Mini-thoracotomy Mitral Valve Surgery

ObjectiveCustodiol® and St. Thomas cardioplegia are widely employed in mini-thoracotomy mitral valve (MV) operations. One-dose of the former provides 3 h of myocardial protection. Conversely, St. Thomas solution is usually reinfused every 30 min and safety of single delivery is unknown. We aimed to compare single-shot St. Thomas versus Custodiol® cardioplegia.MethodsPrimary endpoint of the prospective observational study was cardiac troponin T level at different post-operative time-points. Propensity-weighted treatment served to adjust for confounding factors.ResultsThirty-nine patients receiving St. Thomas were compared with 25 patients receiving Custodiol® cardioplegia; cross-clamping always exceeded 45 min. No differences were found in postoperative markers of myocardial injury. Ventricular fibrillation at the resumption of electric activity was more frequent following Custodiol® cardioplegia (P = .01).ConclusionEffective myocardial protection exceeding 1 h of ischemic arrest can be achieved with a single-dose St. Thomas cardioplegia in selected patients undergoing right mini-thoracotomy MV surgery.

Epigenetic modification mechanism of histone demethylase KDM1A in regulating cardiomyocyte apoptosis after myocardial ischemia-reperfusion injury.

Hypoxia and reoxygenation (H/R) play a prevalent role in heart-related diseases. Histone demethylases are involved in myocardial injury. In this study, the mechanism of the lysine-specific histone demethylase 1A (KDM1A/LSD1) on cardiomyocyte apoptosis after myocardial ischemia-reperfusion injury (MIRI) was investigated. Firstly, HL-1 cells were treated with H/R to establish the MIRI models. The expressions of KDM1A and Sex Determining Region Y-Box Transcription Factor 9 (SOX9) in H/R-treated HL-1 cells were examined. The cell viability, markers of myocardial injury (LDH, AST, and CK-MB) and apoptosis (Bax and Bcl-2), and Caspase-3 and Caspase-9 protein activities were detected, respectively. We found that H/R treatment promoted cardiomyocyte apoptosis and downregulated KDM1A, and overexpressing KDM1A reduced apoptosis in H/R-treated cardiomyocytes. Subsequently, tri-methylation of lysine 4 on histone H3 (H3K4me3) level on the SOX9 promoter region was detected. We found that KDM1A repressed SOX9 transcription by reducing H3K4me3. Then, HL-1 cells were treated with CPI-455 and plasmid pcDNA3.1-SOX9 and had joint experiments with pcDNA3.1-KDM1A. We disclosed that upregulating H3K4me3 or overexpressing SOX9 reversed the inhibitory effect of overexpressing KDM1A on apoptosis of H/R-treated cardiomyocytes. In conclusion, KDM1A inhibited SOX9 transcription by reducing the H3K4me3 on the SOX9 promoter region and thus inhibited H/R-induced apoptosis of cardiomyocytes.

Longitudinal evaluation of diastolic dyssynchrony by SPECT gated myocardial perfusion imaging early after acute myocardial infarction and the relationship with left ventricular remodeling progression in a swine model

BackgroundLeft ventricular diastolic dyssynchrony (LVDD), a dyssynchronous relaxation pattern, has been known to develop after myocardial damage. We aimed to evaluate the dynamic changes in LVDD in the early stage of acute myocardial infarction (AMI) by phase analysis of 99mtechnetium methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) and explore its relationship with the progression of left ventricular remodeling (LVR). MethodsThe left anterior descending coronary arteries of 16 Bama miniature swine were occluded with a balloon to build AMI models. Animals were imaged by SPECT GMPI before AMI and at 1 day, 1 week and 4 weeks after AMI, and quantitative analysis was performed to determine the extent of left ventricle (LV) perfusion defects, left ventricular systolic dyssynchrony (LVSD) and the LVDD parameters: phase histogram bandwidth (PBW) and phase standard deviation (PSD). Echocardiography was simultaneously applied to evaluate left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the LVDD parameters: Te-12-diff and Te-12-SD. Myocardial injury markers were measured, and 12-lead ECGs were performed. The degree of LVR progression was defined as ΔLVESV (%) = (LVESVAMI4weeks − LVESVAMI1day)/LVESVAMI1day. ResultsThirteen swine completed the study. LVDD parameters changed dynamically at different time points after AMI. LVDD occurred as early as 1 day after AMI, peaked at 1 week, and trended toward a partial recovery at 4 weeks. Phase analysis on SPECT GMPI showed a significant correlation with tissue Doppler imaging for the assessment of LVDD during the longitudinal evaluation (r = 0.569 to 0.787, both P <0.05). During the univariate and multivariate regression analyses, the LVDD parameters PBW and PSD as of 1 day after AMI were significantly associated with the progression of LVR, respectively (PBW, β = 0.004, 95% CI 0.001 to 0.007, P = 0.024; PSD, β = 0.008, 95% CI 0.000 to 0.017, P = 0.049). Adjusted smooth curve fitting and threshold effect analysis indicated PBW and PSD break-point values of 142° and 60.4°, respectively, to predict the progression of LVR after AMI. ConclusionsPhase analysis of SPECT GMPI can accurately and reliably characterize LVDD. LVDD occurred on the first day after AMI, reached its peak at 1 week, and partially recovered at 4 weeks after AMI. LVDD as evaluated by phase analysis of SPECT GMPI early after AMI was significantly associated with the progression of LVR. The early assessment of LVDD after AMI may provide helpful information for predicting the progression of LVR in the future.

