Cardiac Necrosis Research Articles

Effects of Long-term Anesthesia, Blood Sampling, Transportation, and Infection Status on Hearts and Brains in Pigs Inoculated with Staphylococcus aureus and Used for Imaging Studies.

Laboratory animals are widely used in imaging studies, including infection, heart, and brain research. Compared with rodents, pigs are especially useful because of their large organ sizes, ability to tolerate long-term anesthesia, and substantial blood volume, which allows repeated blood sampling. These factors are particularly important in positron emission tomography studies of potential new radioactive tracers, because the scans often are prolonged; in addition, kinetic studies involving repeated blood sampling may be performed to establish the optimal scan time. However, protracted studies may affect the cardiovascular system, brain, and other organs. This raises the question of how to monitor and counteract the effects of longterm anesthesia in pigs in a typical experimental setting yet prevent introducing bias into the experiment. To address this question, we investigated the effects of long-term anesthesia (maximum, 18 h), repeated blood sampling (maximum of 20 mL blood per kilogram body weight), and road transportation (as long as 1.5 h between 2 imaging centers) on key variables of lung, heart, and brain function in the context of a well-established pig model of Staphylococcus aureus infection. Pulse rate, oxygen saturation, body temperature, arterial pressure of CO₂, and urine production were stable during anesthesia for at least 16 h, whereas blood glucose slowly decreased. Hct and leukocyte count decreased due to repeated blood sampling. During road transportation, blood lactate levels increased 5 fold and arterial pressure of O₂ decreased by 50%. Repeated CT scans, necropsy results, and histopathology findings documented progressive lung changes and acute cardiac necrosis. No lesions indicative of hypoxia were found in brain. The study data show that the typical monitoring parameters do not fully depict the cardiovascular state of pigs during prolonged anesthesia. We recommend streamlining experimental protocols for imaging studies in pigs to avoid organ pathology.

Late Effects and Subsequent Neoplasms in Survivors of Adolescent and Young Adult Acute Lymphoblastic Leukemia: A Population-Based Analysis Including Impact of Front-Line Regimen Type

Background: Numerous studies have demonstrated superior survival for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-inspired as opposed to adult-type front-line ALL regimens. However, very little is known regarding the potential impact of therapeutic regimen type on late effects and subsequent neoplasms (SN) in AYA ALL survivors. Using population-based data, we describe associations between subsequent medical conditions/SN, sociodemographics, and ALL therapies, including regimen type (pediatric versus adult) in a large cohort of AYA ALL survivors. Methods: The California Cancer Registry (CCR) linked with California hospitalization data was used to evaluate socio-demographics, therapies, and subsequent medical conditions (late effects) amongst AYAs (15-39 years) diagnosed with ALL in California between 1995-2012 surviving a minimum of three years from diagnosis. The CCR was used to identify front-line therapeutic regimen, receipt of cranial irradiation (CRI), and SN; hematopoietic cell transplantation (HCT) and late effects were captured through hospitalization data. Late effects were categorized as cardiac (hypertensive disease, coronary artery disease, heart failure), neurologic (stroke, seizure), endocrine (thyroid disease, diabetes, ovarian/testicular dysfunction, other metabolic diseases), respiratory (asthma, chronic obstructive pulmonary disease, pulmonary fibrosis), renal (chronic kidney disease, hemodialysis, kidney transplant), liver (chronic liver disease, pancreatitis, cirrhosis, liver transplant), and avascular necrosis (AVN). The 10-year cumulative incidence (CMI) of developing each late effect/SN was estimated, accounting for death as a competing risk. Multivariable Cox proportional hazards regression analyses (MVA) examined the impact of sociodemographic factors and therapies (pediatric vs adult ALL regimen, HCT, CRI) on the occurrence of each late effect/SN. Front-line regimen type (pediatric vs adult) was highly correlated with receipt of HCT (P<0.001); thus, the impact of front-line regimen was evaluated in separate MVA for those who did and did not receive HCT. Results: Of the 1,069 survivors of AYA ALL (median follow-up, 8.2 years), 44% were 15-19 years at diagnosis, 32% were 20-29 years, 24% were 30-39 years; 62% were male and 50% were Hispanic. Thirty-nine percent resided in the lowest neighborhood socio-economic status (SES) tertile and 35% had public or no insurance. The majority (60%) received an adult-type front-line ALL regimen; 19% received CRI and 28% underwent HCT. Twenty-four SN occurred; thyroid, head and neck, and breast cancers were most common. The 10-year CMI of endocrine disease (29%) and cardiac disease (17%) were strikingly high; AVN (10%), respiratory disease (6%), liver disease (7%), seizure/stroke (4%), renal disease (3%) and SN (3%) occurred with descending incidence. Multivariable analyses including the entire patient cohort demonstrated that public or no insurance (vs private/military insurance) and receipt of HCT were independently associated with both late effects across organ systems and SN (Table 1A). Race/ethnicity, sex and neighborhood SES were not associated with late effects/SN. In MVA limited to the 766 AYAs who did not receive HCT, we continued to find a significant association between public and no insurance and all late effects, including SN. Front-line regimen type was not significantly associated with any of the late effect categories, nor was CRI (Table 1B). Among the 303 AYAs who received HCT, lower neighborhood SES was associated with higher risk of all late effects/SN considered. Conclusions: This large population-based analysis is amongst the first to describe late effects and SN in survivors of AYA ALL. Public or no health insurance and receipt of HCT were independently associated with the development of late effects across organ systems and SN, while front-line regimen type (adult vs. pediatric) among non-transplanted AYAs was not. The strong association between insurance type and late effects suggests that AYAs with public or no insurance may have reduced access to survivorship care following completion of ALL therapy. While additional follow-up is necessary to discern the full burden of late effects in survivors of AYA ALL, these findings suggest significant ongoing healthcare needs in this cancer survivor population. Disclosures Muffly: KITE: Consultancy; Pfizer: Consultancy; Adaptive: Research Funding.

