Serum Creatine Kinase-myocardial Band Research Articles

Pravastatin attenuates isoprenaline induced cardiac fibrosis in a mouse model

ABSTRACT We investigated the effects of pravastatin (PRAVA) on isoprenaline (ISP) induced cardiac fibrosis using four groups of mice: untreated control, PRAVA, ISP, ISP + PRAVA groups. ISP, 20 mg/kg, was administered subcutaneously daily for 14 days. PRAVA, 20 mg/kg, was administered orally daily for 14 days. Mice were sacrificed on day15 and heart and blood samples were collected to investigate cardiac injury markers. The mean body weight for the ISP group on day 15 was decreased significantly compared to day 0; PRAVA increased the mean body weight slightly on day 15 of treatment compared to day 0. The heart:body weight ratio was increased in the ISP group compared to the control group, but the ratio was returned to near control ratio in the PRAVA + ISP group. The serum creatine kinase-myocardial band (CK-MB) level was reduced significantly in the PRAVA + ISP group compared to the ISP group. Serum triglyceride level was decreased significantly in ISP + PRAVA group compared to the ISP group. PRAVA administration significantly reduced tissue collagen I and III levels in the ISP + PRAVA group compared to the ISP group. Lipid oxidation was decreased and reduced glutathione activity was increased in the PRAVA + ISP group compared to the ISP group. IL-6, α-SMA, CTGF, TGF-β and SMAD-3 gene expressions were decreased in the PRAVA + ISP group compared to the ISP group. We found fewer inflammatory cells and less fibrosis in heart tissue in the PRAVA + ISP group compared to the ISP group. PRAVA decreased ISP induced cardiac fibrosis by reducing oxidative stress, collagen deposition and inflammation, as well as by decreasing expression of TGF-β, SMAD-3 and CTGF genes.

Evaluation of the effect of oxidative stress on dynamics of cardiac biomarkers in Georgian elite athletes with overtraining syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Training of professional athletes comprises of repetitive overloading to initiate structural and functional changes for favorable adaptation to the workouts, but with an inadequate recovery overloading may produce non-functional overreaching(NFO) and then overtraining syndrome(OTS). It is important to study chronic effects of exercises via responses of biomarkers for understanding of muscle fatigue and cardiac damage to identify athletes at risk of poor adaptation to training[3,4]. The purpose was to study the effects of oxidative stress on dynamics of cardiac biomarkers in Georgian elite athletes with OTS. Methods On the initial stage in 43 athletes(37 with NFO, 6 with OTS) study of relationship between oxidative stress and OTS revealed imbalance between oxidant production and antioxidant protection via attenuation of antioxidant capacity in athletes with OTS[1,2]. On the current stage of our study,in 43 NFO/OTS athletes and 40 age-matched controls without NFO/OTS pre-season serum creatine kinase myocardial band(CK-MB) and cardiac troponin I(cTnI) were measured, followed by in-season evaluation of the dynamic of their changes(HUMAN,Germany). In-season levels of CK-MB and cTnI were obtained 24hrs before strenuous sport-specific exercise of peak-season intensity, immediately after the work-load,after 6, 48,and 72hrs. Baseline and post-execise clinical assessment and transthoracic echocardiography(TTE) were performed in 6 and 48hrs after strenuous session(6 hrs corresponds to the time when cTnI is typically detectable in ischemic models;48 hrs-CK concentrations recovery time). Results Similar rising trend of CK-MB and cTnI levels was observed immediately after exercise, reaching peak values after 6hrs in all athletes, though, significantly greater in NFO/OTS athletes than in controls, and slightly exceeded reference range of cTnI (in NFO 0.128±0.092ng/ml, in OTS 0.137±0.061ng/ml). After 48hrs of recovery CK-MB and cTnI in NFO/OTS athletes were significantly higher than on entry, showing slower recovery,though normalized in 72hrs. TTE didn’t reveal any sustained alterations of systolic and diastolic functions, or clinically threatening myocardial damage, only minor diastolic changes due to adaptation to the post-exercise haemodynamic in OTS athletes(E/A pre-exercise:1.47±0.25, post-exercise:in 6hrs 1.06±0.14,in 48hrs 1.40±0.09,p<0,05). Elevated cardiac markers after strenuous exercise can be linked to increased cellular permeability and cardiac troponin leakage, amplified by oxidative stress existent in OTS athletes. Conclusions In our study intensive exercise caused transient increase of the CK-MB and cTnI in NFO/OTS athletes, without irreversible pathophysiological and clinical consequences, suggesting mostly benign cardiac involvement, though amplified by existent oxidative stress in athletes with OTS. Monitoring responses via alterations of biochemical parameters can be helpful to guide athletic training and prevent OTS.

