Serum Levels Of Cardiac Troponin Research Articles

Serum cardiac and inflammatory biomarker levels following chemotherapy among female patients with breast cancer attending at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

BackgroundChemotherapy is a well-established therapeutic approach for several malignancies, including breast cancer (BCa). However, the clinical efficacy of this drug is limited by cardiotoxicity. Assessing multiple cardiac biomarkers can help identify patients at risk of adverse outcomes from chemotherapy.ObjectiveTo evaluate changes in serum cardiac and inflammatory biomarker levels following chemotherapy among female patients with BCa attending at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.MethodsAn experimental study design was used. Forty patients with breast cancer were selected using a convenience sampling method. After obtaining informed consent, 40 paired samples (40 samples before chemotherapy and 40 matched samples after three cycles of chemotherapy) were collected between May 2018 and March 2019. An Elecsys 2010 Troponin-T immunoassay analyzer was used to measure serum levels of cardiac troponin T (cTnT), creatinine kinase-myocardial band (CK-MB), C-reactive protein (CRP), and R and D systemic luminex performance assays were used to measure serum Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF- α). Data were analyzed using the SPSS version 23 package, and a p-value < 0.05 was considered statistically significant.ResultsAmong female patients with BCa receiving chemotherapy, 20%, 15%, and 35% of patients had elevated cTnT, CK-MB, and CRP levels, respectively, after three cycles of chemotherapy. In contrast, 15% of patients had baseline elevated CRP levels compared with their respective cutoff values. The mean serum cTnT, CK-MB, CRP, and TNF-α levels significantly increased (p < 0.05) compared with their respective baseline values. However, the IL-6 levels at baseline and after chemotherapy were not significantly different.ConclusionThis study revealed significant increases in cardiac and inflammatory biomarkers following chemotherapy among female patients with breast cancer in the study area. Therefore, cardiac biomarkers and echocardiography findings were used to assess functional abnormalities and treatment outcomes.

Effect of ticagrelor combined with metoprolol extended-release tablets on cardiac function and clinical prognosis in elderly patients with acute coronary syndrome after percutaneous coronary intervention

BackgroundAcute coronary syndrome (ACS) poses significant risks to older individuals. This study sought to assess the impact of combining ticagrelor and metoprolol extended-release tablets on clinical prognosis and cardiac function in elderly ACS patients following percutaneous coronary intervention (PCI).MethodsFrom February 2022 to February 2023, 90 elderly ACS patients who underwent PCI at our institution were retrospectively enrolled and divided into two groups: an observation group (OG) and a control group (CG), with 45 patients in each group. The CG received oral metoprolol extended-release tablets, while the OG received both oral metoprolol extended-release tablets and ticagrelor. Prognostic indicators and cardiac function were evaluated before and after treatment.ResultsThe treatment effectiveness rate in the OG was 97.78%, significantly higher than the CG's rate of 77.78% (P &amp;lt; 0.05). Post-treatment, the OG displayed notable improvements in cardiac function, including significantly higher left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), and cardiac index (CI) compared to the CG (P &amp;lt; 0.05). Both groups experienced enhanced exercise capacity, as evidenced by longer exercise duration (ED) and improved 6-min walking test (6MWT) results, with the OG showing superior gains (P &amp;lt; 0.05). Additionally, the OG had significantly higher serum levels of cardiac troponin T (cTnT) and creatine kinase isoenzyme (CK-MB) than the CG (P &amp;lt; 0.05). Decreases in serum levels of sICAM-1, MMP-9, and hs-CRP were observed in both groups, with more pronounced improvements in the OG (P &amp;lt; 0.05). The incidence of adverse prognostic events in the OG was significantly lower at 8.89%, compared to 37.78% in the CG (P &amp;lt; 0.05).ConclusionTicagrelor combined with metoprolol extended-release tablets can significantly improve cardiac function, motor performance, and quality of life in ACS patients after PCI. Additionally, it effectively increases myocardial injury markers and reduces serum inflammatory factor levels.