Investigating the physiology of normothermic ex vivo heart perfusion in an isolated slaughterhouse porcine model used for device testing and training

BackgroundThe PhysioHeart™ is a mature acute platform, based isolated slaughterhouse hearts and able to validate cardiac devices and techniques in working mode. Despite perfusion, myocardial edema and time-dependent function degradation are reported. Therefore, monitoring several variables is necessary to identify which of these should be controlled to preserve the heart function. This study presents biochemical, electrophysiological and hemodynamic changes in the PhysioHeart™ to understand the pitfalls of ex vivo slaughterhouse heart hemoperfusion.MethodsSeven porcine hearts were harvested, arrested and revived using the PhysioHeart™. Cardiac output, SaO2, glucose and pH were maintained at physiological levels. Blood analyses were performed hourly and unipolar epicardial electrograms (UEG), pressures and flows were recorded to assess the physiological performance.ResultsNormal cardiac performance was attained in terms of mean cardiac output (5.1 ± 1.7 l/min) and pressures but deteriorated over time. Across the experiments, homeostasis was maintained for 171.4 ± 54 min, osmolarity and blood electrolytes increased significantly between 10 and 80%, heart weight increased by 144 ± 41 g, free fatty acids (− 60%), glucose and lactate diminished, ammonia increased by 273 ± 76% and myocardial necrosis and UEG alterations appeared and aggravated. Progressively deteriorating electrophysiological and hemodynamic functions can be explained by reperfusion injury, waste product intoxication (i.e. hyperammonemia), lack of essential nutrients, ion imbalances and cardiac necrosis as a consequence of hepatological and nephrological plasma clearance absence.ConclusionsThe PhysioHeart™ is an acute model, suitable for cardiac device and therapy assessment, which can precede conventional animal studies. However, observations indicate that ex vivo slaughterhouse hearts resemble cardiac physiology of deteriorating hearts in a multi-organ failure situation and signalize the need for plasma clearance during perfusion to attenuate time-dependent function degradation. The presented study therefore provides an in-dept understanding of the sources and reasons causing the cardiac function loss, as a first step for future effort to prolong cardiac perfusion in the PhysioHeart™. These findings could be also of potential interest for other cardiac platforms.

Regulating heart repair with cardiac-specific T lymphocytes.

Cardiac tissue necrosis secondary to coronary artery occlusion is one of the most common and deadly sterile injuries in developed countries. In this issue of the JCI, Rieckmann et al. identified and characterized antigen-specific CD4+ T helper (Th) cells that developed in the context of myocardial infarction (MI) in mice. They showed that myosin heavy chain α (MYHCA) is a dominant cardiac autoantigen and that T cells with T cell receptor (TCR) specificity to MYHCA acquired a Treg phenotype when adoptively transferred into infarcted mice, which mediated a cardioprotective healing response. Thus, Rieckmann et al. showed that an acute ischemic insult to the heart, which induces sterile inflammation, promoted, rather than limited, protective T cell autoimmunity. Notably, strategies that support an antigen-specific Treg response may limit the immune-inflammatory response and promote cardiac repair after acute MI.

Increased Complement Factor B and Bb Levels Are Associated with Mortality in Patients with Severe Aortic Stenosis

Inflammation is involved in initiation and progression of aortic stenosis (AS). However, the role of the complement system, a crucial component of innate immunity in AS, is unclear. We hypothesized that circulating levels of complement factor B (FB), an important component of the alternative pathway, are upregulated and could predict outcome in patients with severe symptomatic AS. Therefore, plasma levels of FB, Bb, and terminal complement complex were analyzed in three cohorts of patients with severe symptomatic AS and mild-to-moderate or severe asymptomatic AS (population 1, n = 123; population 2, n = 436; population 3, n = 61) and in healthy controls by enzyme immunoassays. Compared with controls, symptomatic AS patients had significantly elevated levels of FB (2.9- and 2.8-fold increase in population 1 and 2, respectively). FB levels in symptomatic and asymptomatic AS patients were comparable (population 2 and 3), and in asymptomatic patients FB correlated inversely with valve area. FB levels in population 1 and 2 correlated with terminal complement complex levels and measures of systemic inflammation (i.e., CRP), cardiac function (i.e., NT-proBNP), and cardiac necrosis (i.e., Troponin T). High FB levels were significantly associated with mortality also after adjusting for clinical and biochemical covariates (hazard ratio 1.37; p = 0.028, population 2). Plasma levels of the Bb fragment showed a similar pattern in relation to mortality. We concluded that elevated levels of FB and Bb are associated with adverse outcome in patients with symptomatic AS. Increased levels of FB in asymptomatic patients suggest the involvement of FB from the early phase of the disease.

Morphine alleviates myocardial ischemia/reperfusion injury in rats by inhibiting TLR4/NF-κB signaling pathway.

The aim of this study was to investigate the effect of morphine on myocardial ischemia/reperfusion (I/R) injury in rats and its underlying mechanism, thereby providing a reference for the prevention and treatment of myocardial I/R injury in clinical practice. A total of 60 male Sprague-Dawley (SD) rats were randomly divided into 3 groups, including: Sham group (n=20), I/R group (n=20) and I/R + morphine group (n=20) using a random number table. The left anterior descending coronary artery (LAD) of rat was ligated and re-canalized, and the I/R model was established in rats. Rats in I/R + sevoflurane (SEV) group were pretreated with 2.5% SEV. Infarction area of heart in each group was detected using triphenyltetrazolium chloride (TTC) test. Ejection fraction % (EF%) and fraction shortening % (FS%) were determined by echocardiography. Hematoxylin-eosin (HE) staining assay was performed to detect the morphological changes of cardiac myocardial cells in each group. Meanwhile, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining was adopted to detect the apoptosis of myocardial cells and fibroblasts. In addition, the expression levels of toll-like receptor 4 (TLR4) and p65 in heart samples of rats in each group were measured via immuno-histochemical staining. Finally, the influence of morphine on TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway was detected using Western blotting. Morphine significantly alleviated I/R-induced cardiac dysfunction in rats, whereas significantly increased EF% and FS% (p<0.05). In addition, morphine evidently inhibited myocardial infarction caused by I/R injury. Meanwhile, it reduced the infarction area from [(59.61±3.41) %] to [(26.67±3.62) %] (p<0.05). The results of HE staining showed that compared with I/R group, I/R + morphine group exhibited remarkably tidier cardiac myofilament, less degradation and necrosis, as well as significantly relieved cellular edema. Immuno-histochemical staining results revealed that morphine overtly reversed decreased expressions of TLR4 and p65 induced by I/R in rats (p<0.05). Furthermore, Western blotting found that morphine significantly inhibited the protein expressions of TLR4 and phosphorylated p65. Morphine clearly alleviates I/R-induced myocardial injury in rats. The possible mechanism may be associated with the inhibition on TLR4/NF-κB signaling pathway.

P3532Quantifying hemodynamic cardiac stress and cardiomyocyte injury in hypertensive and normotensive acute heart failure

Abstract Background Better characterization of the different pathophysiological mechanisms involved in normotensive and hypertensive acute heart failure (AHF) might help to develop novel individualized treatment strategies. Methods The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring B-type natriuretic peptide (BNP) as well as high-sensitive cardiac troponin T (hs-cTnT) in 1,152 unselected patients presenting with AHF to the emergency department (derivation cohort). Systolic blood pressure (SBP) of 90 - 140 mmHg at presentation was used to define normotensive AHF. Findings regarding hemodynamic cardiac stress and cardiomyocyte injury were validated in a second independent AHF cohort (validation cohort; n=324). Results In the derivation cohort 667 (58%) patients had hypertensive AHF. Hemodynamic cardiac stress, as quantified by BNP levels, was significantly higher in normotensive AHF as compared to hypertensive AHF (1,105 pg/mL versus 827 pg/mL, p&lt;0.001). In addition, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF (41 ng/L versus 33 ng/L, p&lt;0.001). These findings were confirmed in the validation cohort. Table 1. Cardiac stress and myocardial necrosis as quantified by BNP and hs-cTnT plasma concentrations Overall Hypertensive AHF Normotensive AHF p-value BNP in pg/ml, median (IQR) 974 (536–1,712) 827 (448–1,419) 1,105 (611–1,956) &lt;0.001 hs-cTnT in ng/L, median (IQR) 37 (22–67) 33 (19–59) 41 (24–71) &lt;0.001 BNP = B-type natriuretic peptide; hs-cTnT = high-sensitivity cardiac Troponin T; IQR = inter-quartile range. Figure 1 Conclusion Biomarker profiling revealed that the extent of hemodynamic stress and cardiomyocyte injury is different in patients with normotensive and hypertensive AHF. This characterization could help to understand AHF phenotypes better, which in turn may lead to more specific management in future, thus improving the dismal prognosis in these patients. Acknowledgement/Funding European Union, Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel

Increased serum microRNA‑21 levels reflect cardiac necrosis rather than plaque vulnerability in patients with acute coronary syndrome: a pilot study.

Increased serum microRNA‑21 levels reflect cardiac necrosis rather than plaque vulnerability in patients with acute coronary syndrome: a pilot study.

Cardioprotective effects of hesperidin on carbon monoxide poisoned in rats

Carbon monoxide (CO) poisoning causes cardiotoxicity and so far, no definite antidote has been proposed to overcome CO-induced adverse outcomes. Hesperidin, a citrus flavonoid, has shown cardio-protective effects in cardiac ischemia/reperfusion models. This study investigated the protective effects of hesperidin against CO-induced cardiac injury. To induce CO poisoning, rats were exposed to CO at 3000 ppm for 60 min. On the exposure day and the four following days, hesperidin (at three different doses of 25, 50, and 100 mg/kg/day) was administered intraperitoneally. A group of animals received normal saline and served as the control group. The electrocardiogram (ECG) was recorded and evaluated with special focus on S–T segment changes (depression or elevation), T-wave alterations, AV block and ventricular and supraventricular arrhythmias. On day 6 (i.e., the day after the last injection day), the animals were sacrificed and the hearts were harvested and evaluated for necrosis using hematoxylin and eosin staining. In addition, Akt protein expression levels and BAX/BCL2 ratio were determined by western blotting. Our results showed that hesperidin decreased cardiac necrosis. In animals treated with hesperidin 100 mg/kg, Akt protein expression was increased, while the BAX/BCL2 ratio was significantly decreased. ECG changes were reversed in all groups 2 h following CO exposure, regardless of hesperidin administration. Overall, hesperidin decreased the deleterious cardiac effects of CO poisoning in rats.

SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects.

Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the latest class of antidiabetic medication that inhibit the absorption of glucose from the proximal tubule of the kidney and hence cause glycosuria. Four SGLT2i are currently commercially available in many countries: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT2i reduce glycated hemoglobin by 0.5%–1.0% and have shown favorable effects on body weight, blood pressure, lipid profile, arterial stiffness and endothelial function. More importantly, SGLT2i have demonstrated impressive cardioprotective and renoprotective effects. The main mechanisms underlying their cardioprotective effects have been attributed to improvement in cardiac cell metabolism, improvement in ventricular loading conditions, inhibition of the Na+/H+ exchange in the myocardial cells, alteration in adipokines and cytokines production, as well as reduction of cardiac cells necrosis and cardiac fibrosis. The main adverse events of SGLT2i include urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Concerns have also been raised about the association of SGLT2i with lower limb amputations, Fournier gangrene, risk of bone fractures, female breast cancer, male bladder cancer, orthostatic hypotension, and acute kidney injury.

Study of biochemical markers in patients of ischemic heart disease and hypertension in IIMSR Hospital, Warudi

Introduction: Cardiovascular disease is the most frequent cause of adult death in industrial societies and is increasingly important in developing countries like India.In the year 2000 the European Society of Cardiology and the American College of Cardiology Committee jointly redefined Myocardial Infarction (MI) by an elevation of cardiology troponin T (Trop T) and cardiac troponin (cTn) is diagnostic and high sensitivity of cTn for detection of even small amounts of myocardial necrosis. Presently Troponin are the most prominent biomarker of cardiac injury is 1st cardiac biomarker which a clinician can use at the bedside of the patient for risk stratification of cardiac injury and have relegated conventional biomarkers like CK-MB to 2nd place. This is so because Cardiac Troponic are highly cardiac tissue specific unlike conventional biomarkers.Materials and Methods: Diagnosed ischemic heart disease (IHD) and hypertensive (HTN) patients were taken as cases, out of these divided into two groups of patients. The first group (n= 50) were patients with IHD including MI. The second group (n= 50) were patients with HTN and third group (n=50) were normal healthy control. In all 3 groups cTnT & CK-MB biochemical markers are evaluated.Results: In all diseased two groups cTnT and CK-MB biochemical markers are elevated and in control healthy group CTnT & CK-MB are normal.Conclusion: Small elevations of trop T identify minimal cardiac necrosis and patients can benefit from early invasive therapy. Trop T and CK-MB had an independent effect on long term survival and the combination of both is associated with even worse survival.

Protective role of polyphenolic compounds extracted from cyperus rotundus rhizomes and taurine on troponin-I and some oxidant/antioxidants parameters of female rats treated with isoproterenol – induced myocardial infraction.

The present study was designed to investigate the effects of polyphenolic compounds extracted from cyperus rotundus rhizomes and taurine on isoproterenol induced myocardial infraction in female rats. Sixty of female rats (Rattus norvegicus) were used in the present study. Animals were divided into 10 groups ( 6 for each group). MI was induced in rats with ISO (85 mg/kg) twice at an interval of 24 hrs. ISO produced significant alterations in the troponin-I, serum MDA, tissue MDA, Cp, Alb, uric acid, serum GSH and tissue GSH. The effect of polyphenolic compounds from cyperus rotundus rhizomes oral treatment for 21 days at two doses (15 mg and 30 mg/kg, body weight) and taurine at two doses ( 100 mg and 200 mg/kg, body weight) was evaluated against ISO- induced cardiac necrosis. The results showed a significant increase in the level of serum troponin-I, serum MDA, tissue MDA, Cp and uric acid in ISO- treated animals as compared with the control animals. While, the results showed asignificant decrease in the level of serum Alb, serum GSH and tissue GSH in ISO- treated animals as compared with the control animals. Polyphenolic compounds from cyperus rotundus rhizomes and taurine showed a significant cardioprotective activity by lowering the levels of serum troponin-I, serum MDA, tissue MDA, Cp and uric acid and elevate the levels of Alb, serum GSH and tissue GSH. This study concluded that the polyphenolic compounds from cyperus rotundus rhizomes and taurine possess cardioprotective activity against Isoproterenol induced myocardial infraction in rats.