A combination of Sophoraflavescens alkaloids and Panaxquinquefolium saponins attenuates coxsackievirus B3‑induced acute myocarditis in mice via NF‑κB signaling.

Timely treatment of viral myocarditis (VMC), a form of cardiac inflammation caused by viral infections, can reduce the occurrence of dilated cardiomyopathy and sudden death. Our previous study demonstrated the anti-inflammatory and anti-fibrotic effects of KX, a combination of Sophora flavescens alkaloids and Panax quinquefolium saponins, on an autoimmune myocarditis model in vivo. The present study explored the effects of KX on coxsackievirus B3 (CVB3)-induced acute VMC in mice. Mice were randomly divided into four groups: Control, VMC, KX-high (275 mg/kg) and KX-low (138 mg/kg). Mice in the VMC, KX-high and KX-low groups received injections of CVB3 to establish the VMC model, and those in the KX-high and KX-low groups also received KX by gavage (10 ml/kg) 2 h after virus injection until euthanasia was performed on day 7 or 21. Mice in the control group received an equal KX volume of purified water. The levels of lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTn-I), IL-1β, IL-6, TNF-α and high-sensitive C-reactive protein (hs-CRP) in mouse serum was measured using ELISA. Myocardial tissue structure and degree of injury were observed using hematoxylin and eosin staining. Western blotting and reverse transcription-quantitative PCR were performed to detect the expression levels of NF-κB pathway-related mRNA and protein in myocardial tissue. The results showed that the inflammation and myocardial damage levels of the mice in the VMC group were higher at 7 days than those at 21 days. At both 7 and 21 days, KX decreased the serum CK-MB, LDH, cTn-I, IL-6, TNF-α and hs-CRP levels, and inhibited NF-κB pathway-related mRNA and protein expression in the myocardium of mice. These findings indicated that KX may reduce the inflammatory response and attenuate the pathological damage in the acute and subacute phases of CVB3-induced VMC through the NF-κB pathway.

Baicalein prevents capecitabine-induced heart damage in female Wistar rats and enhances its anticancer potential in MCF-7 breast cancer cells

AimWe investigated the ability of baicalein (BAI) to enhance the anticancer potential of capecitabine (CAP) in the MCF-7 cell line and its protective effect on CAP-induced cardiotoxicity in female Wistar rats. Methods and key findingsIn vitro study involved evaluating the effect of BAI and/or CAP on cell viability, cell cycle progression, and BAX and Bcl2 gene expression in MCF-7 cells. Co-treatment of BAI with CAP significantly reduced the viability of MCF-7 cells, improved their cytotoxic effect, markedly elevated the percentage of the sub-G1 population, drastically reduced the G2/M population, and significantly altered the mRNA expression of BAX and Bcl2 genes compared with each treatment alone. In vivo study revealed that the oral administration of CAP (140 mg/kg BW) to adult female rats significantly elevated the levels of serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β and cardiac TNF-α, IL-1β malondialdehyde (MDA) concentration, whereas it reduced the serum and cardiac total antioxidant capacity (TAC), level of cardiac glutathione (GSH) and activity of glutathione peroxidase (GPx) with a vast array of circulatory, inflammatory, degenerative, and necrotic alterations in the cardiac tissue. Furthermore, CAP administration significantly upregulated the mRNA expression of NF-κB, TLR4, MyD88, ATF6, CHOP, and JNK genes. Concurrent administration of BAI (200 mg/kg BW) and CAP significantly improved the biochemical alterations and cardiac oxidant/antioxidant status and architecture. In addition, it modulated the TLR4/MyD88/NF-κB pathway and endoplasmic reticulum stress. SignificanceAltogether, BAI can augment the anticancer potential of CAP and alleviate its cardiotoxic effects during cancer treatment.

