Creatine Kinase-myocardial Band Research Articles

Prognostic Value of Cardiac Biomarkers in Naturally Infected Anaplasmosis, Theileriosis and Babesiosis Associated Cardiac Damage in Dairy Cows

Background: Treating severe forms of hemoprotozoan diseases are challenging. Myocardial damage in such parasitic diseases are often neglected during routine clinical practice. The present study was designed to assess the deleterious effects of naturally infected cattle with hemoprotozoa on the cardiovascular system and the consequent myocardial involvement. Methods: The positive animals were subjected to clinical examination, haemato-biochemical analysis, estimation of cardiac biomarkers such as cardiac troponin I (cTnI), creatine kinase myocardial band (CK-MB), lactic dehydrogenase enzyme (LDH), ultrasonography and Base Apex Electrocardiography to find their prognostic significance in cattle with hemolytic anemia. Result: A significant change in these biomarkers was noticed post treatment, indicating their utility as prognostic markers as well as to assess the efficacy of therapy.

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

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

Clinical outcomes and characteristics of acute myocardial infarction patients with developing fever after percutaneous coronary intervention

The incidence of fever complicating percutaneous coronary intervention (PCI) is rare. However, little is known regarding the cause of fever after PCI. Therefore, this study aimed to determine the clinical characteristics of patients with acute myocardial infarction (AMI), with or without fever, after PCI. We enrolled a total of 926 AMI patients who underwent PCI. Body temperature (BT) was measured every 4 hours or 8 hours for 5 days after PCI. Patients were divided into two groups according to BT as follows: BT<37.7°C (no-fever group) and BT ≥37.7°C (fever group). The 2 years clinical outcomes were compared subsequently. Fever after PCI was associated with higher incidence of major adverse cardiac events (MACE) (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.07-2.28; <i>P</i>=0.021), all-cause death (HR, 2.32; 95% CI, 1.18-4.45; <i>P</i>=0.014), cardiac death (CD) (HR, 2.57; 95% CI, 1.02-6.76; <i>P</i>=0.049), and any revascularization (HR, 1.69; 95% CI, 1.02-2.81; <i>P</i>=0.044) than without fever. In women, prior chronic kidney disease, lower left ventricular (LV) ejection fraction, higher LV wall motion score index, white blood cell count, peak creatine kinase-myocardial band level, and longer PCI duration were associated with fever after PCI. Procedures such as an intra-aortic balloon pump, extracorporeal membrane oxygenation, continuous renal replacement therapy, central and arterial line insertion, and cardiopulmonary resuscitation were related to fever after PCI. Fever after PCI in patients with AMI was associated with a higher incidence of MACE, all-cause death, CD, and any revascularization at the 2 years mark than in those without fever.

Predictors of the Outcomes Following the Tocilizumab Treatment for Severe COVID-19.

Background: Tocilizumab is used in severe COVID-19 yet has significant rates of treatment failure.Objectives: This retrospective study aimed to identify early predictors of the response to tocilizumab therapy.Methods: Biochemical and clinical characteristics of adult patients who received tocilizumab for severe COVID-19 pneumonia were retrospectively examined. A multivariable logistic regression model was constructed to identify factors that could predict the failure of tocilizumab therapy. A predictive nomogram was also created using the selected model.Results: Out of 101 eligible patients, 30 had treatment failure, and 71 survived on a 28-day follow-up. The partial pressure of oxygen to fraction of inspired oxygen ratio (PFR) on the day of tocilizumab administration (100 vs 80.5), lactate dehydrogenase (LDH; 668 vs 507 U/L), neutrophil-to-lymphocyte ratio (NL ratio; 24.7 vs 10), and creatine kinase myocardial band (CKMB; 30.9 vs 22.7 U/L) were significantly different among the non-survivors and survivors, respectively. A logistic regression model was created, identifying LDH, NL ratio, pro-brain natriuretic peptide (ProBNP), and PFR on the day of tocilizumab administration as best predictors of mortality with an optimism-corrected area under the receiver operator characteristics (ROC) curve of 0.82. The model-implied odds ratios for mortality were 1.89 (95% CI 1.13-3.15) for every 100 U/L rise in serum LDH, 2.29 (95% CI 2.2-4.39) for every 10 unit rise in NL ratio, 1.23 (95% CI 0.95-1.58) for every 100 pg/ml increase in ProBNP, and 0.36 (95% CI 0.13-0.95) for every mmHg rise in PFR at intervention.Conclusion: This study identified NL ratio, LDH, CKMB, and PFR at intervention as important markers of risk of treatment failure following the tocilizumab therapy. A multivariable logistic regression model including LDH, NL ratio, ProBNP, and PFR at intervention best predicted the risk of mortality in patients with severe COVID-19 pneumonia treated with tocilizumab.

