Serum Levels Of Cardiac Troponin Research Articles

Traditional vs. modified Ringer lactate-based del Nido cardioplegia impacts on clinical outcomes in patients undergoing coronary artery bypass grafting: results from a clinical trial

Introduction: myocardial protection with cardioplegia solution is one of the precautions during coronary bypass grafting surgery (CABG) with cardiopulmonary bypass (CPB) to reduce myocardial damage and ischemia/reperfusion injuries. Unfortunately, the major component of the del Nido cardioplegia solution, Plasma-Lyte A, is unreachable in Iran due to high cost. Therefore, we have utilized lactate Ringer's solution as the base solution for our modified del Nido solution (LR DN). Study design and methods: the present clinical trial was performed on 18-75 year old patients (EF>35%) undergoing CABG with CPB in Imam Hossein hospital Tehran-Iran in 2021. Patients were randomly allocated to LR DN (modified del Nido cardioplegia) and PL DN (standard del Nido cardioplegia solution) groups. Serum level of cardiac troponin I (cTnI) at baseline, declamp, ICU admission, and 24 hours after admission, the type and dosage of inotrope agents, EF, rate of arrhythmia after clamp removal and lactate level were measured and compared between groups. Results: 109 patients were recruited. There were no statistically significant differences between the PL DN cardioplegia and LR DN groups for cardiopulmonary bypass times, cardiac enzymes, transfusion requirements, and arterial blood gases. However, postoperative serum levels of cTnI among patients in the LR DN group was significantly higher than patients of the PL DN group after ICU admission and 24 hours postoperatively. Also, more patients needed epinephrine administration in the operating room in the LR DN group (29.8% vs. 11.5%; p: 0.019 vs. PL DN group). Conclusion: we concluded that standard del Nido cardioplegia solution offers better myocardial protection compared with Ringer's lactate-based del Nido cardioplegia in adult patients undergoing CABG with CPB. We recommend using standard del Nido cardioplegia with a base of Plasma-Lyte A for patients presenting for CABG surgery.

Characterization of clinical serum cardiac biomarker levels in individuals with Friedreich ataxia

Friedreich ataxia is a progressive autosomal recessive neurodegenerative disorder characterized by ataxia, dyscoordination, and cardiomyopathy. A subset of patients with Friedreich ataxia have elevated levels of serum cardiac troponin I, but associations with disease outcomes and features of cardiomyopathy remain unclear. In this study, we characterized clinically obtained serum cardiac biomarker levels including troponin I, troponin T, and B-type natriuretic peptide in subjects with Friedreich ataxia and evaluated their association with markers of disease. While unprovoked troponin I levels were elevated in 36% of the cohort, cTnI levels associated with a cardiac event (provoked) were higher than unprovoked levels. In multivariate linear regression models, younger age predicted increased troponin I values, and in logistic regression models younger age, female sex, and marginally longer GAA repeat length predicted abnormal troponin I levels. In subjects with multiple assessments, mean unprovoked troponin I levels decreased slightly over time. The presence of abnormal troponin I values and their levels were predicted by echocardiographic measures of hypertrophy. In addition, troponin I levels predicted long-term markers of clinical cardiac dysfunction over time to a modest degree. Consequently, troponin I values provide a marker of hypertrophy but only a minimally predictive biomarker for later cardiac manifestations of disease such as systolic dysfunction or arrhythmia.

Daunorubicin Treatment Impairs Cardiac Function in The Ts65Dn Mouse Model Of Down Syndrome