Effects of carvacrol on ketamine-induced cardiac injury in rats: an experimental study

Aim We aimed to investigate the preventive effects of carvacrol against ketamine-induced cardiotoxicity biochemically and histopathologically in an experimental model. Material and method The rats were divided into three groups; healthy control (HC), ketamine alone (KG), and ketamine + carvacrol (KCG) groups. Serum Creatine Kinase Myocardial Band (CK-MB) and Troponin I (TP I) levels were determined. Malondialdehyde (MDA), Glutathione (GSH), Superoxide Dismutase (SOD), Tumor Necrosis Factor α (TNF-α), Interleukin 1 beta (IL-1beta), and Interleukin 6 (IL-6) levels were measured in the heart tissues of the rats. Heart tissues were also evaluated histopathologically. Results In the ketamine-treated group, tissue MDA, TNF-α, IL-1beta, and IL-6 levels increased while tissue GSH and SOD levels decreased significantly compared with the control group. However, in the ketamine plus carvacrol applied group, all those alterations were significantly less pronounced, close to the healthy controls. Severe mononuclear cell infiltrations, degenerated myocytes and hemorrhage were determined in the ketamine alone administered group, and these alterations were at a mild level in the carvacrol + ketamine administered group. Conclusion Prolonged exposure to ketamine resulted in induced oxidative stress in rat heart tissue; concomitant carvacrol application could counteract the negative effects of ketamine by protecting tissues from lipid peroxidation and decreasing the inflammatory response.

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.

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.

Juglanin alleviates myocardial injury in rats with acute myocardial infarction through modulating MAPK signaling pathway

The aim of this study was to investigate the protective role of Juglanin in rats suffering from acute myocardial infarction (AMI). Male Sprague–Dawley (SD) mice were used to construct the AMI model. Hematoxylin and Eosin staining was used to observe the morphological changes of cardiomyocytes. Changes in lactate dehydrogenase (LDH), caspase-3 and caspase-9 were measured using commercial kits. Enzyme-linked immunosorbent assay was used to measure the serum level of creatine kinase myocardial band (CK-MB), Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-10 and IL-1β. Protein expression and phosphorylation were determined by Western blotting test. The morphology of cardiomyocytes suffered great changes because of AMI, which included focal myocardial necrosis, severe inflammatory cell infiltration, and myocardial fiber dissolution, disorder, and partial rupture. The morphological changes in cardiomyocytes were significantly ameliorated through treatment with Juglanin (10 mg/kg and 30 mg/kg). Increment of serum CK-MB, LDH, IL-6, TNF-α, IL-10 and IL-1β was reduced in AMI rats treated with 10-mg/kg and 30-mg/kg Juglanin. Cell apoptosis was also inhibited by Juglanin treatment. AMI-induced phosphorylation of p38, extracellular signal-regulated kinase (p-ERK) and c-Jun N-terminal kinase (p-JNK) was suppressed through treatment with Juglanin. This study demonstrated that Juglanin alleviated myocardial injury in rats because of AMI through inactivation of mitogen-activated protein kinase signaling pathway, thus indicating a protective role in rat AMI model.

Association of peri-procedural myocardial infarction with mortality after stenting true coronary bifurcation lesions: A pooled individual participant data analysis from four randomized controlled trials.

