Serum cTnI Research Articles

Clinical Effect of Qili Qiangxin Capsule Combined with Sacubitril-Valsartan in Patients with Chronic Heart Failure.

The clinical effect of Qili Qiangxin capsule combined with sacubitril-valsartan on patients with chronic heart failure was studied. We selected 108 patients with chronic heart failure in our hospital from March 2016 to January 2020 and divided them into a control group and a study group according to the random table method, with 54 cases in each. The control group took sacubitril and valsartan orally, and the study group took Qili Qiangxin pill on the basis of sacubitril and valsartan. The course of the treatment for 2 groups is 4 weeks. We compared the total effective rate of the treatment of the 2 groups for 4 weeks, cardiac function (left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF)) before and after 4 weeks of treatment, 6 min walking distance (6MWT), changes in cTnI and NT-proBNP levels, and adverse reactions. The total effective rate in the study group (90.74%) is higher than that in the control group (72.22%) (P＜0.05). After 4 weeks of treatment, the study group LVESV (45.23 ± 2.98 mm) and LVEDV (43.38 ± 4.01 mm) are lower than those of the control group ((49.98 ± 2.56 mm) and (50.75 ± 3.49 mm), respectively), while LVEF (47.38 ± 2.78%) is higher than that in the control group (42.08 ± 3.24%) (P ＜ 0.05). After 4 weeks of treatment, the study group 6MWT (476.58 ± 31.25 m) of patients with chronic heart failure is higher than that of the control group (396.52 ± 24.52 m) (P ＜0.05). After 4 weeks of treatment, the study group serum cTnI (0.36 ± 0.12 μg/L) and NT-proBNP (276.91 ± 30.12 pg/ml) of patients with chronic heart failure are lower than those in the control group (0.87 ± 0.25 μg/L) and (367.48 ± 48.57 pg/ml) (P＜0.05). There is no significant difference between the adverse reactions in the two groups (P ＞ 0.05). Conclusion: Xinbao pills combined with sacubitril and valsartan have a good effect on patients with chronic heart failure, which can improve the heart function and exercise endurance and reduce serum cTnI and NT-proBNP levels.

Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway.

The present study aimed to evaluate the effects of hypercholesterolemia on cardioprotection of ischemic preconditioning and α7 nicotinic acetylcholine receptor (α7nAChR) agonist postconditioning and explore the potential mechanisms that hypercholesterolemia affected their cardioprotection. Hypercholesterolemic and normal rats were divided into the four groups that received the following treatments: i) Hypercholesterolemic control and normal control groups; ii) hypercholesterolemic ischemia/reperfusion (HI) and normal ischemia/reperfusion (NI) groups; iii) hypercholesterolemic ischemic preconditioning (HIPC) and normal ischemic preconditioning (NIPC) groups; and iv) hypercholesterolemic PNU282987 postconditioning (HPNU) and normal PNU282987 postconditioning (NPNU) groups. Serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels after ischemia/reperfusion were assayed. Furthermore, infarct size and expression levels of Akt, phosphorylated (p)-Akt and endothelial nitric oxide synthase (eNOS) in ischemic myocardium were assessed. Compared with the NI group, serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased, and myocardial p-Akt/Akt and eNOS/GAPDH ratios were significantly increased in the NIPC and NPNU groups. Compared with the HI group, serum CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased in the HIPC group; however, myocardial p-Akt/Akt and eNOS/GAPDH ratios did not significantly change in the HIPC group. Furthermore, there were no significant difference between the HI and HPNU groups in serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels, infarct size, myocardial p-Akt/Akt and eNOS/GAPDH ratios. In conclusion, hypercholesterolemia could aggravate myocardial ischemia/reperfusion injury, attenuate cardioprotection of ischemic preconditioning and eliminate cardioprotection from α7nAChR agonist postconditioning by enhancing inflammation and inhibiting PI3K/Akt/eNOS pathway.

LuQi Formula Ameliorates Myocardial Fibrosis by Suppressing TLR4/MyD88/NF-κB Pathway and NLRP3 Inflammasome Activation in Mice with Myocardial Infarction.