Anthracycline treatment for leukemia is effective but has toxic side effects on the cardiovascular system. Few studies regarding the impact of anthracyclines on the heart in individuals with Down syndrome have been addressed although they are at a higher risk of developing leukemia. It is unknown if established mechanisms apply to individuals with Down syndrome. We hypothesize that anthracycline cardiotoxicity will lead to the enhanced impairment of cardiac function and initiate pronounced vascular dysfunction in a mouse model of Down syndrome. We used the Ts65Dn mouse model of Down syndrome to investigate the impact of daunorubicin chemotherapy on survival, arterial stiffness and left ventricular function. Four-month-old Ts65Dn (n=12) and wild-type control Ts65Dn (WT, n=8) mice were treated with 2mg/kg of daunorubicin or saline. Following treatment, left ventricular catheterization was performed to assess cardiac function. Serum cardiac troponin levels were evaluated using ELISA. Histological analysis was conducted on the heart and aorta of mice to assess the accumulation of elastin and collagen. We found decreased end-diastolic pressure (p=0.016) and ejection fraction (p=0.029) in Ts65Dn daunorubicin-treated mice compared to WT control. However, contractility (end-systolic pressure-volume relationship, p=0.221) and diastolic stiffness coeffcient (end-diastolic pressure-volume relationship, p=0.418) remained unchanged. Ts65Dn mice had a higher cardiac troponin concentration (p=0.02). Histological assessment showed no significant difference in collagen (p=0.841) and elastin (p=0.768) content. Daunorubicin negatively impacted end-diastolic pressure and ejection fraction of the Ts65Dn mouse model of Down syndrome. We demonstrated that we could recapitulate the findings of anthracycline cardiotoxicity in Ts65Dn mice indicating this is a good model to investigate toxicity. Continued work with this model will better elucidate the mechanisms underlying anthracycline cardiotoxicity in Down syndrome. This shows the need for constant screening after anthracycline treatment which will improve the survival of this population. NIH R21 HD099573. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The negative effects of statin drugs on cardiomyocytes: current review of laboratory and experimental data (mini-review).

Statin drugs have long been used as a key component of lipid-lowering therapy, which is necessary for the prevention and treatment of atherosclerosis and cardiovascular diseases. Many studies focus on finding and refining new effects of statin drugs. In addition to the main lipid-lowering effect (blocking cholesterol synthesis), statin drugs have a number of pleiotropic effects, including negative effects. The main beneficial effects of statin drugs on the components of the cardiovascular system are: anti-ischemic, antithrombotic, anti-apoptotic, antioxidant, endothelioprotective, anti-inflammatory properties, and a number of other beneficial effects. Due to these effects, statin drugs are considered one of the main therapeutic agents for the management of patients with cardiovascular pathologies. To date, many review manuscripts have been published on the myotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity and diabetogenic effects of statins. However, there are no review manuscripts considering the negative effect of statin drugs on myocardial contractile cells (cardiomyocytes). The purpose of this review is to discuss the negative effects of statin drugs on cardiomyocytes. Special attention is paid to the cardiotoxic action of statin drugs on cardiomyocytes and the mechanisms of increased serum levels of cardiac troponins. In the process of preparing this review, a detailed analysis of laboratory and experimental data devoted to the study of the negative effects of statin drugs on cardiomyocytes was carried out. The literature search was carried out with the keywords: statin drugs, negative effects, mechanisms, cardiac troponins, oxidative stress, apoptosis. Thus, statin drugs can have a number of negative effects on cardiomyocytes, in particular, increased oxidative stress, endoplasmic reticulum stress, damage to mitochondria and intercalated discs, and inhibition of glucose transport into cardiomyocytes. Additional studies are needed to confirm and clarify the mechanisms and clinical consequences of the negative effects of statin drugs on cardiomyocytes.

Lead activates neutrophil degranulation to induce early myocardial injury in mice

Lead (Pb) is a pervasive toxic metal contaminant associated with a high risk of myocardial injury. However, the precise mechanism underlying Pb-induced myocardial injury has yet to be fully elucidated. In this study, a murine model of Pb exposure (0, 1, 5, and 10 mg/kg) was employed to investigate the involvement of neutrophil degranulation in the induction of myocardial injury. Notably, serum levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) increased significantly in Pb-exposed mice, whereas cTnI levels in cardiomyocytes decreased, suggesting that Pb exposure may cause early myocardial injury. Moreover, Pb exposure was found to promote neutrophil degranulation, as evidenced by elevated myeloperoxidase (MPO) and neutrophil elastase (NE) concentrations in both the serum of Pb-exposed workers and Pb-exposed mice, as well as the extracellular supernatant of neutrophils following exposure. However, we found that serum level of cTnI enhanced by Pb exposure is associated with increased NE levels in the serum, but not with MPO levels. Upon treatment with NE inhibitor (sivelestat), the serum level of cTnI markedly reduced in Pb-exposed mice, we found that early myocardial injury is associated with NE levels in the serum. At the molecular level, western blotting analysis revealed an upregulation of ERK1/2 expression in vitro following Pb exposure, suggesting that the activation of the ERK1/2 signaling pathway may underlie the participation of neutrophil degranulation in Pb-induced myocardial injury. In summary, our findings demonstrate that Pb exposure can initiate early myocardial injury by promoting the neutrophil degranulation process, thereby highlighting the potential role of this process in the pathogenesis of Pb-associated myocardial injury.