Five definitions of peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) are used in clinical trials; their clinical relevance in coronary bifurcation stenting remains unclear. To understand the correlation between PMI and mortality in bifurcation lesions from the DKCRUSH studies. PMI was defined using serum creatine kinase-myocardial band (CK-MB) values within 48 h of PCI according to the SYNTAX, Fourth Universal Definition of MI (4th UDMI), ISCHEMIA, SCAI, and EXCEL definitions. Overall, 1300 patients with both CK and CK-MB measurements pre- and post-stenting were evaluated. The association of each PMI type and all-cause death or cardiac death at a median of 5.58 years of follow-up was analyzed using Cox regression. In total, 56 (4.3%) patients had PMI. According to SYNTAX, 4th UDMI or ISCHEMIA, SCAI, and EXCEL definitions, PMI occurred in 21 (1.6%), 56 (4.3%), 29 (2.2%), and 32 (2.5%) patients, respectively. All definitions were significantly correlated with unadjusted mortality at the end of follow-up but not at 30 days or 1-year after stenting. PMI using SYNTAX, SCAI, and EXCEL definitions rather than 4th UDMI definition was strongly associated with adjusted all-cause death. By adjusted analysis, PMI according to 4th UDMI, SCAI, and EXCEL definitions but not SYNTAX definition was positively correlated with cardiac death at a median of 5.58 years of follow-up. CK-MB ≥ 5 x UNL strongly enhanced the correlation of CK-MB values with mortality. PMI rate varies with the definition following stenting for bifurcation lesions. PMI defined by SCAI and EXCEL definitions is strongly correlates with adjusted all-cause and cardiac death.

Effect of different cardioprotective methods on extracorporeal circulation in fetal sheep: a randomized controlled trial

BackgroundCongenital heart disease is a leading cause of death in newborns and infants. The feasibility of fetal cardiac surgery is linked to extracorporeal circulation (ECC); therefore, cardioplegic solutions need to be effective and long-lasting.MethodsEighteen pregnant sheep were divided into an ECC-only group, St. Thomas’ Hospital cardioplegic solution (STH1) group (STH group), and HTK preservation solution (Custodiol®) group (HTK group). Markers of myocardial injury including troponin I (cTnI), troponin T (cTnT) and creatine kinase myocardial band (CKMB) were measured at specific time points (T1: pre-ECC, T2: 30 min of ECC, T3: 60 min of ECC, T4: 60 min post-ECC, T5: 120 min post-ECC). Myocardial tissue was removed from the fetal sheep at T5, and apoptosis was detected by TUNEL staining.ResultsChanges in the serum cTnI, cTnT and CKMB concentrations were not significantly different among the three groups before and during the ECC(T1,T2,T3). At 60 min after ECC shutdown(T4), cTnI and cTnT concentrations were significantly higher in the STH group than before the start of ECC. The concentration of cTnI was higher in the STH group than in the HTK and ECC-only groups. The concentration of cTnT was higher in the STH group than in the ECC-only group. At 120 min after ECC shutdown(T5), cTnI and cTnT concentrations were significantly higher in the ECC and HTK groups than before the start of ECC, and CKMB concentration was significantly higher in STH and HTK groups. The concentrations of cTnT, cTnI and CKMB was higher in the STH group than in the HTK and ECC-only groups. The number of TUNEL-positive cells in the HTK and STH groups was higher than in the ECC-only group. The number of TUNEL-positive cells in the STH group was higher than in the HTK group. There was no statistically significant difference among the groups in the heart rate and mean arterial pressure after ECC.ConclusionThe HTK preservation solution was significantly better than STH1 in reducing the release of cardiomyocyte injury markers and the number of apoptotic cells in fetal sheep ECC. Fetal sheep receiving ECC-only had an advantage in all indicators, which suggests ECC-only fetal heart surgery is feasible.