Plasma levels of thrombin and activated protein C in patients with acute myocardial Infarction: An observational study.

IntroductionActivation of the plasmatic coagulation system is a major contributor to acute myocardial infarction (AMI). Markers of plasmatic coagulation and thrombin activation are correlated with clinical, laboratory and outcome parameters. In this study, we sought to evaluate if the catalytically active coagulation factors thrombin and activated protein C (APC) can be measured in patients with AMI and whether there are associations with laboratory or clinical parameters.MethodsThrombin and APC was quantified using oligonucleotide-enzyme-capture assays (OECAs) in 132 patients presenting with AMI immediately before and 24 h after percutaneous coronary intervention (PCI).ResultsAPC was measured above the lower limit of quantification (LLOQ) in 43 (32.6%) patients before PCI (day 0) and in 55 (41.7%) patients on the following day (day 1). Thrombin was measured in 62 (47.0%) patients on day 0 and 60 (45.5%) on day 1. Both APC and thrombin were correlated with markers of thrombin generation including F1 + 2 and TAT. Additionally, APC values correlated with CK and CK-MB while thrombin correlated with CK and troponin I after PCI. APC levels above a cutoff of 0.141 ng/ml after PCI, but not thrombin, predicted 30 day major adverse cerebrovascular events.ConclusionBoth thrombin and APC were elevated above the LLOQ in a subset of patients with AMI before and after PCI and correlated with surrogate markers of myocardial injury. Our results indicate that enzymatically active APC and thrombin are present in the circulation of patients with AMI.

Chaihujialonggumulitang shows psycho-cardiology therapeutic effect on acute myocardial infarction with comorbid anxiety by the activation of Nrf2/HO-1 pathway and suppression of oxidative stress and apoptosis

BackgroundAnxiety is a common comorbidity of cardiovascular diseases, which deteriorated cardiac function. Chaihujialonggumulitang (BFG) was reported to have antioxidant properties, alleviate myocardial ischemia injury and improve anxiety-like behavior. The Nuclear factor erythroid 2-related factor 2 (Nrf2) /heme oxygenase-1 (HO-1) pathway is the main mechanism to defend against oxidative stress, and improve cardiac function. This study was to investigate the possible mechanism of BFG in the treatment of psycho-cardiology. MethodsAMI with comorbid anxiety rat model was established by ligation of the left anterior descending coronary artery combined with uncertain empty bottle stimulation, followed by the administration of BFG (1 mL/100 g/d by gavage) or Dimethyl fumarate (DMF, 10 mg/kg/d by intraperitoneal injection) for 6 days. Echocardiography, myocardial injury markers, H&E, and Masson staining were employed to evaluate cardiac function. Behavioral tests and hippocampus neurotransmitters were applied to record anxiety-like behavior. We employed immunohistochemistry, RT-PCR, western blotting, and biochemical analysis to detect the protein and gene expression of Nrf2/HO-1 pathway-related factors, and oxidative stress and apoptosis parameters. ResultsRats in the AMI and complex groups showed cardiac function deterioration, as well as anxiety-like behavior. BFG improved echocardiography indicators, reduced myocardial injury markers, and attenuated myocardial pathological changes. BFG also ameliorated anxiety-like behaviors and elevated neurotransmitters levels. BFG promoted the activation of Nrf2/HO-1 pathway, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. DMF showed therapeutic effects and molecular mechanisms similar to BFG. ConclusionBFG may possess a psycho-cardiology therapeutic effect on AMI with comorbid anxiety by the activation of the Nrf2/HO-1 pathway and suppression of oxidative stress and apoptosis.