Study on the Specific Expression of Infrared Radiation Temperature on the Body Surface of Acupoint in Rats with Chronic Myocardial Ischemic Injury.

Infrared thermal imaging technology was used to observe the changes in infrared radiation temperature at acupoints in rats caused by chronic myocardial ischemia injury. This study aims to compare the difference of body surface infrared radiation temperature information of three groups of acupoints: bilateral Neiguan (PC6), bilateral Yanglingquan (GB33), and bilateral Sham Acupoints (SA) in the pathological state of myocardial ischemia injury, and to explore the relationship between acupoints and viscera state. SPF adult Wistar male rats (n = 20) were randomly divided into a control (CTL; n = 10) and an isoproterenol group (ISO; n = 10). Chronic myocardial injury was induced in rats by subcutaneous injection of isoproterenol hydrochloride for 14 d. On the second day after the establishment of the model, the serum levels of cardiac troponin (cTnI) and creatine kinase isoenzyme (CK-MB) were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of the myocardial tissue in the two groups were observed by hematoxylin-eosin (HE) staining and their pathological scores were evaluated, which was then used to determine the myocardial ischemic injury. Two days before and after the establishment of the model, the electrocardiograms (ECG) of the two groups of rats were recorded by the (ECG) data acquisition system, and the infrared thermal imaging platform was used to detect the temperature of the six acupoints. 1. After subcutaneous injection of isoproterenol hydrochloride for 14 days, the ST segment of the ECG decreased in the ISO group compared with that of the CTL group; 2. Myocardial tissue injury was serious in the ISO group compared to the CTL group; 3. Serum cTn-I and CK-MB were significantly increased (P <0 01) in the ISO group, compared to that in the CTL group; 4. The infrared radiation temperature on the body surface of bilateral Neiguan (PC6) acupoints decreased significantly in the ISO group, compared to that of the CTL group. Infrared thermal imaging technology can be used to detect the changes in the energy state of acupoints. Chronic myocardial ischemic injury can cause a decrease in IR temperature on the body surface of bilateral Neiguan (PC6) acupoints, suggesting that visceral diseases can lead to changes in the energy metabolism of acupoints.

Evaluation of cardiopreventive effects of Ximenia americana (Linn.) and Pappea capensis (Eckl. and Zeyh.) leaf aqueous extracts in rat models with myocardial infarction

BackgroundMyocardial infarction is a significant health issue in both wealthy and underdeveloped nations. Globally, it is the leading cause of deaths among cardiovascular diseases. In 2012, myocardial infarction-related deaths were about 14.1 million out of 17.5 million cardiovascular disease-related deaths. Clinical management of myocardial infarction remains a challenge because most conventional drugs provide symptomatic relief only. In addition, conventional remedies are associated with numerous advese effects and arguably, in many cases are quite expensive. Hence, herbal remedies, which are widely available, with comparatively fewer side effects, and are affordable, provide a more attractive therapeutic alternative. This study aimed at determining cardiopreventive effects of aqueous leaf extracts of X. americana and P. capensis. Phytochemical screening was done using liquid chromatography-mass spectrometry. Wistar albino rats were employed to test for cardiopreventive effects of the extracts and were randomized into 6 groups of 5 animals each. Groups I, II, and III were normal, negative, and positive controls, respectively, and rats were given normal saline, salbutamol (7.5 mg/Kg bw), and propranolol, respectively. Groups IV, V, and VI rats were treated with extracts dose levels 50, 100, and 150 mg/Kg bw, respectively. Biochemical analysis was done to determine effects of the extracts on levels of serum cardiac troponin T, creatine kinase-MB, lactate dehydrogenase-1, and lipid profiles. Levels of oxidative stress markers were determined in the heart tissue.ResultsThe LC–MS analysis revealed different phytocompounds in the extracts, including flavonoids, phenolic acids, glycosides and tannins, which are known to confer cardioprotective activities. The extracts significantly prevented increase in cardiac troponin T, creatine kinase-MB, lactate dehydrogenase-1, total cholesterol, triglycerides, LDL, and MDA levels, as well as a significant increase in superoxide dismutase, catalase, glutathione peroxidase, and HDL levels.ConclusionsThis study confirmed that Ximenia americana and Pappea capensis extracts have the potential to prevent myocardial infarction in rats. Generally, P. capensis extract showed better activity as compared to X. americana extract. The effects of the extracts could be attributable to the presence of various cardioactive phytocompounds. Therefore, these plants can be considered in the development of potent and safe cardiopreventive drugs.

Cell-Specific Mechanisms in the Heart of COVID-19 Patients.

From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation, the greater the COVID-19 illness severity and in-hospital death risk. Whether these consequences were due to direct SARS-CoV-2 infection of cardiac cells or secondary to inflammatory responses steered early cardiac autopsy studies. SARS-CoV-2 was reportedly detected in endothelial cells, cardiac myocytes, and within the extracellular space. However, findings were inconsistent and different methodologies had their limitations. Initial autopsy reports suggested that SARS-CoV-2 myocarditis was common, setting off studies to find and phenotype inflammatory infiltrates in the heart. Nonetheless, subsequent studies rarely detected myocarditis. Microthrombi, cardiomyocyte necrosis, and inflammatory infiltrates without cardiomyocyte damage were much more common. In vitro and ex vivo experimental platforms have assessed the cellular tropism of SARS-CoV-2 and elucidated mechanisms of viral entry into and replication within cardiac cells. Data point to pericytes as the primary target of SARS-CoV-2 in the heart. Infection of pericytes can account for the observed pericyte and endothelial cell death, innate immune response, and immunothrombosis commonly observed in COVID-19 hearts. These processes are bidirectional and synergistic, rendering a definitive order of events elusive. Single-cell/nucleus analyses of COVID-19 myocardial tissue and isolated cardiac cells have provided granular data about the cellular composition and cell type-specific transcriptomic signatures of COVID-19 and microthrombi-positive COVID-19 hearts. Still, much remains unknown and more in vivo studies are needed. This review seeks to provide an overview of the current understanding of COVID-19 cardiac pathophysiology. Cell type-specific mechanisms and the studies that provided such insights will be highlighted. Given the unprecedented pace of COVID-19 research, more mechanistic details are sure to emerge since the writing of this review. Importantly, our current knowledge offers significant clues about the cardiac pathophysiology of long COVID-19, the increased postrecovery risk of cardiac events, and thus, the future landscape of cardiovascular disease.

High Serum Levels of Cardiac Troponin I., Tumor Necrosis Factor-Α and D-Dimer Could be Used as Early Predictors for Upcoming Preeclampsia and its Severity

High Serum Levels of Cardiac Troponin I., Tumor Necrosis Factor-Α and D-Dimer Could be Used as Early Predictors for Upcoming Preeclampsia and its Severity

Androgen-deprivation therapy with leuprolide increases abdominal adiposity without causing cardiac dysfunction in middle-aged male mice: effect of sildenafil.

Androgen-deprivation therapy (ADT) is the primary systemic therapy for treating advanced or metastatic prostate cancer (PCa), which has improved survival outcomes in patients with PCa. However, ADT may develop metabolic and cardiovascular adverse events that impact the quality of life and lifespan in PCa survivors. The present study was designed to establish a murine model of ADT with a gonadotropin-releasing hormone (GnRH) agonist leuprolide and to investigate its effects on metabolism and cardiac function. We also examined the potential cardioprotective role of sildenafil (inhibitor of phosphodiesterase 5) under chronic ADT. Middle-aged male C57BL/6J mice received a 12-wk subcutaneous infusion via osmotic minipumps containing either saline or 18 mg/4 wk leuprolide with or without 1.3 mg/4 wk sildenafil cotreatment. Compared with saline controls, leuprolide treatment significantly reduced prostate weight and serum testosterone levels, confirming chemical castration in these mice. The ADT-induced chemical castration was not affected by sildenafil. Leuprolide significantly increased the weight of abdominal fat after 12-wk treatment without a change in total body weight, and sildenafil did not block the proadipogenic effect of leuprolide. No signs of left ventricular systolic and diastolic dysfunction were observed throughout the leuprolide treatment period. Interestingly, leuprolide treatment significantly elevated serum levels of cardiac troponin I (cTn-I), a biomarker of cardiac injury, and sildenafil did not abolish this effect. We conclude that long-term ADT with leuprolide increases abdominal adiposity and cardiac injury biomarker without cardiac contractile dysfunction. Sildenafil did not prevent ADT-associated adverse changes.

Role of the heat shock protein family in chlorpromazine-induced cardiotoxicity.

Chlorpromazine (CPZ), a first-generation antipsychotic, is widely used in treating schizophrenia and other psychiatric disorders. However, CPZ is also associated with an increased likelihood of sudden cardiac death, and the underlying mechanisms remain unclear. In our study, we aimed to determine the CPZ-induced changes in some members of the heat shock protein family in rat hearts and further explore the possible mechanisms of CPZ-induced cardiotoxicity. Twenty-four Sprague Dawley rats were randomly divided into three groups (n = 8 per group): control, low dose (33.216 mg/kg) and high dose (94.211 mg/kg). CPZ administration induced hypothermia in rats. Pathological changes, including ischaemia and hypoxia, were observed in rat hearts. Furthermore, the serum levels of cardiac Troponin T (c-TN-T) and brain natriuretic peptide (BNP) were elevated in the CPZ-exposed groups. Meanwhile, the protein and gene expression of HSP70, HSP60, HSP27 and HSP10 significantly differed between the CPZ-exposed and control groups. We conclude that acute CPZ exposure could lead to myocardial injury in rats, in which HSPs might play a crucial role. Further investigations are required to elucidate the underlying mechanisms.

Effects of Long-Term Endurance Exercise on Cardiac Morphology, Function, and Injury Indicators among Amateur Marathon Runners.

The purpose of this study was to investigate the effects of long-term endurance exercise on cardiac morphology and function, as well as injury indicators, among amateur marathon runners. We recruited 33 amateur runners who participated in a marathon. Participants were divided into experimental and control groups according to their National Athletic Grade. The experimental group included participants with a National Athletic Grade of 2 or better, and the control group included participants who did not have a National Athletic Grade. Cardiac morphology, function, and injury indicators were assessed before and after the participants' involvement in the Changsha International Marathon. All cardiac morphology and function indicators returned to pre-race levels at 24 h post-race, and left ventricular end-diastolic volume and left ventricular end-systolic volume indicators showed similar trends. Both stroke volume (SV) and percent fractional shortening (%FS) indicators showed similar trends in changes in the measurements before and after the race. SV showed no change between the pre-race and post-race periods. On the other hand, %FS showed a significant increase in the immediate post-race period, followed by restoration of its level at 24 h post-race. Among myocardial injury indicators, serum levels of cardiac troponin I, creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and N-terminal pro-b-type natriuretic peptide (NT-proBNP) measured before the race, immediately after the race, and 24 h after the race displayed similar trends in changes among CK, CK-MB, LDH, and AST, while NT-proBNP levels did not change. We concluded that high-level amateur marathon runners had greater heart volumes, as well as wall and septal thicknesses, than low-level marathon runners, with differences in heart volume being the most pronounced. Long-term high-intensity endurance exercise caused some damage to the hearts of amateur runners. High-level runners showed better myocardial repair ability, and their levels of myocardial injury markers showed greater decreases at 24 h post-race, while low-level runners had poorer myocardial repair ability.

Gender Specificities of Cardiac Troponin Serum Levels: From Formation Mechanisms to the Diagnostic Role in Case of Acute Coronary Syndrome

Cardiac troponins T and I are the main (most sensitive and specific) laboratory indicators of myocardial cell damage. A combination of laboratory signs of myocardial cell damage (elevated levels of cardiac troponins T and I) with clinical (severe chest pain spreading to the left side of the human body) and functional (rise or depression of the ST segment, negative T wave or emergence of the Q wave according to electrocardiography and/or decrease in the contractility of myocardial areas exposed to ischemia according to echocardiography) signs of myocardial ischemia is indicative of the ischemic damage to cardiomyocytes, which is characteristic of the development of acute coronary syndrome (ACS). Today, with early diagnostic algorithms for ACS, doctors rely on the threshold levels of cardiac troponins (99th percentile) and on the dynamic changes in the serum levels over several hours (one, two, or three) from the moment of admission to the emergency department. That said, some recently approved highly sensitive methods for determining troponins T and I show variations in 99th percentile reference levels, depending on gender. To date, there are conflicting data on the role of gender specificities in the serum levels of cardiac troponins T and I in the diagnostics of ACS, and the specific mechanisms for the formation of gender differences in the serum levels of cardiac troponins T and I are unknown. The purpose of this article is to analyze the role of gender specificities in cardiac troponins T and I in the diagnostics of ACS, and to suggest the most likely mechanisms for the formation of differences in the serum levels of cardiac troponins in men and women.

Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity

Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1β (IL-1β) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function.

43 CARDIAC TROPONINS AND COVID-19: WHAT DO WE KNOW ABOUT HETEROPHILIC ANTIBODIES?

Abstract Background During the Coronavirus disease-19 (COVID-19) pandemic, a significant increase in cardiovascular events and death for acute Myocardial Infarction (AMI) has been widely described. In turn, cardiac troponins represent the main serum diagnostic biomarkers of AMI. However, several mechanisms of troponins elevation other than AMI could be identified such as the analytic interference due to the Heterophilic Antibodies (HA), which represents a less explored and underestimated cause. Methods The research of the following keywords “Heterophilic” or “Heterophile Antibodies” associated with “Troponin”, “Troponin I”, “Troponin T” or “High-sensitive Troponin” have identified 73 works in the most popular bibliographic databases such as PubMed, Scopus, and Web of Science, in which the first was published in 1998. In our systematic review, the inclusion criteria have considered all the works in which clinical information about the patients are described. The results have included 55 papers for an overall population of 128 cases that have presented HA's interference in troponins’ assay. In the great part of the works, HA's capture test has been performed to diagnose this interference. The association between HA and COVID-19 has also been explored with the identification of three works in scientific literature. In addition, we reported a clinical case of a young patient with persistent high serum ultra-sensitive Troponin levels due to HA, during the COVID-19 pandemic. Results The results have indicated the most at-risk population in patients with a history of multiple hospitalizations and with poor cardiovascular risk factors, who usually complained of atypical chest pain combined with persistent elevation of cardiac troponins without high CK-MB values. Instead, only a few data could be isolated in the literature about HA's interference on troponins essay in COVID-19 patients. However, has been widely ascertained how increased serum levels of cardiac troponins have been identified in most of the SARS-COV-2 swabs positive populations, and several cardiac and extracardiac mechanisms may explain this condition. Conclusions The description of the most common clinical features of patients with HA's interference could help clinicians to early recognize this phenomenon, reducing the number of instrumental examinations and the hospitalization period of these patients. Therefore, the analytical mistake due to HA could be always considered in AMI differential diagnosis, and the use of HA's capture test in the at-risk population may determine an early diagnosis. Finally, the HA's phenomenon could increase during the COVID-19 period, considering how infections and vaccinations may stimulate heterophile's activity.

Hezi inhibits Tiebangchui-induced cardiotoxicity and preserves its anti-rheumatoid arthritis effects by regulating the pharmacokinetics of aconitine and deoxyaconitine

Ethnopharmacological relevanceTiebangchui (TBC, dried roots of Aconitum pendulum Busch. and Aconitum flavum Hand.-Mazz.) is a well-known Tibetan medicine for dispelling cold and relieving pain. In China, it is widely used in prevention and treatment of various diseases, such as rheumatoid arthritis (RA), traumatic injury, and fracture. However, its cardiotoxicity and neurotoxicity seriously restrict its clinical application. Traditionally, Hezi (HZ, dry ripe fruit of Terminalia chebula Retz. and Terminalia chebula Retz. var. tomentella Kurt.) is generally used in combination with TBC for the purpose of toxicity reducing and efficacy enhancing, but so far we still can’t clearly elucidate the compatibility effect and mechanism of the classical herbal pair. Aim of studyTo investigate the compatibility effect and mechanism of TBC co-administered with HZ. MethodsIn the present study, we clarified the cardioprotective role of HZ on the cardiotoxicity induced by TBC. The electrocardiogram, the levels of serum cardiac troponin T (cTnT), the activities of cardiac superoxide dismutase (SOD), malonaldehyde (MDA), and histopathology of heart tissue have been determined in each group. Meanwhile, the anti-RA effect of each group was investigated by paw swelling measurement and histopathological examination of synovial. To explore the underlying mechanism, we performed the pharmacokinetic studies of aconitine (AC) and deoxyaconitine (DE) in TBC group and TBC + HZ group by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) system. ResultsTBC co-administered with HZ could significantly inhibit the increased heart rate and the prolonged QTc interval induced by TBC (p < 0.01). And TBC + HZ group had lower levels of serum cTnT, cardiac MDA, and higher levels of cardiac SOD compared with TBC group (p < 0.01). In addition, the combination of TBC and HZ could preserve the anti-RA effect of TBC. Both TBC administration alone and TBC + HZ combination administration could effectively alleviate the paw swelling (p < 0.01). Furthermore, TBC co-administered with HZ could significantly decrease the area under the concentration-time curve (AUC(0-∞)) and maximum concentration (Cmax) of AC and DE comapred with TBC administration alone (p < 0.01 or p < 0.05). Meanwhile, it was observed that the time to reach the peak concentration (Tmax), elimination half-life (t1/2), mean retention time (MRT) of AC and DE in TBC group were significantly higher than those in TBC + HZ group (p < 0.01 or p < 0.05). ConclusionsTBC co-administered with HZ could reduce TBC-induced cardiotoxicty and preserve its anti-RA efficacy. The underlying mechanism is associated with the change of pharmacokinetic process of AC and DE.

Overexpression of NR4A2 alleviates renal and myocardial injury in diabetes nephropathy rats through the HDAC11/SPRY1 pathway.

Diabetic nephropathy (DN) remains the most prevalent cause of end-stage renal disease. Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a nuclear receptor with unique physiological characteristics. This study explored the molecular mechanism of NR4A2 in renal and cardiac functions of DN rats. A rat model of DN was established by intraperitoneal injection of streptozocin. NR4A2, histone deacetylase 11 (HDAC11), and sprouty 1 (SPRY1) expressions were detected. The fasting blood glucose (FBG), urinary albumin (UAlb), serum creatinine (Cr), and blood urea nitrogen (BUN) were determined. The pathological injury of renal and myocardial tissues was evaluated. The mitral early to late diastolic flow velocity ratio (E/A ratio), left ventricular ejection fraction (LVEF), left ventricular systolic function (LVSF), left ventricular internal dimension systole (LVIDs), and left ventricular internal diameter diastole (LVIDd) were tested, and the levels of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were examined. The enrichment of NR4A2 in HDAC11 promoter and enrichment of H3K27 acetylation in SPRY1 promoter were measured. NR4A2 and SPRY1 were downregulated while HDAC11 was upregulated in renal and myocardial tissues of DN rats. NR4A2 overexpression reduced FBG, UAlb, Cr, and BUN, alleviated pathological injury of renal and myocardial tissues, elevated the E/A ratio, LVEF, and LVFS, but reduced LVIDs, and decreased serum cTnI and CK-MB. NR4A2 depressed HDAC11 expression by binding to the HDAC11 promoter. HDAC11 repressed SPRY1 transcription by suppressing the H3K27ac level. HDAC11 overexpression or SPRY1 inhibition reversed the alleviating effect of NR4A2 overexpression on DN rats. NR4A2 was poorly expressed in DN rats. NR4A2 overexpression suppressed HDAC11 expression by binding to the HDAC11 promoter and enhanced SPRY1 transcription by enhancing H3K27 acetylation, thereby alleviating the renal and myocardial injury of DN rats.

Characterization of a novel polysaccharide from red ginseng and its ameliorative effect on oxidative stress injury in myocardial ischemia

BackgroundRed ginseng (RG) was widely used as traditional Chinese medicine (TCM) or dietary supplement. However, few researches had been reported on the red ginseng polysaccharide (RGP).MethodsIn this study, a novel heteropolysaccharide named RGP1-1 was fractionated sequentially by DEAE-52 column and Sephadex G-100 gel column. The primary structure of RGP1-1, including glycosyl linkages, molecular weight, monosaccharide composition, morphology and physicochemical property were conducted by nuclear magnetic resonance (NMR), gas chromatography-mass spectrometer (GC–MS), atomic force microscope (AFM), scanning electron microscope (SEM), differential scanning calorimetry-thermogravimetric analysis (DSC-TG) and so on. The effect of RGP1-1 in preventing and treating myocardial ischemia was evaluated by an animal model isoprenaline (ISO) induced mice.ResultsRGP1-1, with a homogeneous molecular weight of 5655 Da, was composed of Glc and Gal in the ratio of 94.26:4.92. The methylation and NMR analysis indicated the backbone was composed of → 1)-Glcp-(4 → and → 1)-Galp-(4 →, branched partially at O-4 with α-D-Glcp-(1 → residue. Morphology and physicochemical property analysis revealed a triple-helical conformation, flaky and irregular spherical structure with molecule aggregations and stable thermal properties of RGP1-1. And it contained 6.82 mV zeta potential, 117.4 nm partical size and polymerization phenomenon. Furthermore, RGP1-1 possessed strong antioxidant activity in vitro and in vivo, RGP1-1 could decrease cardiomyocyte apoptosis and myocardium fibrosis of mice in histopathology and it could decrease significantly the serum levels of cardiac troponin (cTnI), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA). Western blot analysis showed that RGP1-1 can increase the expression of main protein Nuclear factor E2-related factor 2(Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase-1(HO-1) and kelch-like ECH-associated protein1(keap1) in oxidative stress injure progress, and therefore regulate the pathway of Nrf2/HO-1.ConclusionThe above findings indicated that RGP1-1 had an improving effect on ISO-induced myocardial ischemia injury in mice, as novel natural antioxidant and heart-protecting drugs.

The Impact of HIIT on the cTnT Response in Sedentary Obese Young Men

Objective: Evaluation of the effect of 8 weeks of High-Intensity Interval Training (HIIT) on the serum level of cardiac troponin T (cTnT) in sedentary obese young men.&#x0D; Materials and Methods: Thirty sedentary men were randomly divided into 3 groups: the 30s HIIT training group (n=10), the 60s training group (n=10), and the control group (no exercise) (n=10). Interval training with 90 %VO2peak was done in 3 sessions for 8 weeks. cTnT was measured 5 times; pre-exercise, 4hrs, and 24hrs after the first session (4hF, 24hF), and 4hrs and 24hrs after the last training session (4hL, 24hL). ANOVA with repeated measures and Bonferroni post-hoc tests were used by SPSS 23 with a significance level of (P&lt; 0.05).&#x0D; Results: The significant increase in serum levels of cTnT in the post-tests of the 60s HIIT compared to the first 24hrs and the last 24hrs (P= 0.0001). But in the 30s group it was not significant compared to the other measurements (P≥ 0/05). In the 2 training groups, serum levels of cTnT in the last 4hr post-tests of the last week were not significantly different from the 4hrs post-tests of the first week (P≥ 0.05).&#x0D; Conclusion: It seems that none of these activities cause heart damage sustained, and changes in cTnT levels in two 4hrs compared to the first and last 24hrs of the 60s group may be due to reversible leakage of cardiac cell membranes, and may continuous exercise will reduce this reduction.

Carvedilol ameliorates dexamethasone-induced myocardial injury in rats independent of its action on the α1-adrenergic receptor

The current study aimed to investigate the cardiotoxic effect of dexamethasone-high-dose in rats, the therapeutic effect of carvedilol and the role of α1-adrenergic receptor (α1AR). The experiment involved 6 groups: control, dexamethasone (10 mg/kg), carvedilol (10 mg/kg), phenylephrine (1 mg/kg), phenylephrine plus carvedilol and propranolol (30 mg/kg). Drugs and vehicles were given for 7 days. Dexamethasone was given with the drugs in the last 4 groups. On the 8th-day and after overnight fasting, serum and cardiac samples were collected. Serum levels of cardiac troponin I and creatine kinase–myoglobin as well as cardiac levels of diacylglycerol, malondialdehyde, kinase activity of Akt, transforming growth factor-β, Smad3 and alpha smooth muscle actin were measured. Cardiac samples were also used for histopathological examination using hematoxylin–eosin and Sirius red stains, in addition to immunohistochemical examination using β-arrestin2 antibody. Dexamethasone induced cardiac injury via increasing oxidative stress, apoptosis and profibrotic signals. Carvedilol significantly reduced the dexamethasone-induced cardiotoxicity. Using phenylephrine, a competitive α1-agonist, with carvedilol potentiated the cardioprotective actions of carvedilol. Propranolol, a β-blocker without activity on α1ARs, showed higher cardiac protection than carvedilol. Dexamethasone-high-dose upregulates cardiac oxidative stress, apoptotic and profibrotic signals and induces cardiac injury. Blocking the α1-adrenergic receptor by carvedilol attenuates its cardioprotective effects against dexamethasone-induced cardiotoxicity.