Efficacy of Trimetazidine in Limiting Periprocedural Myocardial Injury in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

We systematically searched the literature to assess the efficacy of trimetazidine in reducing periprocedural myocardial injury and improving postoperative left ventricular ejection fraction (LVEF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). An electronic search was conducted based on the PubMed, Ovid, Scopus, Springer, CENTRAL, and Google Scholar databases; 14 randomized controlled trials (RCTs) were included. Our meta-analysis showed a significant reduction in cardiac troponin I (cTnI) levels with trimetazidine compared with controls (P < .00001) but not in serum creatine kinase-myocardial band levels (P = .49). There were significantly reduced odds of ischemic ST-T segment changes with trimetazidine (P = .0.03) but lack of significant difference in the incidence of anginal attacks between the 2 groups (P = .10). Results also suggest significantly higher LVEF with trimetazidine compared with controls (P < .00001). Meta-regression analysis indicated no influence of duration of trimetazidine therapy on cTnI levels. The administration of preprocedure trimetazidine may have a role in reducing periprocedural myocardial injury in patients with CAD undergoing PCI. Evidence also suggests that postoperative trimetazidine may improve LVEF in the short term. Lack of high-quality trials and the heterogeneity of studies limit the ability of our analysis to draw strong conclusions. Further well-designed RCTs are required to supplement current evidence.

Cardiac amyloidosis mimicking acute coronary syndrome: a case report and literature review.

BackgroundCardiac amyloidosis, a progressive cardiac disease, results from the accumulation of undegraded proteinaceous substrates in the extracellular matrix of the heart. It may present as acute coronary syndrome (ACS); therefore, a clear distinction remains challenging in clinical practice. We describe a case of cardiac amyloidosis mimicking ACS.Case summaryA 72-year-old man experienced chest discomfort for 2 days. He gradually developed dyspnoea during the preceding month. Electrocardiogram (ECG) showed sinus rhythm with right bundle branch block and low voltage. Echocardiography revealed concentric left ventricular thickening, biatrial dilation, and preserved ejection fraction with predominantly left ventricular basal hypokinesis. Serial testing of the cardiac biomarkers showed persistently increased high-sensitive cardiac troponin T levels and normal serum creatine kinase myocardial band levels. He was diagnosed with ACS with haemodynamic stability. However, coronary angiography demonstrated non-obstructive coronary arteries. Furthermore, significant macroglossia and periorbital purpura were noticed. Laboratory investigations revealed elevated serum immunoglobulin free light chain (FLC) kappa and lambda levels with an increased FLC ratio. Histological analysis of the biopsied abdominal skin confirmed amyloidosis.DiscussionCardiac amyloidosis often presents as restrictive cardiomyopathy. The usual symptoms include dyspnoea and peripheral oedema. Chest pain may manifest rarely, leading to misdiagnosis as coronary artery disease. Some findings suggestive of cardiac amyloidosis include clinical signs such as amyloid deposits, dyspnoea, low ECG voltage, and basal-predominant hypokinesis with relative apical sparing in echocardiography. Serum FLC test and abdominal skin biopsy can confirm the diagnosis of amyloidosis when a myocardial biopsy is not feasible.

Ibudilast, a Phosphodiesterase Inhibitor and Toll-Like Receptor-4 Antagonist, Improves Hemorrhagic Shock and Reperfusion-Induced Left Ventricular Dysfunction by Reducing Myocardial Tumor Necrosis Factor α