Background Myocardial fibrosis caused by myocardial infarction (MI) is the key factor leading to cardiac remodeling; nod-like receptor family pyrin domain-containing 3 (NLRP3) plays an important role in regulation of myocardial injury; however, its relationship with TLR4/MyD88/NF-κB signaling pathway is largely unreported. In recent years, traditional Chinese medicine (TCM) prevention and treatment of cardiovascular diseases has shown its unique advantages and broad application prospects. LuQi Formula (LQF) has been used for more than 20 years in Shuguang Hospital (Shanghai, China), and it was confirmed that it can improve the clinical symptoms of patients after MI. Here, we investigated the mechanism of LQF by suppressing NLRP3 inflammasome activation and TLR4/MyD88/NF-κB pathway in mice with MI. Purpose The purpose of this study was to verify the positive effects of the LQF in ameliorating myocardial fibrosis and inflammasome infiltration in the MI mice in vivo. Methods Forty mice were randomized into four groups: the sham group, the MI group, the LQF group, and the perindopril group (n = 10 per group). Left anterior descending (LAD) coronary artery ligation was performed in all groups except the sham group. The mice were treated with LQF after MI. After 4 weeks, LDH, cTnI, IL-1β, and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) kit, and cardiac function was evaluated by echocardiography. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the myocardial injury and fibrosis. Western blot was used to evaluate the expression of collagen I, α-SMA, NLRP3 inflammasome, and TLR4/MyD88/NF-κB signaling pathway. Immunohistochemical analysis was used to further detect the expression of Fibronectin, α-SMA, collagen I, collagen III, NLRP3, and NF-κB in myocardial tissue. Results Compared with the MI group, the ejection fraction (EF) and fractional shortening (FS) in the LQF group were significantly improved, while the left ventricular end diastolic diameter (LVEDd) and left ventricular internal dimension systole (LVIDs) were significantly decreased. The representative staining of H&E and Masson showed that treatment with LQF could effectively reduce myocardial injury and fibrosis. ELISA results showed that serum LDH, cTnI, TNF-α, IL-18, and IL-1β in LQF group were significantly lower than those in MI group. The western blot results showed that the expressions of collagen I and α-SMA were decreased significantly in the LQF group. Moreover, the expressions of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathway were downregulated in the LQF treatment group. Conclusion Our results suggested that LQF could significantly improve cardiac function and ameliorate myocardial fibrosis. In addition, we found that LQF could downregulate the TLR4/MyD88/NF-κB signaling pathway and then inhibit the activation of NLRP3 inflammasome, suggesting that LQF alleviated cardiac fibrosis by decreasing the TLR4/MyD88/NF-κB signaling pathway and then inhibited NLRP3 inflammasome activation in MI mice, which indicates potential therapeutic effect of LQF on patients with MI.

Serum cardiac troponin I is a candidate biomarker for cardiomyopathy in Duchenne and Becker muscular dystrophies.

Serum cardiac troponin I (cTnI), its relation to cardiomyopathy, and the contribution of the ACTN3 genotype to serum levels of cTnI in Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) remain unknown. In this study we aimed to reveal the characteristics of cTnI, assess whether cTnI is a biomarker for cardiomyopathy in these dystrophinopathies, and evaluate the contribution of the ACTN3 genotype to the serum levels of cTnI in DMD patients. Serum cTnI values obtained from 127 DMD and 47 BMD patients were analyzed retrospectively. The relationship between cTnI and echocardiography data or the ACTN3 XX genotype was assessed. The cTnI levels and proportion of patients with abnormal cTnI levels were significantly higher among DMD patients than BMD, especially in the second decade of life. In DMD, the cTnI level reached a maximum at 13 years, and left ventricular ejection fraction (LVEF) became abnormal approximately 1year subsequently. In BMD, the cTnI level peaked at the age of 14 years, and LVEF became abnormal 3 years later. Decreased LVEF was observed after cTnI elevation in both populations. cTnI levels by age in DMD patients with the ACTN3 XX genotype tended to increase significantly and early. Myocardial injury indicated by cTnI elevation was more common and severe in DMD patients. cTnI elevation preceding cardiac dysfunction may represent an early phase of cardiomyopathy progression and may be a biomarker for early detection of cardiomyopathy in these dystrophinopathies. The ACTN3 XX genotype may be a risk factor for early myocardial injury.

Association of serum cardiac troponin I and severity of coronary stenosis in patients with varied renal functions: a retrospective cohort study

Background and objectiveRecent studies showed cardiac troponin I (cTnI) might be a non-invasive biomarker to estimate the severity of coronary stenosis. However, serum cTnI is also found associated with renal...

Clemastine protects against sepsis-induced myocardial injury in vivo and in vitro

ABSTRACT Sepsis-induced myocardial dysfunction (SIMD) is associated with high morbidity and mortality rates; however, it lacks targeted therapies. Modulating cardiomyocyte autophagy maintains intracellular homeostasis during SIMD. Clemastine, a histamine receptor inhibitor, promotes autophagy and other effective biological functions. Nevertheless, the effect of clemastine on SIMD remains unclear. This study aimed to explore the underlying mechanism of clemastine in cardiomyocyte injury in cecum ligation and perforation (CLP)-induced rats and lipopolysaccharide (LPS)-stimulated H9c2 cells. Clemastine (10 mg/kg, 30 mg/kg, and 50 mg/kg) was intraperitoneally injected after 30 min of CLP surgery. Serum cTnI levels and the 7-day survival rate were evaluated. Echocardiograms and H&E staining were used to evaluate cardiac function and structure. TEM was used to detect the mitochondrial ultrastructure and autophagosomes. Clemastine significantly improved the survival rate and reduced cTnI production in serum. Clemastine ameliorated cellular apoptosis, improved mitochondrial ultrastructure both in vivo and in vitro, increased ATP content, decreased dynamin-related protein 1 (DRP1) expression, and decreased mitochondrial ROS levels. Additionally, clemastine treatment increased autophagosome concentration, LC3II/LC3I rate, and Beclin 1 expression. However, 3-methyladenine (3-MA), an autophagy inhibitor, could abolish the effect of clemastine on alleviating myocardial apoptosis. In conclusion, clemastine protected against cardiac structure destruction and function dysfunction, mitochondrial damage, apoptosis, and autophagy in vivo and in vitro. Moreover, clemastine attenuated myocardial apoptosis by promoting autophagy. This study provides a novel favorable perspective for SIMD therapy.

Effects of dexmedetomidine and its reversal with atipamezole on echocardiographic measurements and circulating cardiac biomarker concentrations in normal cats.

To investigate the effects of dexmedetomidine (DXM) and its subsequent reversal with atipamezole (APM) on the echocardiogram and circulating concentrations of cardiac biomarkers in cats. 14 healthy cats. Cats underwent echocardiography and measurements of circulating cTn-I and NT-proBNP concentrations before (PRE) and during (INTRA) DXM sedation (40 µg/kg IM) and 2 to 4 (2H POST) and 24 (24H POST) hours after reversal with APM. Administering DXM significantly decreased heart rate, right ventricular and left ventricular (LV) outflow tract velocities, and M-mode-derived LV free-wall thickness; increased LV end systolic diameter and volume; and caused valvar regurgitation. While sedative effects resolved within 25 minutes of APM reversal, the evolution of echocardiographic changes was mixed: LV ejection fraction and mitral valvar regurgitation score were different at 2H POST than at both INTRA and PRE (partial return toward baseline), LV end-diastolic volume was different PRE to INTRA and INTRA to 2H POST but not different PRE to 2H POST (full return toward baseline), and M-mode-derived LV free-wall thickness was significantly different from PRE to INTRA and PRE to 2H POST (no return toward baseline). Serum cTn-I and plasma NT-proBNP concentrations increased significantly with DXM, which remained significant 2H POST. Administration of DXM and APM reversal produced changes in echocardiographic results and in circulating cTn-I and NT-proBNP concentrations. Understanding these changes could help veterinarians differentiate drug effects from cardiac disease.

Cardiac Troponin I and Risk of Stroke: A Mendelian Randomization Study.

PurposeCardiac troponin I (cTnI) is a well-established biomarker for stroke prediction, especially in patients with heart diseases. However, the causal effect of circulating cTnI on stroke remains unclear.MethodsWe employed Mendelian Randomization (MR) analysis to determine the associations between genetically predicted circulating cTnI levels and stroke and its subtypes. Summary-level data for exposure and outcomes were generated from different genome-wide association studies. Single-nucleotide polymorphisms (SNPs) associated with circulating cTnI at genome-wide significance level (P < 5 × 10−8) were employed as instrumental variables (IVs). We used fixed-effect inverse-variance weighted (IVW) as the main method for pooling MR estimates. Sensitivity analyses and multivariable MR analyses were carried out to assess the robustness of the results.ResultsUsing the fixed-effects IVW method, we found that genetically elevated plasma cTnI levels may have a causal effect on the risk of cardioembolic stroke (CES) (odds ratio (OR), 1.58; 95% confidence interval (CI), 1.17–2.13; P = 0.003). Additional analyses including multiplicative random-effects (mre) IVW, weighted median, MR-Egger and MR-PRESSO yielded similar results, but with broader CIs that span 1.0. The total effect of cTnI on CES was attenuated by adjusting for the effect of atrial fibrillation (OR,1.26; 95% CI, 0.76–2.11; P = 0.371) and smoking (OR,1.53; 95% CI, 0.87–2.66; P = 0.137). In addition, we found no causal effect of cTnI on the risk of any stroke and other stroke subtypes, including any ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, and intracerebral hemorrhage. These results were consistent across sensitivity analyses.ConclusionThis study provides little evidence that increased serum cTnI levels lead to a higher risk of stroke.

Effect of early intervention on short-term prognosis of patients with myocardial injury induced by acute carbon monoxide poisoning.

AimThis study aimed to investigate the effect of early intervention on the short‐term prognosis of patients with myocardial injury induced by acute carbon monoxide poisoning (ACOP).Methods and resultsWe performed a retrospective cohort study of 139 patients admitted to the hospital for ACOP‐induced acute toxic cardiopathy. Compared with the mild and moderate toxic cardiopathy group, the severe toxic cardiopathy group has significantly increased coma time, acute physiology and chronic health status (APACHE) II score, and the length of hospital stay and significantly reduced proportion of patients with immediate endotracheal intubation and early admission to intensive care unit (ICU) (all P < 0.05). The cardiac troponin I (cTnI) levels and corrected QT dispersion (QTcd) duration in three patient groups were significantly higher (all P < 0.05) than those in the control group, with the highest in the severely toxic heart disease group. Serum cTnI level and QTcd duration were two independent predictors of myocardial injury in ACOP patients. There was a positive correlation between the APACHE II score and serum cTnI level/QTcd duration at admission. The sensitivities of cTnI and QTcd at admission to diagnose serious cardiovascular events were 78.6% and 85.7%, respectively, and the specificities were both 75%.ConclusionsAcute carbon monoxide poisoning patients with myocardial injury need to be admitted to the hospital as early as possible. For patients with severe hypoxia, an artificial airway should be established as early as possible, and patients should be admitted to the monitoring ward to stabilize their condition at the early stage of poisoning. Meanwhile, changes in QTcd, serum cTnI, and creatine kinase‐MB (CK‐MB) should be closely observed.

Positive Relationship of RDW with NT-proBNP and cTnI in Acute Myocardial Infarction Patients.

The goal of the study was to investigate the relationship of several parameters of complete blood count (CBC) with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in a cohort of acute myocardial infarction (AMI) patients. One hundred and one AMI patients were analyzed in this retrospective study. CBC, serum NT-proBNP, and cTnI levels were detected at the time of admission and on the day before or the day of discharge. The correlation between CBC with NT-proBNP and cTnI was analyzed. In this study, we found that red cell distribution width (RDW), red cell distribution width - coefficient of variation (RDW-CV), monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), NT-proBNP, and cTnI were significantly higher in AMI patients on the day of admission than the day before or the day of discharge. RDW and RDW-CV were significantly related with serum NT-proBNP and cTnI levels both at the time of admission and the day before or the day of discharge. RDW and RDW-CV were changed dramatically and synchronized with serum NT-proBNP and cTnI levels after the recovery. These results suggested that RDW and RDW-CV could be used as simple and convenient indicators to assess the condition of AMI patients.

Optimization of exercise preconditioning duration in protecting from exhausted exercise-induced cardiac injury in rats.

The effect of different duration of exercise preconditioning (EP) on protecting from exhaustive exercise-induced cardiac injury (EECI) has been optimized in rats. Male Sprague-Dawley rats were divided into six groups: the control group, exhaustive exercise (EE) group, EP 20-min + EE group, EP 40-min + EE group, EP 60-min + EE group and EP 80-min + EE group. The EP groups were subjected to treadmill running at the intensity of 74.0% V̇O2 max. Changes of exercise capacity, cardiac pathology, myocardial enzymology, electrocardiogram (ECG), cardiac function, and mitochondrial respiratory function were compared. Compared to the C group, the EE group has shown significant decrease of exercise capacity, elevation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTn-I) levels, cardiac morphology change, ECG disturbance, cardiac dysfunction and reduction of myocardial mitochondrial respiration function. Compared to the EE group, the EP groups have shown significant elevation of exercise capacity, decrease of serum NT-proBNP and cTn-I, improvement of cardiac function and myocardial mitochondrial electron transfer pathway complex I, II and IV activity. The correlation analyses showed protection of EP was proportional to EP duration from 20-min to 60-min. EE caused cardiac injury. EP could protect from EECI by alleviating myocardial damage, improving cardiac function and mitochondrial ETP complex I, II and IV activity. EP protection was positively correlated to EP duration from 20-min to 60-min with EP intensity fixed at 74.0% V̇O2 max.

Use of cardiac troponin I (cTnI) levels to diagnose severe hypoxia and myocardial injury induced by perinatal asphyxia in neonatal dogs

Prolonged perinatal asphyxia and subsequent severe hypoxia are the main causes of mortality in neonatal dogs in the first days of life. In medicine, specific cardiac biochemical markers, such as troponin I, are used to diagnose ischemic and nonischemic myocardial injury in asphyxiated newborns after birth. Thus, the objectives of this study were to compare the levels of cardiac troponin I (cTnI) between asphyxiated and nonasphyxiated newborn dogs and evaluate the correlations of cTnI levels with the modified Apgar score, the levels of oxygen saturation, blood glucose, and lactatemia, and blood gas parameters. This study aimed to determine the possible use of cTnI as a marker of severe hypoxia and myocardial ischemic injury in neonatal dogs. Fifteen animals in a eutocic vaginal delivery group (VG), 15 animals in a cesarean section group (CG), and 13 animals in a hypoxia (asphyxiated) group (HG) were evaluated. The animals in the asphyxiated group were from dystocic deliveries and born by vaginal delivery or cesarean section. All groups were evaluated at birth and after 60 min. The newborns in the VG and CG exhibited mixed acidosis (respiratory acidosis due to increased partial pressure of CO2 (pCO2) and metabolic acidosis due to reduced pH and bicarbonate (HCO3) levels, base excess/deficit in the extracellular fluid compartment (BEecf), and increased lactate levels) due to transient physiological hypoxemia at birth. The cTnI levels in the VG and CG were within the reference standards for healthy dogs. No correlations between cTnI level and the other parameters were observed in the VG and CG. Newborns in the HG exhibited prominent mixed acidosis (p < 0.05) due to severe hypoxemia. The Apgar score and blood gas parameters showed that these dogs were born asphyxiated, and they presented low vitality and the need for resuscitation maneuvers. The cTnI levels in the HG were significantly higher than those in the VG and CG (p < 0.05) and above the reference standards for healthy dogs, which indicated ischemic myocardial injury. The cTnI level was negatively correlated (p < 0.05) with the parameters Apgar score, heart rate, peripheral oxygen saturation (sO2) level, reflex score, and total carbon dioxide (TCO2) level and positively correlated (p < 0.01) with lactate level. This study showed that asphyxiated newborn dogs have higher serum cTnI levels than nonasphyxiated newborn dogs; thus, the cTnI can be used as a marker of severe hypoxia and ischemic myocardial damage in newborn dogs.

Evidence of myocardial injury in horses with colic

Development of endotoxemia associated with gastrointestinal injury is often observed in horses with colic. Such patients are likely to develop cardiovascular complications associated with endotoxemia, including myocardial injury. Few studies have investigated the prevalence of myocardial injury in horses with colic. Cardiac biomarkers such as cardiac troponin I (cTnI) have been extensively used in human and veterinary medicine for diagnosis of myocardial injury. The aim of the present study was to investigate the occurrence of myocardial injury in horses with colic by measuring serum cTnI concentrations. Myocardial tissue samples from non-surviving horses were also subjected to histopathological evaluation. Serum cTnI concentration was measured in 10 healthy horses and 39 horses with colic. Associations were determined of cTnI concentration, and variables such as health status (healthy and horses with colic), type of colic (inflammatory, impaction, and unknown), the severity of abdominal pain (mild, moderate and severe), and clinical outcome (survivor to discharge and non-survivor). As compared with healthy horses, cTnI concentrations were significantly elevated in horses with colic (P = 0.004). In horses with colic, an abnormal cTnI concentration was significantly associated with inflammatory colic (P&lt;0.05), severe abdominal pain (P&lt;0.01), and negative clinical outcome (P&lt;0.0001). Further, histopathological evaluation of the myocardial muscles revealed a varying degree of myocardial degeneration and necrosis. The present study suggested that horses with severe colic and increased cTnI levels are more likely to develop myocardial injury. Elevated levels of cTnI may also be indicative of poor prognosis in horses with severe colic.

Forensic significance of cTnI serum for the detection of terminal myocardial damage in rats (Rattus norvegicus) caused by hyperthermia

ObjectivesTo determine whether the biochemical marker cTnI with circulating value has forensic significance in the detection of myocardial damage in rats in experimental conditions of hyperthermia by exposure to water temperatures of 41 °C. Material and methodsThe study was conducted on 24 adult Wistar rats that were divided into two experimental groups, depending on water temperature exposure of 37 °C (KG, n = 8) and 41 °C (G41, n = 16). Depending on the length of time of exposure to water temperatures of 41 °C are further divided into G41-AM (20 min of exposure), G41-PM (exposure until death). Blood for analysis of the concentration of cardiac troponin I (cTnI) was taken before the experiment and after the expiration of the given duration of the experiment of 20 min or death. The concentration of cTnI was determined in serum by ELISA method. The level of statistical significance was, p < 0.05. ResultsEight rats of the G41 group achieved a core temperature that is the threshold for heat stroke. The median survival time for group G41 was 175.5 min. The median cTnI was 358.64 for group KG 37. The control group of rats had significantly lower serum cTnI values compared to G41. Examination of the length of exposure to appropriate temperatures led to significant increases in cTnI in the serum; A significant difference was found in the values of cTnI KG37 and G41-PM. CTnI values differed significantly in the G41-AM and G41-PM groups. In G 41 °C, a positive correlation was found between serum cTnI values and body temperature measured in fatal outcome. ConclusionsCTnI with their changes in serum concentration indicate exposure to high water temperature.

Early cardiopulmonary resuscitation on serum levels of myeloperoxidase, soluble ST2, and hypersensitive C-reactive protein in acute myocardial infarction patients.

BACKGROUNDPrompt and effective cardiopulmonary resuscitation (CPR) can promote the recovery of spontaneous circulation to some extent and can save patients’ lives. The minimum target of cardiac resuscitation is the restoration of spontaneous circulation (ROSC). However, owing to prolonged sudden cardiac arrest, there is relatively high mortality within 24 h after cardiac resuscitation. Moreover, severe cerebral anoxia can deteriorate the prognosis of patients. Therefore, it is important to adopt an effective clinical evaluation of acute myocardial infarct (AMI) patients’ prognosis after cardiac resuscitation for the purpose of prevention and management.AIMTo investigate early CPR effects on human myeloperoxidase (MPO), soluble ST2 (sST2), and hypersensitive C-reactive protein (hs-CRP) levels in AMI patients.METHODSIn total, 54 patients with cardiac arrest caused by AMI in our hospital were selected as the observation group, and 50 other patients with AMI were selected as the control group. The differences in serum levels of MPO, sST2, and hs-CRP between the observation group and the control group were tested, and the differences in the serum levels of MPO, sST2, and hs-CRP in ROSC and non-ROSC patients, and in patients who died and in those who survived, were analyzed.RESULTSSerum levels of MPO, sST2, hs-CRP, lactic acid, creatine kinase isoenzyme (CK-MB), and cardiac troponin I (cTnI) were significantly higher in the observation group than in the control group (P < 0.05). Serum levels of MPO, sST2, hs-CRP, lactic acid, CK-MB, and cTnI in the observation group were lower after CPR than before CPR (P < 0.05). In the observation group, MPO, sST2, hs-CRP, lactic acid, CK-MB, and cTnI serum levels were lower in ROSC patients than in non-ROSC patients (P < 0.05). MPO, sST2, hs-CRP, and lactic acid serum levels of patients who died in the observation group were higher than those of patients who survived (P < 0.05). The areas under receiver operating characteristic curve predicted by MPO, sST2, hs-CRP, lactic acid, CK-MB, and cTnI were 0.616, 0.681, 0.705, 0.704, 0.702, and 0.656, respectively (P < 0.05). The areas under receiver operating characteristic curve for MPO, SST2, hs-CRP, and lactic acid to predict death were 0.724, 0.800, 0.689, and 0.691, respectively (P < 0.05). Logistic regression analysis showed that MPO, sST2, and hs-CRP were the influencing factors of ROSC [odds ratios = 1.667, 1.589, and 1.409, P < 0.05], while MPO, sST2, hs-CRP, and lactic acid were the influencing factors of death (odds ratios = 1.624, 1.525, 1.451, and 1.365, P < 0.05).CONCLUSIONSerum levels of MPO, sST2, hs-CRP, and lactic acid have a certain value in predicting recovery and prognosis of patients with ROSC.

Protective role of emodin in rats with post-myocardial infarction heart failure and influence on extracellular signal-regulated kinase pathway

ABSTRACT We aimed to explore the effects of emodin on the energy metabolism of myocardial cells in rats with post-myocardial infarction (MI) heart failure (HF) and the extracellular signal-regulated kinase (ERK) pathway. The model of MI was established by ligation of the left anterior descending branch. After 4 weeks, the rats with left ventricular ejection fraction (LVEF) of ≤45% were used aspost-MI HF model animals and randomly divided into model, low-dose, middle-dose, high-dose and control groups (n=10). Low-, middle- and high-dose groups were gavaged with 20 mg/kg, 40 mg/kg and 60 mg/kg emodin daily, respectively. After administration for 14 d, the changes in LVEF, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD) and interventricular septum thickness (IVS) were analyzed. The apoptosis rate of myocardial cells was detected by TUNEL staining. The levels of serum cardiac troponin I (cTnI) and peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) were determined using ELISA, and the expressions of mitochondrial respiratory chain complex I protein and phosphorylated-ERK (p-ERK) in myocardial tissues were determined by Western blotting. Compared with model group, LVEDD, LVESD, apoptosis rate of myocardial cells, levels of serum cTnI and PGC-1, and expressions of complex I and p-ERK in myocardial tissues significantly decreased, while LVEF and IVS increased in low-dose, middle-dose, high-dose and control groups (P<0.05). The changes in the above indices were significantly dependent on the dose of emodin (P<0.05).Emodin can significantly relieve post-MI HF, reduce the apoptosis rate of myocardial tissues, and ameliorate the cardiac function of rats.

Iguratimod Alleviates Myocardial Ischemia/Reperfusion Injury Through Inhibiting Inflammatory Response Induced by Cardiac Fibroblast Pyroptosis via COX2/NLRP3 Signaling Pathway.

Background: NLRP3 inflammasome contributes a lot to sterile inflammatory response and pyroptosis in ischemia/reperfusion (I/R) injury. Cardiac fibroblasts (CFs) are regarded as semi-professional inflammatory cells and they exert an immunomodulatory role in heart. Iguratimod provides a protective role in several human diseases through exerting a powerful anti-inflammatory effect. However, it is still unclear whether iguratimod could alleviate myocardial I/R injury and whether inflammation triggered by NLRP3-related pyroptosis of CFs is involved in this process.Methods: Transcriptomics analysis for GSE160516 dataset was conducted to explore the biological function of differentially expressed genes during myocardial I/R. In vivo, mice underwent ligation of left anterior descending coronary artery for 30 min followed by 24 h reperfusion. In vitro, primary CFs were subjected to hypoxia for 1 h followed by reoxygenation for 3 h (H/R). Iguratimod was used prior to I/R or H/R. Myocardial infarct area, serum level of cardiac troponin I (cTnI), pathology of myocardial tissue, cell viability, lactate dehydrogenase (LDH) release, and the expression levels of mRNA and protein for pyroptosis-related molecules were measured. Immunofluorescence was applied to determine the cellular localization of NLRP3 protein in cardiac tissue.Results: During myocardial I/R, inflammatory response was found to be the most significantly enriched biological process, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling was a crucial pathway in mediating cardiac inflammation. In our experiments, pretreatment with iguratimod significantly ameliorated I/R-induced myocardial injury and H/R-induced pyroptosis of CFs, as evidenced by reduced myocardial infarct area, serum cTnI level, and LDH release in supernatants, as well as improved pathology of cardiac tissue and cell viability. Immunofluorescence analysis showed that NLRP3 was mainly localized in CFs. Moreover, iguratimod inhibited the expression of pro-inflammatory cytokines and pyroptosis-related molecules, including NLRP3, cleaved caspase-1, and GSDMD-N.Conclusion: Our results suggested that inflammatory response mediated by NOD-like receptor signaling is of vital importance in myocardial I/R injury. Iguratimod protected cardiomyocytes through reducing the cascade of inflammation in heart by inhibiting cardiac fibroblast pyroptosis via the COX2/NLRP3 signaling pathway.

Development of a novel ssDNA aptamer targeting cardiac troponin I and its clinical applications.

Cardiac troponin I (cTnI) is a specific biomarker of acute myocardial infarction (AMI). However, cTnI detection kits prepared with antibodies have many defects. Nucleic acid aptamers are sequences of single-strand DNA or RNA that can overcome the deficiency of antibodies. Herein, sandwich ELONA methods were established based on aptamers. Two selected ssDNA aptamers (Apt3 and Apt6) showed high binding affinity and sensibility (Apt3: Kd = 1.01 ± 0.07nM, Apt6: k = 0.68 ± 0.05) and did not bind to the same domain of cTnI. Therefore, these two aptamers can be applied to the ELONA methods. The detection range of cTnI using the dual-aptamer sandwich ELONA method was 0.05-200ng/mL, and the bioanalytical method verification results can meet the national standard of Chinese Pharmacopoeia (2020 Edition). There was no difference between results of the dual-aptamer sandwich ELONA method and the diagnostic results of serum obtained from 243 people (P = 0.39, P ˃ 0.05). The sensitivity and specificity of the ELONA with cTnI in serum were 96.46% and 93.85%, respectively. Compared with the FICA kit, which is clinically used, the consequences of ELONA method are closer to the diagnostic results. This study suggests that the aptamers Apt3 and Apt6 have high affinity and strong specificity and that the dual-aptamer sandwich ELONA method has a wide detection range and can be used to determine cTnI in serum, with potential applications in the diagnosis of AMIs.

A Study of The Cardio-Protective Effect of Pioglitazone on Isoprenaline- Induced Myocardial Infarction in Male Albino Rats

ABSTRACT Background: Isoprenaline (ISO) in large doses induces morphological and functional alterations in the heart leading to myocardial necrosis. It also produces excessive free radicals resulting from oxidative metabolism of catecholamine. There are increasing evidences that cardiotoxicity of ISO occurs because of generation of free radicals and oxidative stress. Objective: To investigate the protective effect of pioglitazone on the outcome of isoprenaline (ISO) induced myocardial infarct-like lesions in rats. Materials and methods: 50 male Wistar albino rats (150-200gm) were selected for this study. The rats were divided into five groups each consisted of 10 rats. This study was conducted at Department of Pharmacology, Faculty of Medicine, Al-Azhar University (Assiut). Results: Results showed that pretreatment with pioglitazone significantly decreased the activity of LDH, CK, TNF alpha, IL 6 and the levels of CTnI in serum of ISO-induced rats. Our results showed that pretreatment with pioglitazone significantly (p < 0.01) decreased the level of MDA compared with ISO alone-induced rats. Conclusion: Pioglitazone has a valuable protective role against myocardial infarction through its action as peroxisome proliferator activated receptor gamma (PPAR-γ) agonist.

Diagnostic value and significance of serum miR-132 combined with miR-223 for sepsis-induced cardiomyopathy.

In previous studies, miR-132 and miR-223 were considered to be involved in cellular and pathological processes of diseases. However, the role of early diagnosis and prognosis evaluation in sepsis-induced cardiomyopathy (SIC) remains unknown. The present study aimed to explore the diagnostic value of combined detection of miR-132 and miR-223 for SIC and their correlation with creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor α (TNF-α), and interleukin-6 (IL)-6. SIC patients (n=80) admitted to Tianjin Medical University General Hospital were assigned to the research group (RG), while 60 healthy participants receiving physical examinations at the same period were assigned to the control group (CG). Serum expression profiles of miR-132 and miR-223 were detected by the RT-qPCR. CK-MB and cTnI were assessed using chemiluminescence assay, and TNF-α and IL-6 by enzyme-linked immunosorbent assay (ELISA). Serum miR-132 and miR-223 levels were significantly lower in the RG than in the CG (P<0.001). The sensitivity and specificity for the diagnosis of SIC were 82.50 and 71.67% for miR-132, 95.00 and 61.67% for miR-223, as well as 86.25 and 86.67% for miR-132 combined with miR-223. Serum miR-132 and miR-223 levels were significantly higher in the survivor group than in the deceased group (P<0.001). The sensitivity and specificity for the prognosis of SIC were 85.96 and 65.22% for miR-132 combined with miR-223. Serum miR-132 and miR-223 were negatively correlated with serum CK-MB, cTnI, TNF-α, and IL-6 (P<0.001). miR-132 combined with miR-223 can be used for early diagnosis and prognostic evaluation of SIC, and the two are correlated with CK-MB, cTnI, TNF-α, and IL-6.