THE DIAGNOSTIC VALUE OF TROPONIN I TESTING TO CORONARY ANGIOGRAPHY WITH A POINT OF CARE TESTING INSTRUMENT IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Myocardial infarction consists of STEMI and NSTEMI. Acute myocardial infarction is diagnosed by WHO criteria when at least two of the following three criteria are met: chest pain, electrocardiography (ECG) result changes, and biomarker. Troponin I is specific for cardiac muscle and has an increased level even in small cardiac muscle necrosis and not affected by the renal failure and muscle trauma but have not been standardized by WHO. This research aimed to find the effectivity of Troponin I examination with POCT to help the diagnosis and early detection of AMI. Thus each product has varied sensitivity and specificity. A cross-sectional study was conducted in the Clinical Pathology Laboratory and Cardiac Center of the Dr. Wahidin Sudirohusodo Hospital Makassar using suspected AMI patients as the subject. Troponin I level tested by POCT from August 2015 to July 2016. Data were analyzed statistically using the ROC curve with SPSS software. A total of 88 patients suspected with AMI, aged 36 to 75 years old. From the tested cut-off values (0.02, 0.03, 0.04, 0.5, 0.06, 0.07, 0.08 μg/L) the best cut-off value was 0.03 μg/L (93.9% sensitivity, 95.5% specificity, PPV 98.4%, NPV 84.0%, and 94.3% accuracy) where the cut-off value of 0.03 μg/L was the value recommended by the toolkit manual. Even if the cut-off value of 0.02 or 0.04 was used, the sensitivity and specificity value was still fairly good. Troponin I testing using POCT with a cut-off value of 0.03 μg/L can be used routinely in supporting the AMI diagnosis because it is a rapid test with a portable instrument and excellent diagnostic value.

Cardioprotective Actions of the Annexin-A1 N-Terminal Peptide, Ac2-26, Against Myocardial Infarction.

The anti-inflammatory, pro-resolving annexin-A1 protein acts as an endogenous brake against exaggerated cardiac necrosis, inflammation, and fibrosis following myocardial infarction (MI) in vivo. Little is known, however, regarding the cardioprotective actions of the N-terminal-derived peptide of annexin A1, Ac2-26, particularly beyond its anti-necrotic actions in the first few hours after an ischemic insult. In this study, we tested the hypothesis that exogenous Ac2-26 limits cardiac injury in vitro and in vivo. Firstly, we demonstrated that Ac2-26 limits cardiomyocyte death both in vitro and in mice subjected to ischemia-reperfusion (I-R) injury in vivo (Ac2-26, 1 mg/kg, i.v. just prior to post-ischemic reperfusion). Further, Ac2-26 (1 mg/kg i.v.) reduced cardiac inflammation (after 48 h reperfusion), as well as both cardiac fibrosis and apoptosis (after 7-days reperfusion). Lastly, we investigated whether Ac2-26 preserved cardiac function after MI. Ac2-26 (1 mg/kg/day s.c., osmotic pump) delayed early cardiac dysfunction 1 week post MI, but elicited no further improvement 4 weeks after MI. Taken together, our data demonstrate the first evidence that Ac2-26 not only preserves cardiomyocyte survival in vitro, but also offers cardioprotection beyond the first few hours after an ischemic insult in vivo. Annexin-A1 mimetics thus represent a potential new therapy to improve cardiac outcomes after MI.

Serum Highly Sensitive Cardiac Troponin I (hs-cTnI) as a Diagnostic Biomarker of Myocardial Injury after Pediatric Cardiac Catheterization

Background: new Highly Sensitive Cardiac Troponin I assay (as hs-cTnI) represents an important advance with added sensitivity for cardiac myocyte necrosis and could have several distinct roles in clinical practice. Aim of the present study: it was to determine the serum level of highly sensitive cardiac troponin I (hs-cTnI) before and after pediatric cardiac catheterization (diagnostic or interventional), as a diagnostic biomarker of myocardial injury in these patients. Patients and Methods: a Prospective Cohort study was carried out during the period from January 2017 to June 2018 at Pediatric Cardiology Unit and Cardiology Department, Tanta University Hospital. It included 30 patients who were admitted and required pediatric cardiac catheterization. Doppler echo- cardiography and Estimation of serum highly sensitive cardiac troponin I (hs-cTnI): using the ELFA technique (Enzyme Linked Fluorescent Assay) was done. Results: there was highly significant increase of serum hs-cTnI levels immediately after and 12 hours after therapeutic pediatric cardiac catheterization (p 0.05). There was significant negative correlation between serum hscTnI levels and Fractional shortening (FS) %, and also there was significant negative correlation between serum hs-cTnI levels and ejection fraction (EF) % (measured by echocardiography). Conclusion: serum highly sensitive cardiac troponin I (hs-cTnI) was significantly increased immediately after pediatric cardiac catheterization, with more significant increase after 12 hours, suggesting myocardial injury in these patients. Also, elevation of this diagnostic biomarker of myocardial injury was more after therapeutic than diagnostic pediatric cardiac catheterization.

Insights and challenges of indonesia’s acute coronary syndrome telecardiology network: three year experience from a single center and in west Jakarta, Indonesia

Acute Coronary Syndrome (ACS) is the leading cause of morbidity and mortality globally and in Indonesia. Reduce time to reperfusion is crucial in reducing cardiac myocardium necrosis and improving prognosis in ACS patients. The use of telecardiology shows great potential to bridge current inefficiencies and the Indonesian STEMI network (iSTEMI) was hence introduced in 2014. This study aims to provide insights and describe the challenges faced by Indonesia’s Acute Coronary Syndrome telecardiology network over the past 3 years based on a single center experience and in West Jakarta. Data was derived from the iSTEMI Network West Jakarta database obtained from the Department of Cardiology, Cengkareng General Hospital for the period of 30th June 2014 to 30th June 2017. The availability of the iSTEMI network in West Jakarta has made it more accessible for primary care facilities to receive direct consult and advice from cardiologists. Overall, over the three years patient ischemic time had reduced from a median of 330 minutes to 275 minutes. This study has shown great potential of pre-hospital telecardiology network in improving care in acute coronary syndrome patients by reducing ischemic time and hence improve patient’s chance of survival and recovery. A nationwide implementation of this system is therefore recommended to make better ACS care not only available to residents in Jakarta but to other parts of Indonesia as well.

FBXL10 regulates cardiac dysfunction in diabetic cardiomyopathy via the PKC β2 pathway

Diabetic cardiomyopathy (DCM) is a condition associated with significant structural changes including cardiac tissue necrosis, localized fibrosis, and cardiomyocyte hypertrophy. This study sought to assess whether and how FBXL10 can attenuate DCM using a rat streptozotocin (STZ)‐induced DCM model system. In the current study, we found that FBXL10 expression was significantly decreased in diabetic rat hearts. FBXL10 protected cells from high glucose (HG)‐induced inflammation, oxidative stress, and apoptosis in vitro. In addition, FBXL10 significantly activated PKC β2 signaling pathway in H9c2 cells and rat model. The cardiomyocyte‐specific overexpression of FBXL10 at 12 weeks after the initial STZ administration attenuated oxidative stress and inflammation, thereby reducing cardiomyocyte death and preserving cardiac function in these animals. Moreover, FBXL10 protected against DCM via activation of the PKC β2 pathway. In conclusion, FBXL has the therapeutic potential for the treatment of DCM.

Transthoracic echocardiography guided percutaneous laser ablation of the interventricular septum: A successful sheep model for septal thickness reduction and one year follow-up

BackgroundHypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease, causing breathlessness, chest pain, syncope and sudden death. One-year outcome of echo-guided transthoracic percutaneous laser ablation (TPLA) of the sheep interventricular septum was studied as a novel treatment to reduce the septal thickness. It may partially address the limitations of surgical myectomy and alcohol septal ablation in terms of trauma, safety, and efficacy. MethodsTwelve healthy adult sheep were randomly categorized into two groups: with and without the laser application of TPLA of the interventricular septum (IVS) at the energy level of 5 W for 3 min. Echocardiography, electrocardiography (ECG), cardiac magnetic resonance (CMR), serological and pathological examinations were performed over a 12-month follow-up. ResultsAfter the laser ablation all animals survived with normal cardiac function; No severe complications or bundle branch block were noted. The septal thickness (3.11 ± 1.14 vs. 8.40 ± 0.45 mm, p < 0.05), regional movement of ablated IVS and longitudinal strain significantly decreased when comparing the experimental and control groups. The Troponin I level was significantly elevated after the operation, which validated immediate cardiac coagulation necrosis. On cardiac magnetic resonance (CMR) imaging, the ablated myocardium showed significant fibrosis evidenced by late gadolinium enhancement. Pathological results revealed damaged ultra-structure of the ablated myocardium and development of fibrosis. ConclusionsTPLA is a safe and effective minimally invasive method to reduce IVS thickness in the long term, making it a potential alternative for HOCM treatment.

Preclinical Pharmacological Profiling and Cardioprotective Activity for Methanolic Extracts of Stem Bark of Muntingia calabura L against Adrenaline Induced Cardio-Toxicity

Medicinal plants have been a major antecedent for treatment of human diseases since time immemorial. The present study was designed to perform the preclinical pharmacological profile and evaluation of the cardioprotective activity of methanolic extracts obtained from stem bark of Muntingia calabura L. Wistar albino rats (n=6) were used for acute and sub acute toxicity study. The control groups received vehicle (2ml/kg, p.o.) and the other groups administered from 100 to 2000 mg/kg, per oral (p.o) of the methanolic extract of M. calabura bark. In sub-acute toxicity studies control group recieved vehicle (3ml/kg, p.o.) and other recieved 500 mg/kg p.o. of methanolic extracts of M. calabura L stem bark. Rats (n = 6) were treated with methanolic extracts of stem bark of M.calabura L of 50mg/kg and 100mg/kg for 30 days and one with Propranolol for last 7 days, one as toxic control. The treated groups were subjected to Adrenaline (2mg/kg, s.c.) toxicity on 31St day. Effects were evaluated after 24hrs treatment were investigated for changes of electrocardiographic (ECG) parameters, serum biomarkers, tissue antioxidants, lipid profile, and histopathological examination. Tissue and Serum homogenate parameters were analysed by spectrophotometer and semi-auto analyzer respectively. Results obtained were assessed by the one-way analysis of variance with Tukey–Karmer multiple comparison test. In acute and sub-acute toxicity studies animals were observed continuously from 4 hours to 14 days for observation of behavioral changes, The hematological, histopathological and biochemical parameters were analysed for safe preclinical pharmacological profile of methanolic extracts of stem bark of M.calabura L. The best effective group of methanolic extracts of stem bark of M.calabura L is 100mg/kg which showed extremely significant (P < 0.001) decrease in serum biomarker levels and produced profound decrease of cardiac necrosis compared to toxic control group and found subtled cardioprotection.

Effect of metoprolol in a chronic murine model of cardiotoxicity induced by doxorubicin and trastuzumab

Trastuzumab (anti ErbB2 targeted therapy) and anthracyclin can lead to a synergistic cardiotoxicity with a severe decrease of cardiac function. To date, a cardioprotective treatment is not recommended in all patients. Our objective was to define whether metoprolol (β1blocker) used as a cardioprotective treatment was efficient to prevent signs of chronic cardiotoxicity induced by doxorubicin and trastuzumab. Males C57B8l6 mice ( n = 60) were injected during 2 weeks with intraperitoneal (IP) doxorubicin (total dose: 24 mg/kg) or saline, and then with IP trastuzumab (total dose of 10 mg/kg) or saline for 2 more weeks. Half of mice received metoprolol (100 mg/kg) in drinking water 10 days before starting protocol and during all the study (42 days). A functional exploration was carried out by transthoracic echocardiography. Biological analysis included quantification of plasma troponin I, cardiac transcript using RT-qPCR, signaling pathways using Western Blotting and immunohistology. We observed an excess of mortality in the metroprolol group (22% vs. 7%, P < 0.05). Metoprolol did not prevent the decrease of cardiac function assessed by shortening fraction (SF): 41% and 39% in the chemotherapy groups with and without metoprolol, respectively. Metoprolol did not protect mice from heart failure assessed by an increase of BNP and a decrease of SERCA2a. Mice treated with doxorubicin developped a cardiac atrophy. Metoprolol did not modify the cardiomyocyte atrophy (assessed by cardiomyocyte size), the excess of cardiac apoptosis (assessed by caspase 3 activity) nor the cardiac necrosis (assessed by troponin I) all induced by chemotherapies. Albeit previous work suggested a cross-regulation between ErbB2 and β adrenergic signaling pathway, our data indicated that metoprolol used as cardioprotective treatment, did not protect heart from toxicity induced by doxorubicin and trastuzumab.