ObjectivesRapid loss of blood volume causes ischemic injury to myocardial cells and impairs cardiac function. Subsequent reperfusion, although necessary to revitalize stunned tissues, can induce production of reactive oxygen species and inflammation, causing further tissue damages and weakening cardiac function. Ibudilast, a Toll-like receptor-4 (TLR4) antagonist and an inhibitor of phosphodiesterase-4, possesses antioxidative and anti-inflammatory capacities. In this study, we aim to examine the protective efficacy of ibudilast against hemorrhagic shock and reperfusion (HSR)-induced myocardial injury and cardiac dysfunction. MethodsStudies were conducted on male Sprague-Dawley rats in 3 groups: sham-operated, HSR with, and HSR without pretreatment of ibudilast. Hemorrhagic shock was induced by withdrawing blood from the femoral artery until the mean aortic pressure dropped to around 40 mm Hg; reperfusion was conducted by replenishing blood after 120 minutes of hemorrhagic shock, and the observation continued for another 240 minutes. The left ventricular (LV) contractility, diastolic suction capacity, and ventricular stiffness were evaluated using simultaneous LV pressure, and volume was recorded during a temporary inferior vena cava constriction at the end of reperfusion. Ibudilast (10 mg/kg) was administered intraperitoneally 3 days and 20 minutes prior to HSR. Serum creatine kinase myocardial band (CK-MB) was examined at the end of both HSR, and serum CK-MB, myocardial TLR4 protein expression, and malondialdehyde (MDA) and tumor necrosis factor (TNF)-α levels at the end of reperfusion. ResultsHSR induced an increase in serum CK-MB. Subsequent reperfusion further increased serum CK-MB, upregulated myocardial TLR4 protein expression, and increased tissue levels MDA and TNF-α vs the sham (P < .05). HSR reduced LV contractility, prolonged LV relaxation time, and increased LV diastolic stiffness. Ibudilast pretreatment attenuated HSR-induced TLR4 protein expression, reduced myocardial MDA and TNF-α levels, and protected against cardiac dysfunction. ConclusionsIbudilast pretreatment reduced myocardial TLR4 expression, decreased MDA and TNF-α levels, and protected against HSR-induced decrease in LV contractility, prolonged LV relaxation time, and increased diastolic stiffness.

Predictive Role of Cardiac Troponin I, Creatine Kinase-Mb and Electrocardiogram in Early Assessment of Acute Cardiotoxicity in Patients Poisoned by Cardiotoxic Drugs and Toxins

Background: In spite speedy development of clinical toxicology researches and protocols cardiovascular failure in severe acute intoxication remains a leading cause of death. Early cardiovascular risk assessment in acutely intoxicated patients is a must nowadays.&#x0D; This study aims to evaluate the role of ECG, serum cardiac troponin I (cTnI) and creatine kinase myocardial band (CK-MB) for early detection of cardio-toxicity in acutely poisoned patients.&#x0D; Methods: Prospective study was carried on100 patients with acute cardiotoxicity by drugs and toxins known to cause cardiac injury admitted to Sohag University hospitals, informed written consent has been obtained from each patient; ECG and biochemical analysis of serum cTnI and CK-MB were estimated in all studied patients.&#x0D; Results: (90%) of studied patients had complete free recovery, (4%) discharged with complications and (6%) of patients died. ECG test can be used as a predictor of mortality and had sensitivity 100%, specificity 46.8% and negative predictive value (NPV) 100%. Serum cTnI was highly significantly increased with death hence could be used as predictors of outcome. While serum CK-MB couldn't be used as an outcome predictor. ROC curve analysis to assess serum cTnI as a predictor of mortality of acute cardiovascular toxicity with cut off &gt; 1.0 ng/ml had sensitivity 100%, specificity 89.4% and NPV 100% with excellent diagnostic characteristic (accuracy rate 96.4%). There is no significant difference of serum CK-MB and serum cTnI among cardiac drugs toxicity patients and non-cardiac toxins patients.&#x0D; Conclusion: the study concluded that ECG and serum cTnI can be used as a predictor of mortality. Also, the protocol of management will be same in acute cardiotoxicity by cardiac drugs and non-cardiac drugs and toxins.&#x0D; Recommendation: the study recommends combining of ECG changes and serum cTnI as they can early detect acute cardiovascular effects in acutely poisoned patients.