Clinical significance of elevated serum cardiac troponin T and associated risk factors in patients diagnosed with acute ischemic stroke

Objective: We explored the clinical significance and associated risk factors of increased levels of serum cardiac troponin T (cTnT) in individuals suffering from acute ischemic stroke (AIS). Methods: Our study subjects consisted of patients who were admitted with AIS within 48 hours of its onset. These study participants were categorized based on their levels of cTnT into two groups: normal cTnT group and elevated cTnT group. We collected and subjected a range of data to statistical analysis, including general clinical traits, medical history, laboratory test results, electrocardiograms, imaging scans, and medical records like the National Institute of Health Stroke Scale (NIHSS) scores of the patients. Results: Out of the 232 patients diagnosed with AIS, 84 individuals (36.21%) exhibited raised levels of cTnT. When comparing this elevated cTnT cohort to the group with regular cTnT levels, those with elevated cTnT were older [with a median age of 76 year (interquartile range: 67 to 83) as compared to 70 year interquartile range: 61 to 79), P = 0.002], and they presented with higher NIHSS scores upon admission [8.5 (interquartile range: 4 to 14) compared to 5 (interquartile range: 2 to 9), p = 0.002]. In addition, a larger percentage of patients in the elevated cTnT group had both coronary artery disease (23.81% vs. 7.43%, P &lt; 0.001) and cardiac insufficiency (25.00% vs. 3.38%, P &lt; 0.001) as comorbidities. Meanwhile, the elevated cTnT group also displayed a higher occurrence of electrocardiogram abnormalities, including bundle branch block (29.76% vs. 9.46%, P &lt; 0.001) and atrial fibrillation (32.14% vs. 11.49%, P &lt; 0.001), in comparison to the normal cTnT group. The clinical data and related laboratory indicators of patients were collected for risk factor analysis, which showed that bundle branch block [odds ratio (OR) = 4.17, 95% confidence interval (95%CI) = 1.43–12.16), log to base 10 N-terminal pro-brain natriuretic peptide (Log10NT-proBNP; OR = 3.41, 95%CI = 1.62-7.16), cystatin C (OR = 6.86, 95%CI = 2.01–23.43), and neutrophil/lymphocyte ratio (OR = 1.13, 95%CI = 1.02–1.25) were independent risk factors for elevated cTnT in patients with AIS. Conclusions: Older patients with AIS who had higher levels of cTnT exhibited more severe neurological impairments and a greater number of comorbidities. Furthermore, an elevated cTnT in patients with AIS may be linked to cardiac insufficiency, changes in kidney function, and signs of inflammation.

Role of del Nido Cardioplegia Solution in Prolonged Aortic Cross-clamp Cardiac Surgery: A Prospective Study.

The myocardial-protective effect of del Nido cardioplegia solution was evaluated in adult patients undergoing prolonged aortic cross-clamping during cardiac surgery. Prospective cohort. Single-center tertiary academic medical center. A total of 462 patients scheduled for cardiac surgery under cardiopulmonary bypass with an expected aortic cross-clamp time >120 minutes between January 2020 and January 2024 were enrolled. Patients with an expected aortic cross-clamp time >120 minutes were randomly assigned to low- and high-risk del Nido and Buckberg groups, with 112 patients in each group. Serum levels of cardiac troponin T and creatine kinase-MB were measured at 1, 24, and 48 hours after operation. The occurrence of atrial fibrillation within 48 hours postoperatively and other intraoperative and postoperative parameters were recorded. No significant differences were observed in preoperative parameters between the groups. The level of cardiac troponin T was significantly higher in the low-risk del Nido group than in the Buckberg group at 24 hours postoperatively (p < 0.05). However, no significant differences were observed in cardiac troponin T or creatine kinase-MB levels at the other time points. The incidence of postoperative atrial fibrillation in the Buckberg group at 48 hours was significantly higher than the del Nido group in both the low- and high-risk groups (p < 0.05). The incidence of postoperative atrial fibrillation at 48 hours was significantly lower in the del Nido group than in the Buckberg group. del Nido cardioplegia solution can be safely used for high-risk patients undergoing prolonged aortic cross-clamping.

Abstract 4138606: Toll-like Receptor 4 Signaling Establishes Trained Innate Immunity Through Interferon-Mediated Epigenetic Modifications Leading to Cardioprotection in a Stress-induced Cardiomyopathy Model