Comparison of post-procedural rise of cardiac biomarkers after implantation of an everolimus-eluting bioresorbable vascular scaffold versus everolimus-eluting metallic stent in patients with long/diffuse LAD disease

Objectives This study sought to evaluate the incidence and the mechanism of post-procedural cardiac biomarker (CB) rise following device implantation. Background A fully bioresorbable Absorb scaffold, compared with everolimus-eluting metallic stents (EES), might be associated with a higher incidence of periprocedural myocardial injury. Methods Prospective nonrandomized comparative study enrolled 52 patients with stable myocardial ischemia with diffuse/ long LAD lesion for either an everolimus-eluting bioresorbable vascular (BVS) scaffold (22 patients) or an EES (30 patients), 3 types of CB (creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and troponin) were obtained before and after procedure. Per protocol, periprocedural myocardial infarction (PMI) was defined as CK rise >2 the upper limit of normal with CK-MB rise. Results Incidence of side branch occlusion (SBO) and any anatomic complications assessed by angiography was similar between the 2 treatment arms (SBO: Absorb: 4.5% vs. Xience: 6.7%, p=1; One PMI with acute instent thrombosis occurred in EES group. Dissection occurred in only 1 patient in BVS arm after stent implantation; this event was not associated with elevated cardiac biomarkers. One patient had PMI in BVS arm with no angiographic complications to explain it.

The efficacy of combined therapy of qingfeiPaidu capsule and lianhuaqingwen capsule nursing interventions for hospitalized patients with COVID-19: A retrospective study of medical records.

Coronavirus disease-19 (COVID-19) caused a global pandemic burden, affecting hundreds of thousands of individuals, having life-threatening outcomes. Traditional Chinese Medicine plays a crucial role in the treatment of patients with COVID-19. The purpose of this study was to investigate the efficacy of combined therapy of qingfeiPaidu (QFPD) capsule and lianhuaqingwen (LHQW) capsule nursing interventions in the treatment of patients with COVID-19. A total of 318 patients with COVID-19 were enrolled and randomly received QFPD (n = 106), LHQW (n = 106), and QFPD-LHQW (n = 106). The clinical characteristics of COVID-19, the total lung severity scores, and blood laboratory indices were recorded in each patient in each group before treatment and at the end of treatment.The outcomes demonstrated that QFPD-LHQW group shortened the length of hospitalization, decreased C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels, and improved clinical symptoms, pulmonary inflammation, and prognosis. At the end of treatment, inflammation, immune function, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in 3 groups compared with baseline. All patients met the discharge criteria after 30-day treatment in 3 groups. Combined therapy of QFPD and LHQW demonstrated significant anti-inflammatory effects compared with those of only QFPD or LHQW in patients with mild and moderate COVID-19. The combined therapies may alleviate clinical symptoms of COVID-19 patients by improving inflammation and immune function.

Influence of the cardio-ankle vascular index on chronic-phase left ventricular dysfunction after ST-segment elevation myocardial infarction.

This study aimed to investigate the possible influence of arterial stiffness assessed by the cardio-ankle vascular index (CAVI) on chronic-phase left ventricular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). A total of 208 consecutive patients with first STEMI (age, 64 ± 11 years; 86% men) who underwent reperfusion therapy within 12 h of onset were enrolled. We analysed arterial stiffness by measuring CAVI in a stable phase after admission and performed two-dimensional echocardiography at baseline and 7 months' follow-up. Subsequently, we assessed left ventricular global longitudinal strain (LV-GLS) to evaluate left ventricular function. A total of 158 (75.9%) patients underwent baseline cardiac magnetic resonance (CMR). We estimated left ventricular infarct size by measuring peak levels of creatine kinase-myocardial band (CK-MB), and CMR-late gadolinium enhancement (LGE). On the basis of the median CAVI value, the patients were allocated into high CAVI (CAVI ≥ 8.575) and low CAVI (CAVI < 8.575) groups. The groups showed no statistically significant differences in LV-GLS at baseline (-13.5% ± 3.1 vs. -13.9% ± 2.7%, P = 0.324). However, LV-GLS was significantly worse in the high CAVI group than in the low-CAVI group at 7 months (-14.0% ± 2.9 vs. -15.6% ± 3.0%, P < 0.001). Stratified by CAVI and peak CK-MB or LGE, the four groups showed significant differences in LV-GLS at 7 months after STEMI (both P < 0.001). Multivariate linear regression analysis with the forced inclusion model showed that CAVI was an independent predictor of LV-GLS at 7 months ( P = 0.015). CAVI early after STEMI onset was significantly associated with chronic-phase LV-GLS. In addition, combining CAVI with CK-MB or LGE improves its predictive ability for evaluation of chronic-phase LV-GLS. Thus, the arterial stiffness assessment by CAVI was an important factor related to chronic-phase left ventricular dysfunction after the first STEMI.

Effects of perilipin-5 on lipid metabolism and high-sensitivity cardiac troponin I.

SUMMARYOBJECTIVE:Heart attack is one of the most common causes of sudden death in adults. Therefore, early detection of heart attack and investigation of potential new biomarkers are of great importance. We investigated whether perilipin-5 is a potential biomarker by examining changes in perilipin-5 serum levels along with high-sensitivity cardiac troponin I during a heart attack.METHODS:The subjects were divided into two groups: (1) control group and (2) patients with heart attack, with 150 people in each group. High-sensitivity cardiac troponin I, perilipin-5, total oxidant status, malondialdehyde, reduced glutathione, and superoxide dismutase levels in serum samples were measured. In addition, perilipin-5 mRNA expressions and protein levels were analyzed.RESULTS:There was no overall statistical difference between the demographic characteristics of the groups. However, high-density lipoprotein, creatine kinase, Creatine kinase myocardial band, aspartate amino transferase, lactate dehydrogenase, and calcium levels were higher in the heart attack group compared to the control group. We found that the high-sensitivity cardiac troponin I and perilipin-5 levels increased in the patients with heart attack (p<0.0001) compared to control. Although there was an insignificant increase in malondialdehyde levels in the heart attack group (p>0.05), there was a 35.9% increase in total oxidant status levels and a 33.5 and 24.1% decrease in glutathione and superoxide dismutase levels, respectively (p<0.01), compared to control. Perilipin-5 mRNA and protein levels in heart attack patients increased by 48.2 and 23.6%, respectively, compared to the control group (p<0.01).CONCLUSION:Our results showed that perilipin-5 together with high-sensitivity cardiac troponin I could be a promising biomarker in heart attack.

COVID-19 Severity and Mortality in Two Pandemic Waves in Poland and Predictors of Poor Outcomes of SARS-CoV-2 Infection in Hospitalized Young Adults.

SARS-CoV-2 variants pose a significant threat to global public health. However, their influence on disease severity, especially among young adults who may exhibit different clinical characteristics, is debatable. In this retrospective study of 229 young adults hospitalized with COVID-19, we investigated the differences between Poland’s second and third waves of the pandemic. To identify potential predictors of severe COVID-19 in young adults, we analyzed patient characteristics and laboratory findings between survivors and non-survivors and we performed logistic regression to assess the risk of death, mechanical ventilation, and intensive care unit treatment. We found no increase in COVID-19 severity comparing the third and second waves of the pandemic, indicating that the alpha variant had no influence on disease severity. In addition, we found that factors, such as obesity, comorbidities, lung involvement, leukocytosis, neutrophilia, lymphopenia, higher IG count, the neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin, interleukin-6, D-Dimer, lactate dehydrogenase, high-sensitive troponin I, creatine kinase-myocardial band, myoglobin, N-terminal-pro-B-type natriuretic peptide, creatinine, urea and gamma-glutamyl transferase, lower estimated glomerular filtration rate, albumin, calcium and vitamin D3, possibly a decrease in red blood cell counts, hemoglobin and hematocrit, and an increase in creatine kinase during hospitalization may be associated with poor outcomes of COVID-19.

Assessment toxic effects of exposure to 3-indoleacetic acid via hemato-biochemical, hormonal, and histopathological screening in rats

The current study purposed to investigate the 3-indoleacetic acid (IAA) possible adverse impacts on hematological parameters, hepatorenal function, cardiac, and skeletal muscles as well as testes of rats and histopathological alterations of respective organs and to determine the extent of reversing any adverse impacts occurred in animals after IAA withdrawal. Rats were exposed orally to 500 mg/kg BW by gastric intubation once daily for 14 days, after which one-half was sacrificed and the remaining half left for a further 14 days without IAA exposure. The exposure of rats to IAA produced anemia, leukopenia, neutrophilia, lymphopenia, and a significant increase in activities of serum transaminase, gamma-glutamyl transferase, creatine kinase-myocardial band, creatine kinase-muscle type, and levels of serum creatinine, sodium, chloride, and potassium. Furthermore, serum levels of testosterone, gonadotropins, and leptin significantly declined. The changes in most of measured parameters continued after IAA withdrawal. Histopathological alterations in different tissues supported these changes. In conclusion, subacute exposure to IAA at a high concentration could exert hematotoxicity and toxic effects on many soft organs and its withdrawal led to incomplete recovery of animals. Thus, IAA should be used cautiously as extensive use of it at high concentrations can cause harmful effects on the environment, animals and human beings.

A NOMOGRAM FOR PREDICTING PATIENTS WITH SEVERE HEATSTROKE.

Background: No predictive models are currently available to predict poor prognosis in patients with severe heatstroke. We aimed to establish a predictive model to help clinicians identify the risk of death and customize individualized treatment. Methods: The medical records and data of 115 patients with severe heatstroke hospitalized in the intensive care unit of Changzhou No. 2 People's Hospital between June 2013 and September 2019 were retrospectively analyzed for modeling. Furthermore, data of 84 patients with severe heatstroke treated at Jintan No. 1 People's Hospital from June 2013 to 2021 were retrospectively analyzed for external verification of the model. We analyzed the hematological parameters of the patients recorded within 24 h of admission, which included routine blood tests, liver function, renal function, coagulation routine, and myocardial enzyme levels. Risk factors related to death in patients with severe heatstroke were screened using Least Absolute Shrinkage and Selection Operator regression. The independent variable risk ratio for death was investigated using the Cox univariate and multivariate regression analyses. The nomogram was subsequently used to establish a suitable prediction model. A receiver operating characteristic curve was drawn to evaluate the predictive power of the prediction model and the Acute Physiology and Chronic Health Evaluation (APACHE II) score. In addition, decision curve analysis was established to assess the clinical net benefit. The advantages and disadvantages of both models were evaluated using the integrated discrimination improvement and Net Reclassification Index. A calibration curve was constructed to assess predictive power and actual conditions. The external data sets were used to verify the predictive accuracy of the model. Results: All independent variables screened by Least Absolute Shrinkage and Selection Operator regression were independent risk factors for death in patients with severe heatstroke, which included neutrophil/lymphocyte ratio, platelet (PLT), troponin I, creatine kinase myocardial band, lactate dehydrogenase, human serum albumin, D-dimer, and APACHE-II scores. On days 10 and 30, the integrated discrimination improvement of the prediction model established was 0.311 and 0.364 times higher than that of the APACHE-II score, respectively; and the continuous Net Reclassification Index was 0.568 and 0.482 times higher than that of APACHE-II, respectively. Furthermore, we established that the area under the curve (AUC) of the prediction model was 0.905 and 0.918 on days 10 and 30, respectively. Decision curve analysis revealed that the AUC of this model was 7.67% and 10.67% on days 10 and 30, respectively. The calibration curve showed that the predicted conditions suitably fit the actual requirements. External data verification showed that the AUC on day 10 indicated by the prediction model was 0.908 (95% confidence interval, 82.2-99.4), and the AUC on day 30 was 0.930 (95% confidence interval, 0.860-0.999). Conclusion: The survival rate of patients with severe heatstroke within 24 h of admission on days 10 and 30 can be effectively predicted using a simple nomogram; additionally, this nomogram can be used to evaluate risks and make appropriate decisions in clinical settings.

Pharmacokinetics of tildipirosin in horses after intravenous and intramuscular administration and its potential muscle damage

Tildipirosin is a novel semisynthetic macrolide antibiotic exclusively used in veterinary practice to treat respiratory infections. There are no pharmacokinetic or safety information available regarding the use of tildipirosin after intramuscular administration in horses. Thus, the objective of this work was to determine the disposition kinetics of tildipirosin after intravenous (IV) and intramuscular (IM) administration in horses and its potential muscle damage and cardiotoxicity. Six mature, Spanish-breed horses were used in a crossover study with a washout period of 30 days. Tildipirosin (18%) was administered at single doses by IV (2 mg/kg) and IM (4 mg/kg) routes. Tildipirosin plasma concentrations were determined by HPLC assay with ultraviolet detection. Muscle damage and inflammation were assessed by creatine kinase (CK) and haptoglobin (Hp), respectively. Creatine kinase myocardial band (CK-MB) and troponin (Tn) were used to evaluate cardiotoxicity. Tildipirosin in horses reached peak concentrations (Cmax = 1.13 μg/mL) at 0.60 h (tmax) after IM administration with an absolute bioavailability of 109.2%. Steady-state volume of distribution and clearance were 3.31 ± 0.57 L/kg and 0.22 ± 0.02 L/h/kg, respectively. Tildipirosin did not cause cardiotoxicity since CK-MB and Tn basal levels were not significantly different from those obtained after several days post-administration. Mild local reactions were observed after IM administration. This local inflammation was associated with mild myolysis (CK 239–837 UI/L), which was detectable for 48 h. In brief, tildipirosin could help to treat respiratory infections in horses because it showed extensive distribution, high bioavailability and did not provoke general adverse reactions.

Risk factors of trauma-induced thrombotic microangiopathy-like syndrome: A retrospective analysis.

Patients with trauma may develop thrombocytopenia. We encountered cases wherein patients experienced symptoms resembling thrombotic microangiopathies (TMAs) following severe trauma. As the condition of these patients did not meet the diagnostic criteria of thrombotic thrombocytopenic purpura and there was no mention of trauma among the several causes of TMAs, it was termed as “trauma-induced thrombotic microangiopathy-like syndrome” (t-TMAS). In this study, we aimed to analyze the risk factors that may affect the incidence of t-TMAS in patients with severe trauma. This retrospective study was conducted in the trauma intensive care unit at the Kyungpook National University Hospital between January 2018 and December 2019. The medical records of 1164 of the 1392 enrolled participants were analyzed. To assess the risk factors of t-TMAS, we analyzed age, sex, mechanism of trauma, abbreviated injury scale (AIS) score, injury severity score (ISS), hematological examination, and red blood cell volume transfused in 24 hours. Among the 1164 patients, 20 (1.7%) were diagnosed with t-TMAS. The univariate analysis revealed higher age, ISS, and myoglobin, lactate, creatine kinase-myocardial band (on admission), creatine phosphokinase, lactate dehydrogenase (LDH), and lactate (day 2) levels in the t-TMAS group than in the non-t-TMAS group. The red blood cell volume transfused in 24 hours was higher in the t-TMAS group than in the non-t-TMAS group. t-TMAS was more common in patients with injuries in the chest, abdomen, and pelvis (AIS score ≥3) than in those with head injuries (AIS score ≥3) alone. The higher the sum of AIS scores of the chest, abdomen, and pelvis injuries, the higher the incidence of t-TMAS. Multivariate analysis revealed age, ISS, and LDH level (day 2) to be independent predictors of t-TMAS. Trauma surgeons should consider the possibility of t-TMAS if thrombocytopenia persists without any evidence of bleeding, particularly among older patients with multiple severe torso injuries who have high LDH levels on day 2. Early diagnosis and treatment of t-TMAS could improve patients’ prognosis.

Anti-Inflammatory Therapy for Acute Coronary Syndromes: Is It Time for a Shift in the Treatment Paradigm?

Anti-Inflammatory Therapy for Acute Coronary Syndromes: Is It Time for a Shift in the Treatment Paradigm?

Utility of routine laboratory tests in the assessment of chronic venous disease progression in female patients.

Chronic venous disease (CVD) is a frequently encountered disease that progresses with age. Although the principal method of evaluation and diagnosis is Doppler ultrasound, routine laboratory tests may be an easier and more accessible way to evaluate CVD progression. The present retrospective study evaluated the laboratory results of 256 patients diagnosed with CVD. According to the Clinical, Etiological, Anatomical and Pathophysiological classification, depending on the CVD stage, patients were stratified into three groups: Group 1 (C2-C3; mild disease), Group 2 (C4; moderate to severe disease) and Group 3 (C5-C6; severe disease). The considered parameters were age, red blood cell count (RBC), white blood cell count (WBC) and platelet count (PLT), percentage of neutrophils and lymphocytes, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, prothrombin time (in percentages and seconds), internal normalized ratio, activated partial thromboplastin time, creatine kinase (CK), CK myocardial band, alanine transaminase, aspartate transaminase, total bilirubin and urea. No significant differences among the groups were noted in RBC, WBC, PLT and coagulation factors; on the other hand, inflammatory markers exhibited differences among the groups. Several differences were observed in hepatic, metabolic and muscle tissue markers. Intraluminal thrombus formation in the case of varicose veins (thrombophlebitis) may be due to conditions of turbulent flow, stasis and endothelial inflammation, rather than hypercoagulability. The results of the present study confirmed the implication of inflammatory factors in pathophysiological modifications, including thickening of venous walls and valvular modification, as well as the appearance of intraluminal thrombi and trophic lesions. NLR, ESR, CRP and fibrinogen were increased with CVD progression and may be considered useful markers in evaluating CVD progression. Simple blood tests may provide phlebologists with additional insight for the management of those patients.

S-limonene protects the heart in an experimental model of myocardial infarction induced by isoproterenol: Possible involvement of mitochondrial reactive oxygen species

BackgroundMyocardial infarction (MI) is associated with high mortality rates, despite the fact that there are therapies available. Importantly, excessive oxidative stress may contribute to ischemia/reperfusion injury leading to death related to MI. In this scenario, naturally occurring antioxidant compounds are an important source of possible therapeutic intervention. Thus, this study sought to elucidate the mechanisms of cardioprotection of s-limonene in an isoproterenol-induced MI animal model. MethodsWistar rats were treated with 1 mg/kg s-limonene (SL) or 100 mg/kg N-acetylcysteine (NAC, positive control) once, 30 min after isoproterenol-induced MI (applied in two doses with a 24 h interval). The protective effects of SL in the heart were examined via the serum level of creatine kinase myocardial band (CK-MB), electrocardiographic profile, infarct size and histological parameters. Using isolated cardiomyocytes, we also assessed calcium transient amplitude, cytosolic and mitochondrial oxidative stress and the expression of proteins related to oxidative stress. ResultsSL at a concentration of 1 mg/kg attenuated isoproterenol-induced MI injury, by preventing ST-segment elevation and QTc prolongation in the ECG. SL reduced the infarct size and collagen content in cardiac tissue. At the cellular level, SL prevented increased Ca2+, associated with attenuation of cytosolic and mitochondrial oxidative stress. These changes resulted in a reduction of the oxidized form of Ca2+ Calmodulin-Dependent Kinase II (CaMKII) and restored superoxide dismutase and glutathione peroxidase activity. ConclusionOur data show that s-limonene promotes cardioprotection against MI injury, probably through inhibition of increased Ca2+ and attenuation of oxidative stress via CaMKII.

Combination of Sophora flavescens alkaloids and Panax quinquefolium saponins modulates different stages of experimental autoimmune myocarditis via the NF-κB and TGF-β1 pathways.

Chronic cardiac inflammation and fibrosis can progress into severe forms of cardiomyopathy. Sophora flavescens alkaloids (KuShen) have been previously reported to exert anti-inflammatory effects, whereas Panax quinquefolium saponins (XiYangShen) has been shown to alleviate cardiac fibrosis. Therefore, the potential effects of their combination (KX) on different stages of autoimmune myocarditis were investigated in the present study. Mice were randomly divided into the following four groups: Control; experimental autoimmune myocarditis (EAM); KX-High (275 mg/kg); and KX-Low (138 mg/kg). A 21-day and a 60-day EAM model was established through multi-site subcutaneous injections of cardiac myosin mixed with complete Freund's adjuvant on days 0, 7, 21 and 42. Mice in the High and Low KX groups were treated by gavage (10 ml/kg) daily from day 0 (1 day before treatment) until sacrifice (day 21 or 60). Mice in the control and EAM groups received an equivalent volume of distilled water. The levels of lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTn-I), IL-1β, IL-6, TNF-α, TGF-β1, collagen type I (Col Ⅰ) and collagen type III (Col Ⅲ) were measured by ELISA in the mouse myocardial tissues or serum. Myocardial tissue structure and extent of fibrosis were visualized using H&E and Masson's staining. Western blotting and immunohistochemistry were used to measure the expression levels NF-κB and TGF-β1 pathway proteins in the myocardial tissues. The degree of inflammation in the 21-day EAM model was found to be significantly higher compared with that in the 60-day EAM model. KX significantly reduced the inflammatory response at 21 days by decreasing the expression levels of CK-MB, LDH, cTn-I, IL-1β, IL-6, TNF-α and TGF-β-activated kinase 1-binding protein 1/NF-κB pathway proteins. Myocardial fibrosis in the 60-day EAM model was also significantly worse compared with that in the 21-day EAM model. However, fibrosis was significantly delayed by treatment with KX. In addition, KX significantly decreased the expression levels of TGF-β1, Smad2, Smad4, Col I and Col III. Therefore, these data suggest that KX is beneficial for treating myocarditis by targeting multiple pathways.

Cardiotoxicity of Chemical Substances: An Emerging Hazard Class.

(1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems. (2) Methods: To overcome the aforementioned gap, a roadmap is proposed for identifying regulatory criteria from animal studies and endorse legislation in order to classify substances as cardiotoxic. The roadmap consists of: (i) the identification of the appropriate animal species and strains; (ii) the identification of the lines of scientific evidence (e.g., histopathological, biochemical and echocardiographic indices etc.) from animal studies with relevance to humans; (iii) the statistical analysis and meta-analysis for each line of scientific evidence after exposure to well-established cardiotoxicants to humans (e.g., anthracyclines) in order to identify threshold values or range of normal and/ or altered values due to exposure; (iv) validation of the above described lines of evidence in animals exposed to other alleged cardiotoxic substances (e.g., anabolic androgen steroids (AAS) and pesticides); (v) establishment of mechanisms of action based on information of either known or alleged cardiotoxicants; and (vi) introduction of novel indices and in silico methods. (3) Results: Preliminary results in rats indicate a clear distinction from normal values to values measured in rats exposed to anthracyclines regarding left ventricle (LV) fractional shortening (FS) and LV ejection fraction (EF). A distinctive pattern is similarly observed for Creatine Kinase-Myocardial Band isoenzyme (CK-MB) and cardiac tissue glutathione (GSH). These findings are encouraging and indicate that there is room for targeted research to this end, and that these specific indices and biochemical markers should be further investigated in order to be developed to regulatory criteria. (4) Conclusions: Further research should be conducted by both the scientific and regulatory community that aims to clearly define the cardiotoxicity hazard caused by chemicals and develop a full set of scientific criteria.

Safety, Tolerability, and Effects of a Single Subcutaneous Administration of SP16 - a SERPIN-like, Small Peptide Agonist of the Low-Density Lipoprotein-like Receptor 1- on the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction.

Modulation of the inflammatory response is a promising therapeutic strategy in acute myocardial infarction. The novel approach is based on the anti-inflammatory and cytoprotective properties mediated by the engagement of the low-density lipoprotein‒related protein 1 (LRP1) receptor. SERPIN peptide 16 (SP16) is a synthetic, selective LRP1 agonist. We herein present the results of a study with a single subcutaneous administration of SP16 in 10 patients with STEMI, to appraise its safety and tolerability and explore the effects on the acute inflammatory response, infarct size, and cardiac function. Ten patients with ST-segment elevation myocardial infarction (STEMI) were enrolled within 12 hours of symptoms onset and 6 hours of percutaneous coronary intervention in a single-center, single-arm, open-label study of a single subcutaneous administration of SP16 (0.2 mg/kg). Serial clinical biomarkers and echocardiography data were collected up to 12 months. The data are presented separately for the treatment group and compared with historical controls from a placebo-treated arm in a recently completed clinical trial (N = 28) with similar enrollment criteria. All ten patients with STEMI received subcutaneous administration of SP16, 381 [272-478] minutes after percutaneous coronary intervention, without any treatment-related adverse events. The area under the curve for C-reactive protein was 133 [46-528] mg·d/L in the SP16-treated group versus 286 [141-581] mg·d/L in the historical placebo-treated group ( P = 0.161). The area under the curve for creatine kinase-myocardial band was 1432 [675-3089] ng·d/mL in the SP16-treated group versus 2367 [830-4750] ng·d/mL in the historical placebo-treated patients ( P = 0.428). Left ventricular ejection fraction was 46% [39-54] at baseline and 51% [46-58] at 1 year follow-up in SP16-treated patients (interval change 5% [-0.3% to +9%] P = 0.05) and 44% [38%-56%] at baseline and 53% [43%-59%] at 1 year follow-up in historical placebo-treated patients (interval change 3% [-5% to 10%], P = 0.305). A single subcutaneous administration of SP16, a synthetic targeted LRP1 agonist, was safe and well-tolerated in patients with STEMI. A trend toward reduction in the inflammatory response and infarct size with SP16 was noted; however, the sample size for this study was not based on formal statistical criteria. More extensive studies are planned to determine the clinical efficacy of SP16 in STEMI.NCT: NCT04225533.

Comparisons of High Intensity Interval Training and Continuous Training on Metabolomic Alteration and Cardiac Function in Male Adolescent Rats.

Background: Comparisons between high intensity interval training (HIIT) and continuous training (CT) regarding improvements of adolescents’ cardiac function are scarce and the preferred intensity for cardiac improvement with restricted myocardial damage remains unknown. This study conducted a 4-weeks training in male adolescent rats under moderate (MI) or high intensity (HI) HIIT and CT programs, aiming to discover and compare exercise-induced myocardial adaptations towards these two training methods. Methods: 39 male adolescent Sprague-Dawley rats (aged 4 weeks) were randomly assigned to high intensity HIIT (HI-HIIT, n = 8), moderate intensity HIIT (MI-HIIT, n = 8), high intensity CT (HI-CT, n = 8), moderate intensity CT (MI-CT, n = 8) and sedentary control (SC, n = 7) groups. Rats in training groups were trained for 4 weeks and echocardiography was performed at baseline and after the final training. Serum creatine kinase myocardial band (CK-MB), cardiac troponin T (cTn-T) and untargeted metabolomics analysis were measured from blood samples collected 24 h after the final training. Results: HIIT groups had greater cardiac output improvement than CT groups while no significant difference was found between the HI-HIIT and the MI-HIIT groups. HI-CT group showed higher serum CK-MB and cTn-T levels compared to MI-HIIT, MI-CT and control groups. Untargeted metabolomics analysis identified eleven HI-HIIT-related metabolites, five MI-HIIT-related metabolites and two HICT-related metabolites. The majority of the identified metabolites were phospholipid-related. Phosphatidylglyceride 18 level was significantly different between the HI-CT and MI-CT groups, and was negatively associated with cTn-T in CT groups. Conclusion: HIIT and CT improve cardiac function of adolescent rats while the HIIT demonstrates better improvement and less myocardial damage. High and moderate training intensities in HIIT exert similar cardiac benefits. HI-CT induced myocardial damage might be associated with serum phospholipids.