Electroacupuncture preconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated by the mTORC1-ULK1-FUNDC1 pathway

Myocardial ischemia/reperfusion (I/R) is an important complication of reperfusion therapy for myocardial infarction, and trimetazidine is used successfully for treatment of ischemic cardiomyopathy by regulating mitochondrial function. Moreover, electroacupuncture (EA) preconditioning was demonstrated to be cardioprotective in both in vivo rodent models and in patients undergoing heart valve replacement surgery. However, the mechanisms have not been well elucidated. Mitophagy, mediated by the mTORC1-ULK1-FUNDC1 (mTOR complex 1-unc-51-like autophagy-activating kinase 1-FUN14 domain-containing 1) pathway, can regulate mitochondrial mass and cell survival effectively to restrain the development of myocardial ischemia/reperfusion injury (MIRI). In this study, we hypothesized that EA preconditioning ameliorated MIRI via mitophagy. To test this, rapamycin, an mTOR inhibitor, was used. The results showed that EA preconditioning could reduce the infarct size and risk size, and decrease the ventricular arrhythmia score and serum creatine kinase-myocardial band isoenzyme (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTnT) in MIRI rats. Moreover, it also attenuated MIRI-induced apoptosis and mitophagy accompanied by elevated mTORC1 level and decreased ULK1 and FUNDC1 levels. However, these effects of EA preconditioning were blocked by rapamycin, which aggravated MIRI, reduced adenosine triphosphate (ATP) production, and antagonized infarct size reduction. In conclusion, our results indicated that EA preconditioning protected the myocardium against I/R injury by inhibiting mitophagy mediated by the mTORC1-ULK1-FUNDC1 pathway.

Performance of Copeptin for Early Diagnosis of Acute Myocardial Infarction in an Emergency Department Setting.

BackgroundRapid and accurate diagnosis of acute myocardial infarction (AMI) is critical for initiating effective treatment and achieving better prognosis. We investigated the performance of copeptin for early diagnosis of AMI, in comparison with creatine kinase myocardial band (CK-MB) and troponin I (TnI).MethodsWe prospectively enrolled 271 patients presenting with chest pain (within six hours of onset), suggestive of acute coronary syndrome, at an emergency department (ED). Serum CK-MB, TnI, and copeptin levels were measured. The diagnostic performance of CK-MB, TnI, and copeptin, alone and in combination, for AMI was assessed by ROC curve analysis by comparing the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value of each marker were obtained, and the characteristics of each marker were analyzed.ResultsThe patients were diagnosed as having ST elevation myocardial infarction (STEMI; N=43), non-ST elevation myocardial infarction (NSTEMI; N=25), unstable angina (N=78), or other diseases (N=125). AUC comparisons showed copeptin had significantly better diagnostic performance than TnI in patients with chest pain within two hours of onset (AMI: P=0.022, ≤1 hour; STEMI: P=0.017, ≤1 hour and P=0.010, ≤2 hours). In addition, TnI and copeptin in combination exhibited significantly better diagnostic performance than CK-MB plus TnI in AMI and STEMI patients.ConclusionsThe combination of TnI and copeptin improves AMI diagnostic performance in patients with early-onset chest pain in an ED setting.

Septal reduction therapy using nonalcohol agent in hypertrophic obstructive cardiomyopathy: Single center experience.

Percutaneous septal reduction therapy by either alcohol or nonalcohol agents is an alternative approach to surgery in drug-refractory symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). Nonalcohol agents have some advantages and disadvantages over alcohol during the procedure. Nowadays, a novel non-alcohol agent, named as Ethylene-vinyl alcohol (EVOH) copolymer (Onyx® and Squid® ), is used during septal ablation. Thus, in this study, we aimed to evaluate both acute and long-term efficacy and safety profile of EVOH during septal ablation in HOCM. A total of 25 patients (52% female; mean age: 55.8 ± 17.1 years) with symptomatic HOCM were enrolled in the study. All subjects underwent clinical and laboratory assessment before and after the procedure. Peak left ventricular outflow tract (LVOT) gradient was significantly reduced just after the procedure (68 vs. 20 mmHg; P < 0.001). Peak serum creatine kinase-myocardial band and troponin I levels were 112 (35-282) ng/ml and 11 (4-93) ng/ml. EVOH embolization to diagonal artery was observed in 1 patient (4%) and the complete atrioventricular block was noted in 2 (8%) patients. During the 12-month follow-up, there was no mortality. There was a significant improvement in New York Heart Association functional class of the subjects P < 0.001). Both interventricular septum thickness and LVOT gradient showed a significant reduction during follow-up (P < 0.05). However, there was no reduction in the LVOT gradient of 3 patients (12%). In conclusion, our small-sized preliminary study results showed that septal reduction therapy using EVOH is an effective alternative option in reducing symptoms and LVOT gradient in HOCM.