Introduction: The mechanisms responsible for establishing preconditioning-induced cardioprotection remain unknown. We have shown that a high dose of isoproterenol (ISO) induces cardioprotection against a second ISO dose in mice. The durability of protection and the lack of an innate immune response suggests trained immunity as a novel cardioprotective mechanism. Hypothesis: We hypothesize that cardioprotection is conferred through trained immunity, by interferon signaling downstream of necrotic cardiac material-mediated Toll-like receptor 4 (TLR4) activation. Methods: Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent, and challenged with 300 mg/kg ISO 7 days later. Mice were assessed by 2-D echocardiography, serum cardiac troponin levels, flow cytometry immune cell counts, and Multiome (single nuclei RNA+ATAC) sequencing. Results: The TLR4 agonist lipopolysaccharide (LPS) induced cardioprotection against ISO injury, with mice having enhanced survival (P=0.049) and no changes in cardiac troponin levels (P&gt;0.99), cardiac neutrophil influx (P&gt;0.99) or left ventricular motion (P=0.057) relative to baseline values before injury. Treating LPS-injected mice with β-glucan reversed the effects of LPS on immune cells and abolished cardioprotection. Multiome analysis of genes linked to chromatin peaks with increased accessibility in LPS+vehicle (protected) compared to LPS+β-glucan and diluent control (non-protected) hearts revealed the interferon pathway to be up-regulated across all major cell types. Modulation of interferon signaling with monoclonal antibodies against type 1+2 interferon receptors abolished cardioprotection in LPS-treated mice, whereas pre-treatment with recombinant type 1+2 interferons induced cardioprotection. Importantly, interferon-treated hearts shared similar chromatin accessibility features and enriched transcription factor motifs, including interferon-specific motifs, with LPS-protected hearts across cell types, particularly among non-cardiomyocytes. Conclusions: TLR4-induced interferon signaling is sufficient and in part necessary for cardioprotection against ISO injury. Moreover, our findings show that epigenetic modifications downstream of interferon signaling lead to cardioprotection consistent with trained innate immunity.

Moderate-intensity training can ameliorate the process of cardiac apoptosis induced by lithium drug consumption in male Wistar rats

Background and objectiveLithium medication, given its significant role in the treatment or reduction of psychiatric disorders, may exert adverse effects on cardiac tissue. Therefore, this study aimed to investigate the effects of different exercise training intensities on the process of cardiac apoptosis and serum levels of cardiac troponin I (cTnI) resulting from lithium administration in male Wistar rats. MethodologyIn the present experimental study, 35 male Wistar rats were randomly divided into five groups (n=7); Control (CTL), Lithium (Li), High-Intensity training + lithium (HIT-Li), Moderate-Intensity training + lithium (MIT-Li), and Low-Intensity training + lithium (LIT-Li). Lithium drug (dose of 40 mmol/kg dry food weight) and exercise training (5 days per week) were administered for eight weeks. Serum levels of cTnI, mRNA expression of Bcl-2, Bax, and Caspase-3, and histopatholigical changes were assessed by using the ELISA method, Real-Time PCR, and H&E staining, respectively. ResultsThe expression of the Bcl-2 gene was significantly increased in the LIT-Li group compared to the Li group (P = 0.003). Serum levels of cTnI were considereably higher in the Li group compared to the MIT-Li group (P = 0.0001). The expression of the Bax gene, in the LIT-Li, HIT-L, and Li groups, significantly increased compared to the MIT-Li group (P = 0.0001). Histopathological scores decreased in MIT-Li compared to Li group (P = 0.001). ConclusionIt seems that among different exercise intensities, the greatest protective effect against lithium consumption can be observed with moderate exercise intensity, which may potentially modulate factors influencing cardiac apoptosis and reduce lithium toxicity in the cardiac tissue of rats.

MiR-361-3p overexpression promotes apoptosis and inflammation by regulating the USP49/IκBα/NF-κB pathway to aggravate sepsis-induced myocardial injury.

Sepsis is a major cause of in-hospital death, particularly in the intensive care unit. A huge amount of effort has been put into identifying reliable biomarkers to improve the prognosis of patients with sepsis. Among the numerous candidates, microRNAs have attracted attention because of their promising prognostic value. Multiple miRNAs have been suggested to play vital roles in manipulating the nuclear factor-kappa B (NF-κB) pathway, a key factor involved in sepsis. In this study, we attempted to elucidate the potential functions of miR-361-3p in sepsis-induced myocardial injury in vivo and in vitro. A sepsis model was established by cecal ligation and puncture (CLP) in rats and by lipopolysaccharide (LPS) in H9c2 cells. The functions of miR-361-3p were revealed by assessing the level of biomarkers of myocardial injury and inflammation by Enzyme-linked immunosorbent assay, as well as the apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and flow cytometry. Binding of miR-361-3p and the 3' untranslated region of ubiquitin-specific peptidase 49 (Usp49) was revealed by Dual luciferase reporter gene assay. The interaction of USP49 and its downstream target NF-κB inhibitor alpha (IκBα) was revealed by Co-immunoprecipitation and western blot analysis. miR-361-3p antagomir inhibited myocardial injury and inflammation in CLP-induced rats, as evidenced by a decrease in the serum levels of cardiac troponin I, creatine kinase-MB, interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha and cell apoptosis. However, miR-361-3p agomir aggravated sepsis-induced myocardial injury. Moreover, miR-361-3p inhibition induced the inhibition of LPS-induced apoptosis and inflammation in H9c2 cells. miR-361-3p could inhibit the expression of Usp49 by binding to its 3' untranslated region. Furthermore, we demonstrated that Usp49 binds to IκBα and mediates its deubiquitination, leading to the stabilization of IκBα, which results in the cytoplasmic accumulation of NF-κB and eventually the suppression of NF-κB activity. Taken together, our data demonstrate that miR-361-3p overexpression promotes apoptosis and inflammation by regulating the USP49/IκBα/NF-κB pathway to aggravate sepsis-induced myocardial injury.

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

Myocardial protection with cardioplegia is a crucial approach to mitigate myocardial damage during coronary bypass grafting surgery (CABG) with cardiopulmonary bypass (CPB). The major component of the del Nido cardioplegia solution, Plasma-Lyte A, is difficult to obtain in Iran due to high cost. The objective of the current study was to study if the lactated Ringer's solution as the base for del Nido solution (LR DN) usage is a viable option as a substitute for Plasma-Lyte A in adult patients presenting for CABG surgery. The present prospective, randomized, blinded study was performed on 18-75-year-old patients ejection fraction (EF)>35% undergoing CABG with CPB. 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), the type and dosage of inotrope agents, EF, rate of arrhythmia after clamp removal and lactate level were measured and compared between patients of LR DN and PL DN groups. 109 patients were recruited. There were no statistically significant differences between groups for cardiopulmonary bypass times, cardiac enzymes, transfusion requirements, and arterial blood gases. There was no mortality for study patients. 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 24h post-ICU. 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). We concluded that the 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 PL base for patients presenting for CABG surgery.

Dibenzazepine, a γ-Secretase Enzyme Inhibitor, Protects Against Doxorubicin-Induced Cardiotoxicity by Suppressing NF-κB, iNOS, and Hes1/Hey1 Expression.

Doxorubicin (DOX) is an effective chemotherapeutic drug; however, its cardiotoxicity and resistance compromise its therapeutic index. The Notch pathway was reported to contribute to DOX cancer resistance. The role of Notch pathway in DOX cardiotoxicity has not been identified yet. Notch receptors are characterized by their extracellular (NECD) and intracellular(NICD) domains (NICD). The γ-secretase enzyme helps in the release of NICD. Dibenzazepine (DBZ) is a γ-secretase inhibitor. The present study investigated the effect of Notch pathway inhibition on DOX cardiotoxicity. Twenty-four male Wistar rats were divided into four groups: control group, DOX group, acute cardiotoxicity was induced by a single dose of DOX (20 mg/kg) i.p., DOX (20 mg/kg) plus DBZ group, and DBZ group. The third and fourth groups received i.p. injection of DBZ daily for 14 days at 2 mg/kg dose. DOX cardiotoxicity increased the level of serum creatine kinase-MB and cardiac troponin I, and it was confirmed by the histopathological examination. Moreover, the antioxidants glutathione peroxidase and superoxide dismutase levels were markedly decreased, and the inflammatory markers, inducible nitric oxide synthase, nuclear factor-ķB, and tumor necrosis factor-α were markedly increased. Furthermore, DOX increased BAX protein and downregulated BCL-2. In addition, DOX upregulated Notch pathway-related parameters: Hes1 and Hey1 mRNA levels, and increased Hes1 protein levels. DBZ ameliorated DOX-induced cardiotoxicity, evidenced by reducing the cardiac injury biomarkers, improving cardiac histopathological changes, correcting antioxidant levels, and reducing inflammatory and apoptotic proteins. Our study indicates the protective effect of Notch inhibitor against DOX-induced cardiotoxicity.

Effects of Methanol Extract of Celery (Apium graveolens) Leaf on Ethanol-Induced Left Ventricular Changes in Wistar Rats

Background: Alcohol consumption is associated with several cardiovascular diseases such as heart failure, left ventricular hypertrophy, as well as with other disorders. This study was designed to determine the cardioprotective effect of celery (Apium graveolens) extract in attenuating perturbations arising from alcohol ingestion on left ventricular injury in adult Wistar rats.  Methods: Thirty male Wistar rats weighing 120g -160g were used for this study. The rats were divided into six (6) groups A, B, C, D, E &amp;F five (5) rats each. The rats in group (A) served as control and received standard pellet, while groups B, C, D, E and F were administered orally with 8ml/kg b. w of ethanol and 100mg/kg, 150mg/kg, 200mg/kg of methanol extract of Apium graveolens (MEAG) were given to group C, D and E and 25mg of propranolol was given to group F orally. Group A and B were administered with 2ml/kg b. w distilled water.  Results: The relative heart weight, level of serum cardiac troponin I and left ventricular wall thickness of the ethanol-induced rats were significantly increase (F = 7.64; p = 0.002), (F = 22.66; p = 0.001) and (F = 85.29; p &lt; 0.001) when compared with the control and across all experimental groups in this study. Group treated with MEAG also showed regular striations.Conclusion: This study indicates that MEAG has cardioprotective effects on these perturbations.

Protective effect and mechanism of methylene blue on myocardial injury in rats with sepsis

To explore the protective effect of methylene blue (MB) on myocardial injury in sepsis and its possible signaling pathway. A total of 32 female Wistar rats were randomly divided into sham operation group, sepsis model group, MB prevention group, and MB treatment group, with 8 rats in each group. The MB prevention group was injected with 15 mg/kg MB in the peritoneal cavity 6 hours before modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. The sepsis model was established by cecal ligation puncture (CLP); the sham operation group was only subjected to an exploratory incision without ligation or puncture of the caecum. The MB treatment group was injected with 15 mg/kg MB in the peritoneal cavity 0.5 hours after modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. Peripheral blood and myocardial tissue were collected from each group at 6 hours and 12 hours after modeling. Histological changes in the myocardial tissue were observed under the microscope; the levels of serum cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA); and the expressions of inducible nitric oxide synthase (iNOS), light chain 3 (LC3), and p62 in the myocardial tissue were detected by Western blotting. Under light microscopy, no obvious abnormalities were found in the myocardium of the sham operation group; the myocardium of the sepsis model group showed obvious inflammatory changes; the myocardium of the MB prevention group showed mild inflammatory changes at 6 hours after modeling, severe inflammatory changes at 12 hours but less severe than the sepsis model group; the myocardium of the MB treatment group showed more obvious inflammatory changes at 6 hours after modeling but less severe than the MB prevention group at 12 hours after modeling, and the inflammatory changes at 12 hours after modeling were alleviated but more severe than the 6 hours after modeling in MB prevention group. Compared with the sham operation group, the levels of cTnI, CK-MB, TNF-α and IL-6 in the MB prevention group at 6 hours and 12 hours after modeling were not significantly changed; compared with the sepsis model group, the cTnI, CK-MB, TNF-α and IL-6 levels in the MB treatment group at 6 hours and 12 hours after modeling were significantly lower [cTnI (ng/L): 175.03±12.26, 411.24±21.20 vs. 677.79±43.95 at 6 hours of modeling, 159.52±6.44, 412.46±32.94 vs. 687.61±55.09 at 12 hours of modeling; CK-MB (ng/L): 8.38±0.49, 16.87±1.41 vs. 24.87±1.74 at 6 hours of modeling, 7.94±0.30, 16.66±2.03 vs. 25.02±7.29 at 12 hours of modeling; TNF-α (ng/L): 26.98±3.31, 46.95±3.74 vs. 112.60±6.64 at 6 hours of modeling, 31.31±5.83, 90.97±5.14 vs. 149.30±4.67 at 12 hours of modeling; IL-6 (ng/L): 40.86±4.48, 128.90±3.14 vs. 248.90±12.76 at 6 hours of modeling, 80.13±7.94, 190.40±9.56 vs. 288.90±6.01 at 12 hours of modeling; all P < 0.05]. Western blotting showed that compared with the sham operation group, the protein expressions of iNOS, LC3, and p62 in the sepsis model group were significantly higher at 6 hours and 12 hours after modeling; compared with the sepsis model group, the protein expressions of iNOS, LC3, and p62 in the MB treatment group and MB prevention group were significantly lower at 6 hours and 12 hours after modeling (iNOS/GAPDH: 0.38±0.04, 0.60±0.04 vs. 0.77±0.04 at 6 hours of modeling; 0.38±0.02, 0.66±0.04 vs. 0.79±0.05 at 12 hours of modeling; LC3/GAPDH: 0.13±0.07, 0.42±0.07 vs. 1.05±0.16 at 6 hours of modeling; 0.08±0.02, 0.25±0.03 vs. 0.48±0.09 at 12 hours of modeling; p62/GAPDH: 0.17±0.05, 0.44±0.10 vs. 1.19±0.07 at 6 hours of modeling; 0.07±0.00, 0.28±0.08 vs. 0.69±0.02 at 12 hours of modeling; all P < 0.05). MB can reduce myocardial oxidative stress by inhibiting iNOS expression and mitochondrial autophagy in septic rats, thereby alleviating myocardial damage in sepsis, and has protective effect on myocardial damage in sepsis.

Calcium Dibutyryl Adenosine Cyclophosphate Enhances the Effect of Metoprolol in Treating Older Adults With Heart Failure Combined With Arrhythmia

To explore the effect and safety of calcium dibutyryl adenosine cyclophosphate (dbcAMP-Ca) combined with metoprolol in the treatment of older adults with heart failure combined with arrhythmia. A total of 102 elderly patients with heart failure combined with arrhythmia were enrolled in our hospital between February 2021 and April 2023. The list of patients enrolled was entered into a random database by independent staffs not involved in the study and random assignment sequences were generated by the SAS9.4 software. Then, the 102 elderly patients were divided into a control group ( n=51) and an experimental group ( n=51). Patients in the control group were given metoprolol at an initial dose of 6.25 mg/d, which was gradually increased to the target dose of 25 mg/d. Patients in the experimental group were given 40 mg of dbcAMP-Ca once a day via intravenous drip in addition to the treatment given to the control group. Both groups were treated for 4 weeks. The rate of effective response to clinical treatment (the number of cases achieving significant effects and those achieving some effects divided by the total number of cases in the group) was defined as the main outcome index. Secondary indexes included cardiac function, heart rate variability, exercise ability, hemorheology, myocardial injury indexes, inflammatory indexes, and the occurrence of adverse reactions. The rate of effective response to clinical treatment was higher in the experimental group than that in the control group (94.12% [48/51] vs. 78.43% [40/51], P<0.05). After treatment, the left ventricular end-diastolic and end-systolic dimensions (LVEDD and LVESD) and the interventricular septal thickness (IVS) were lower in the experimental group than those in the control group, while the left ventricular ejection fraction (LVEF) and the stroke volume (SV) were higher in the experimental group than those in the control group ( P<0.05). In terms of heart rate variability after treatment, the standard deviation of all the normal-to-normal intervals/the average of all the normal-to-normal intervals (SDNN/SDANN), the percentage of NN50 in the total number of normal-to-normal intervals (PNN50%), and the root mean square of the differences between adjacent normal-to-normal intervals/root mean square differences of successive R-R intervals (RMSSD) were higher in the experimental group than those in the control group ( P<0.05). In terms of exercise capacity after treatment, the subjects in the experimental group covered more distance in the 6-min walk test than those in the control group did ( P<0.05). In terms of the hemorheology indexes after treatment, the levels of platelet aggregation rate (PAgT), fibrinogen (FIB), erythrocyte sedimentation rate (ESR), and whole blood viscosity (ηb) were lower in the experimental group than those in the control group ( P<0.05). In terms of the myocardial injury indexes after treatment, the levels of serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) and cardiac troponin I (cTnI) were lower in the experimental group than those in the control group, while the levels of insulin-like growth factor 1 (IGF-1) and cardiotrophin 1 (CT-1) were higher in the experimental group than those in the control group ( P<0.05). In terms of the inflammatory indexes after treatment, the levels of interleukin-6 (IL-6), high-sensitive C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) were lower in the experimental group than those in the control group ( P<0.05). The incidence of adverse reactions in the experimental group (9.80%) and that in the control group (7.84%) were comparable ( P>0.05). The use of dbcAMP-Ca in addition to metoprolol can effectively improve cardiac function, heart rate variability, and exercise tolerance, while inhibiting inflammatory response in elderly patients with heart failure combined with arrhythmia, with high medication safety. The combination medication shows better safety and therapeutic effects than those of metoprolol used alone.

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 lipidlowering 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