Kudiezi injection mitigates myocardial injury induced by acute cerebral ischemia in rats

BackgroundKudiezi (KDZ) injection is commonly used in traditional Chinese medicine as treatment for cerebral infarction and angina pectoris. The present study investigated the therapeutic effects of KDZ injection on myocardial injury induced by acute cerebral ischemia and the possibly protective mechanisms.MethodsRats were divided into three groups: sham, 6h-ischemia, and KDZ treatment (KDZ). The neurological deficits were determined by the Garcia score. The cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content was also evaluated. Serum creatinine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) activity, myocardial tissue malondialdehyde (MDA) levels, L-Glutathione (GSH) levels, and superoxide dismutase (SOD) activity as well as mitochondrial cytochrome c oxidase (COX) activity were determined. Mitochondrial COX I and COX III mRNA expressions of myocardial tissues were measured by RT-PCR.ResultsImpaired neurological function and brain edema were observed in the 6h-ischemia group. TTC staining showed that the 6h-ischemia group had larger infarct zones than the sham group. Myocardial ischemic changes (widened myocardial cell gap, cracks, and obvious edema) were detected in the 6h-ischemia group compared with the sham group, with elevated serum CK-MB activity and CK and LDH levels. Electrocardiography showed lower medium frequency (MF) and high frequency (HF) in the 6h-ischemia group compared with the sham group. In myocardial tissue, COX activity was elevated in the 6h-ischemia compared with the sham group, while SOD, GSH, and MDA levels, and COX I and COX III mRNA expressions remained unchanged. KDZ injection decreased neurological impairment, brain edema, gaps between cells, and infarct size. Compared with the 6h-ischemia group, it reduced serum CK-MB activity and CK and LDH levels, and MDA levels in myocardial tissue. KDZ significantly increased GSH levels, SOD activity, and mitochondria COX activity and the expression of COX I and COX III mRNA in myocardial tissue compared with the sham group.ConclusionKDZ injection had a protective effect against cerebral ischemia in rats. KDZ injection could also alleviate myocardial injury after acute cerebral ischemia in rats. The possible mechanisms involve the regulation of the oxidative stress/antioxidant capacity after cerebral ischemia.

Protective effects of kolaviron and gallic acid against cobalt-chloride-induced cardiorenal dysfunction via suppression of oxidative stress and activation of the ERK signaling pathway.

Cobalt (Co) toxicity is a potential public health problem due to recent renewed use of Co in orthopedic implants, dietary supplements, and blood doping in athletes and horses. We investigated the protective roles of kolaviron (KV), a bi-flavonoid of Garcinia kola, and gallic acid (GA) on cobalt chloride (CoCl2)-induced cardiorenal damage in rats. CoCl2 caused significant increases (p < 0.05) in serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), xanthine oxidase (XO), urea, creatinine, malondialdehyde, H2O2, nitric oxide, as well as C-reactive protein expression, along with significant (p < 0.05) reduction in cardiac and renal expression of extracellular signal regulated kinase (ERK) and the activities of superoxide dismutase, catalase, and glutathione S-transferase. KV and GA prevented the toxic effects of CoCl2 by stimulating ERK expression and reversing Co-induced biochemical changes. Administration of CoCl2 alone did not significantly alter ECG patterns in the rats, although co-treatment with KV (200 mg/kg) produced QT-segment prolongation and also appeared to potentiate Co hypotension. Histopathology of the heart and kidneys of rats treated with KV and GA confirmed the biochemical data. KV and GA thus protected against cardiac and renal damage in Co intoxication via antioxidant and (or) cell survival mechanisms, possibly involving ERK activation.

Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models.

The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice.