Myocardial Destruction Research Articles

Protective Effect of Prunetin on Isoproterenol-Induced Myocardial Infarction in Wistar Rats via Biochemical Characterization.

The development of MI following ischemia damage is influenced by oxidative stress. Myocardial Infarction (MI) generates myocardial ischemia injury, which damages the cardiomyocytes. Ischemia builds up to a critical level over time in MI, causing permanent myocardial cell damage or death. The current study sought to determine whether Prunetin (PRU) could protect against Isoproterenol (ISO)-induced cardiac heart failure in rats by examining cardiac diagnostic markers, lipid peroxidation products, enzymatic and non-enzymatic antioxidant levels, and histological changes. PRU (20 mg/kg bwt) was orally administered for 19 days to rats, and after the treatment, ISO (85 mg/kg bwt) was subcutaneously administered with an intermission of 24 h for a couple of days to induce myocardial infarction on 20th and 21st days. ISO-treated rats exhibited considerable alterations in cardiac-sensitive markers in the serum. The levels of lipid peroxidation markers augmented drastically in the plasma and myocardium. Enzymatic antioxidant levels in erythrocytes and myocardium and the states of non-enzymatic antioxidants were diminished in the plasma and heart tissue of ISO-treated rats. The histopathological examination of heart tissue exhibited cardiac damage in ISO-induced rats. The oral administration of PRU significantly lowered the levels of lipid peroxidation and biochemical indicators, while significantly improving the antioxidant system function of ISO-interposed rats. In PRU-treated ISO-injected rats, histological examinations revealed suppressed myocardial destruction. Our research shows that oral pretreatment of PRU prevented ISO-induced oxidative stress in MI.

The effectiveness of computer assisted programme on knowledge and practice regarding immediate care of patients with myocardial infarction among staff nurses

Myocardial destruction was observed but not modified by the cardiologist. It has become increasingly clear that to make a real impact on the prognosis of patients with myocardial infarction. The goal of medical management is to minimize myocardial damage, preserve myocardial function, and prevent complications. the researcher felt the need to assess the effectiveness of computer assisted programme on knowledge & Practice Regarding immediate care of patient with myocardial infarction among staff nurses in admitted in selected wards of Jawaharlal Nehru Hospital & Research centre sector -9 Bhilai C.G.The purpose of experimental study was to study, observe and explore the cause and effect relationship of a situation. In this study the design used in Quasi Experimental one group pre-test and post test research design. The setting for present study is Jawaharlal Nehru Hospital & Research Centre Sector -9 Bhilai C.G. In this study a total of 30 samples for assessment of knowledge & practice of Jawaharlal Nehru Hospital & Research Centre Sector -9 Bhilai C.G. Non- Probability Purposive Sampling technique was used for selecting the sample.The comparison of knowledge score between pre test & post test in which 20%(6) subjects were in Average , 76.67%(26) subjects were in Good, 3.33%(1) subjects were in Excellent pre test knowledge score regarding immediate care of myocardial infarction patient. In Post test knowledge level the majority of staff nurse’s 46.67% (14) subjects in Excellent knowledge level & 53.33% (16) were in Good knowledge regarding immediate care of myocardial infarction patients. Pre test Mean Knowledge score was 10.53, Mean % was 43.88%, S.D of pre test knowledge score was 2.9 & CV was 27.54 & post test Mean knowledge score was 16.54, Mean % was 68.33%, S.D of post test knowledge score was 2.95 & C.V of post test was 17.99. The Practice score of Pre test Mean was 12, mean % was 50% with S.D 1.88 & C.V was 15.67 & Post test practice Mean score was 19.87, mean % was 82.79 with S.D 2.34 & C.V was 11.78.Prevalence of acute myocardial infarction as the first manifestation of ischemic heart disease is high, approximately 50%. Hypertensive individuals more frequently have symptoms preceding acute myocardial infarction, probably due to ventricular hypertrophy associated with high blood pressure levels.

CA-533-02 STANDARD CARDIAC RADIOABLATION DOSE (25 GRAY) DOES NOT CAUSE MYOCYTE INJURY OR NEW FIBROSIS

Noninvasive cardiac radioablation (CRA) is an emerging therapy for refractory ventricular tachycardia (VT). Focused radiation to the heart is expected to cause local myocardial destruction with replacement fibrosis (ablation effect). The extent this effect in humans is unknown. To measure the CRA ablation effect with serial serum biomarkers and late gadolinium enhanced cardiac MRI (LGE-CMR). Single-center, IRB-approved case series of patients with refractory VT (ENCORE-VT NCT02919618). Patients without contraindication underwent LGE-CMR and blood draws at three timepoints: before treatment, 3 days, and 3 months after treatment. Left ventricle (LV) scar burden was assessed using semi-automatic contouring (Medis, Netherlands), blinded to location of radioablation. Global and segmental scar burden (%) was compared across timepoints. Segments targeted for radioablation (25 Gray) were compared to surrounding and off-target segments. Blood samples were analyzed for high-sensitivity troponin-I (Tn-I, marker of myocyte injury) and galectin-3 (Gal3, marker of fibroblast activation and fibrosis). 7 patients were included for analysis: mean age 64 years, 14% female, 57% nonischemic cardiomyopathy, 86% with history of VT storm, mean LVEF 32% (range 19-58%). Mean number of cardiac segments targeted for radioablation was 4 (range 3-8), resulting in mean cardiac treatment volume (CTV) 29 cm3 and planning treatment volume (PTV) 114 cm3. Mean scar burden at baseline was 49% (range 29-68%). Changes in scar burden at 3 days and 3 months were -0.4% (IQR = 5.5%) and 3.3% (IQR = 3%). Segment-by-segment analysis (Figure 1) showed no significant scar progression in segments targeted for radioablation (mean 68% to 68% to 71%), segments surrounding the target (43% to 44% to 47%), or off-target segments (44% to 42% to 46%). Serum Tn-I and Gal3 were not significantly changed (Figure 2). Compared to VT burden before treatment, all 7 patients had substantial reduction 6 months after treatment (4 had > 95% burden reduction, 1 had resolution of incessant slow VT). Despite improvement in VT burden, there was no appreciable cardiac injury or replacement fibrosis after CRA with 25 Gray. The mechanism of early VT control with cardiac radioablation is not myocyte injury or fibrosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

High-sensitivity cardiac troponin and C-reactive protein dynamics after cardiac electrophysiological procedures

The catheter ablation of cardiac arrhythmias causes myocardial destruction and increase of the cardiac troponin and C-reactive protein (CRP). Data regarding dynamics of high-sensitivity troponin during irrigated ablation are scarce, and for diagnostic electrophysiological studies (EPS) are lacking. We aimed to study the periprocedural dynamics of high-sensitivity cardiac troponin I (hscTn I) and CRP, as well as their relation to different procedural parameters during EPS and ablation of various arrhythmias. Material and methods: Consecutive patients with EPS or ablation performed were studied prospectively. Clinical and procedural characteristics, and pre- and postprocedural values of hscTn I and CRP are presented at days 1, 2 and 3. Six indices were chosen as procedural markers of induced myocardial injury. P-value < 0.05 was accepted as statistically signifi cant for all tests performed. Results: Eight EPS and 98 ablations were performed in 103 patients (58 males, 56.3%). For ablations the baseline values of hscTn I at day 1 were 3.2 ng/L (1.7-4.93), while postprocedural values at days 2 and 3 were 500 ng/L (269-1044) and 404 ng/L (179-1017), р < 0.05 for all days. Postprocedural hscTn I values were moderately to strongly correlated to radiofrequency (RF) energy, time and number of RF applications. Postprocedural increase of CRP was also significant, but its magnitude was much smaller. Its correlation to procedural indices was weak. For EPS the baseline values of hscTn I were 5.95 ± 5.34 ng/L (0.6-15.9), while for the next 2 days these were 53.2 ± 43.1 ng/L (13.3-144) и 16.7 ± 9.65 ng/L (3.3-30.9), р < 0.05 for all days. Conclusion: Signifi cant postprocedural increase of hscTn I was detected in all electrophysiology procedures – EPS and ablations. This increase was more pronounced and prolonged to at least the next day after ablation. It was clearly correlated to the cumulative RF energy, RF time and number of RF applications. Early increase of CRP was also signifi cant, but to a lesser magnitude and in weak correlation to the procedural parameters.

Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients

IntroductionHeart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence shows that active digestive enzymes can leak out of the small intestine into the systemic circulation and cause cell dysfunctions and organ failure.MethodsAccordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion.ResultsWestern analysis shows that trypsin in plasma is significantly elevated in HF compared to matched controls and their concentrations correlate with the cardiac dysfunction biomarker BNP and inflammatory biomarkers CRP and TNF-α. The plasma trypsin levels in HF are accompanied by elevated pancreatic lipase concentrations. The trypsin has a significantly elevated activity as determined by substrate cleavage. Mass spectrometry shows that the number of plasma proteins in the HF patients is similar to controls while the number of peptides was increased about 20% in HF patients. The peptides are derived from extracellular and intracellular protein sources and exhibit cleavage sites by trypsin as well as other degrading proteases (data are available via ProteomeXchange with identifier PXD026332).ConnclusionsThese results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients.ConclusionsThese results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients.

Evaluation of changes in instrumental and biochemical markers of heart diseases in patients with bladder cancer under the condition of intravenous and intravesical doxorubicin administration

Due to the constant increase in morbidity and mortality, bladder cancer remains a pressing problem in modern medicine. Despite the success of chemotherapy, chemotherapy physicians around the world have been concerned about the safety of these drugs for many years. Doxorubicin has been used as an antitumor drug for more than 40 years in various hematological and solid malignancies, however, its toxic effects when administered intravenously to vital organs and organ systems, including the heart, require further research. The aim of our study was to evaluate the manifestations and progression of cardiotoxicity in patients with bladder cancer with systemic and intravesical administration of doxorubicin. The study included 96 patients who were divided into three groups: the first group or the control group – patients who had a confirmed diagnosis of first stage bladder cancer, were treated surgically and did not receive doxorubicin; the second group – patients who, in addition to surgical treatment, received doxorubicin systemically (intravenously) in a therapeutic dose; the third group – patients who received doxorubicin at a dose of 50 mg, locally, by instillation of the drug into the bladder cavity, after prior catheterization with an elastic catheter. ECG data and biochemical markers of myocardial destruction before and after chemotherapy were studied. The study found that systemic serial administration of doxorubicin to patients with bladder cancer causes significant changes in the myocardium after the first course of chemotherapy. A single intravesical instillation of doxorubicin does not cause changes in laboratory and instrumental heart rate.

P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy

Abstract Background Non-ischemic dilated cardiomyopathy (niDCM) is a common debilitating disease leading to heart failure and poor prognosis. Therefore, a reliable diagnosis of niDCM and search of prognostic biomarkers is a task of paramount importance preventing final destruction of myocardium and improving the outcomes of the disease. The aim of the study was to evaluate the prognostic value of carboxy-terminal telopeptide (ICTP), a marker of myocardial collagen I degradation, and Caspase-3, a marker of apoptosis, in serum and endomyocardium biopsies (EMBs) of patients with niDCM. Methods 34 consecutive patients (male 25 (78%); 43.83±12.17 years) with niDCM (average of left ventricle (LV) end-diastolic diameter 6.94±0.78 cm, LV ejection fraction 24.97±6.93%, mean pulmonary capillary wedge pressure 32.9±8.7 mmHg) were enrolled in the study. The levels of ICTP and Caspase-3 in patients' serum and EMBs were measured by ELISA. After a follow-up period of 5 years, 18 patients (53%) have reached the primary composite end-point of heart failure: 6 patients (17.6%) died, 6 patients (17.6%) had heart transplantation and 6 patients (17.6%) underwent left ventricle assist device implantation. Results Univariate Cox proportional hazard model and ROC curve analysis identified levels of ICTP and Caspase-3 in serum as predictors of composite end-point (Table 1). However, the levels of ICTP and Caspase-3 in EMBs had no prognostic value. The cut-off values of serum biomarkers for prediction of the outcome were 13.43 pg/mg protein (sensitivity 67%; specificity 81%) for ICTP and 10.21 pg/mg protein (sensitivity 53%; specificity 87%) for Caspase-3. Univariate Cox regression analysis revealed that patients with higher levels of ICTP and Caspase-3 than cut-off values in serum had higher risk of reaching the composite end-point compared to the patients with lower cut-off values (HR 4.4 (95% CI: 1.6–12.1) and 3.15 (95% CI: 1.2–8.29), respectively). Kaplan-Meier survival analysis demonstrated that patients with serum Caspase-3 and ICTP levels above cut-off values had significantly worse outcome (p=0.01 and p=0.002, respectively). Table 1 Biomarkers (pg/mg protein) Mean ± SD HR (95% CI) p-value AUC (95% CI) ICTP in serum 15.26±10.59 1.052 (1.013–1.093) 0.009 0.71 (0.53–0.89) ICTP in EMB 132±295 0.999 (0.998–1.001) 0.56 0.45 (0.28–0.61) Caspase-3 in serum 7.78±9.86 1.047 (1.002–1.093) 0.04 0.69 (0.51–0.87) Caspase-3 in EMB 283±282 1 (0.998–1.002) 0.92 0.50 (0.28–0.72) Conclusion The findings show that increased serum levels of Caspase-3 and ICTP are significantly associated with poor outcome in patients with niDCM. Acknowledgement/Funding the Research Council of Lithuania (Grants nos. MIP-086/2012 and MIP-011/2014), the European Union, EU-FP7, SARCOSI Project (no. 291834)

P951The factors influencing total ischaemic time in patients presenting with STEMI in an Irish tertiary referral centre

Abstract Background Despite highly functioning primary percutaneous coronary intervention (PPCI) programmes, STEMI is still associated with significant morbidity and mortality. The European Society of Cardiology STEMI guidelines in 2017 introduced a novel metric relating to STEMI patients: “total ischaemic time”. This time-period starts at the onset of chest pain and ends at wire cross, and it is thought to accurately reflect burden of myocardial destruction. Aims To assess the total ischaemic time of patients presenting with STEMI in an Irish tertiary referral centre and the factors influencing delays in presentation and treatment. Methods Prospective cohort analysis was conducted on all patients presenting with STEMI from October 2017 to January 2019. Patients were included if they had a culprit lesion that was successfully revascularized. All information was recorded at time of presentation. Bayesian statistics were employed to conduct the analysis. Results 158 patients were recruited. Mean age was 61 (range29–96). Male:female ratio 5:1 in this cohort. Average total ischaemic time was 409.4mins ±501.4. The average time from chest pain to “call for help” (i.e. patient delay) was 208.3mins ±397.8, which represented 50.89% of the total ischaemic time (see Figure 1). The average time from “call for help” to first medical contact (FMC) was 18.4mins ±30.07. Average time from FMC to ECG was 44.9mins ±151.16, and was dependent upon type of FMC (Primary care 127mins vs paramedic 25mins p=0.030932). After FMC, 48.7% of patients had an ECG performed in under 10mins as per guidelines. After ECG was performed, 46.4% of patients had ECG to “wire cross” time under 90mins as per guidelines; 65.8% were within 120 mins and 91.4% were within 180mins. Those presenting to their general practitioner as FMC were significantly less likely to have both an ECG <10mins (NNH 2.84 95% CI 1.79–6.91) and ECG to wire time of <90mins (NNH 6.13 95% CI 2.88–48.70). As age increased, so too did total ischaemic time (Pearson R=0.164, p=0.043), which was dependent on increasing patient delay with age (Pearson R=0.2181, p=0.0066). Women had a higher total ischaemic time than men (546 vs 382mins p=0.0233). This was determined to be as a result of: a numerically higher patient delay (220 vs 206 mins, p=0.214) and women having a longer time from FMC to ECG (104mins vs 34mins, p=0.0021). Conclusion Over 50% of the total ischaemic time was due to patient delay, suggesting a role for cardiovascular awareness programmes. Increasing age was associated with longer patient delay, indicating a need for directed awareness in this demographic. Women had a higher total ischaemic time, and waited a significantly longer time for ECG following FMC; highlighting the need for awareness amongst healthcare professionals of atypical clinical features associated with STEMI in women. Patients who attended their GP waited longer for an ECG and, once performed, were less likely to be revascularised within 90mins.

Molecular mechanisms of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy is a genetic disorder characterized by the risk of life-threatening arrhythmias, myocardial dysfunction and fibrofatty replacement of myocardial tissue. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of arrhythmogenic cardiomyopathy and can be identified in about half of patients with the condition. However, the molecular mechanisms leading to myocardial destruction, remodelling and arrhythmic predisposition remain poorly understood. Through the development of animal, induced pluripotent stem cell and other models of disease, advances in our understanding of the pathogenic mechanisms of arrhythmogenic cardiomyopathy over the past decade have brought several signalling pathways into focus. These pathways include canonical and non-canonical WNT signalling, the Hippo-Yes-associated protein (YAP) pathway and transforming growth factor-β signalling. These studies have begun to identify potential therapeutic targets whose modulation has shown promise in preclinical models. In this Review, we summarize and discuss the reported molecular mechanisms underlying the pathogenesis of arrhythmogenic cardiomyopathy.

Acute coronary syndrome : Prevention

For life style modifications primary and secondary prevention of acute coronary syndrome (ACS) are approximately similar, even though in the postinfarction situation functional diagnostic programs have to be performed in arehabilitative manner. All three life style pillars of fitness, nutrition and relaxation implicate prognostic significance and the efficacy is higher for secondary prevention than for primary. The pharmacotherapeutic indications for thrombocyte aggregation inhibition are connected to the presence of atherosclerosis and statin medication is already connected to cardiovascular risk factor stratification, for which scores are used. Depending on the postinfarction myocardial destruction after ACS, additional pharmacotherapies, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, beta blockers and also mineral corticoid receptor antagonists are evident. New potential for prevention is ascribed to the new oral anticoagulants (NOAC) in the context of coincidental atrial fibrillation.

The immunoproteasome controls the availability of the cardioprotective pattern recognition molecule Pentraxin3

Cardiomyocyte death as a result of viral infection is an excellent model for dissecting the inflammatory stress response that occurs in heart tissue. We reported earlier that a specific proteasome isoform, the immunoproteasome, prevents exacerbation of coxsackievirus B3 (CVB3)-induced myocardial destruction and preserves cell vitality in heart tissue inflammation. Following the aim to decipher molecular targets of immunoproteasome-dependent proteolysis, we investigated the function and regulation of the soluble PRR Pentraxin3 (PTX3). We show that the ablation of PTX3 in mice aggravated CVB3-triggered inflammatory injury of heart tissue, without having any significant effect on viral titers. Thus, there might be a role of PTX3 in preventing damage-associated molecular pattern-induced cell death. We found that the catalytic activity of the immunoproteasome subunit LMP7 regulates the timely availability of factors controlling PTX3 production. We report on immunoproteasome-dependent alteration of ERK1/2 and p38MAPKs, which were both found to be involved in PTX3 expression control. Our finding of a cardioprotective function of immunoproteasome-dependent PTX3 expression revealed a crucial mechanism of the stress-induced damage response in myocardial inflammation. In addition to antigen presentation and cytokine production, proteolysis by the immunoproteasome can also regulate the innate immune response during viral infection.

Possible role of complement factors and their inhibitors in the myocardial infarction: an immunohistochemical study.

Ongoing development of our civilization is accompanied by a marked increase of incidence of cardiovascular diseases and cardiovascular mortality. Ischemic heart disease with its extreme form – myocardial infarction – is one of the main problems of modern medicine. Despite much research devoted to this disease entity, its pathomechanism remains incompletely understood. Basing on research reports, more and more emphasis is put on immune reactions in the myocardium. Available literature lacks detailed studies examining the role of complement system and its inhibitors in the development and pathogenesis of myocardial infarction. Cells of ischemic myocardium were proven to become foreign antigens for the immune system of the patient's body. This results in complement activation of formation of so called membrane attacking complex that injures myocardial cells. By binding to its surface, it extends the myocardial destruction caused by the infarction itself.Results of immunochemistry studies presented in this paper have demonstrated the existence colocalization of complement components (C4d, C9) and membrane inhibitors (CD55, CD59) as well as soluble inhibitors (factor H) of the complement in the examined muscle tissue that underwent ischemic necrosis. Positive immunohistochemical reaction was found in the myocardial cells, intercellular matrix and blood vessels.

ERACEing the Risk of Cerebral Embolism From Atrial Fibrillation Ablation

Atrial fibrillation (AF) is the most common arrhythmia requiring treatment. The adverse outcomes commonly attributed to AF include symptomatic palpitations, dyspnea and exertional intolerance, and increased risk of thromboembolic complications, especially stroke. Because of the morbidity of this condition, several different treatment strategies have been derived to improve patient outcome. One of the strategies that are being used increasingly is catheter ablation. Presently, this is an aggressive, extensive ablation procedure designed to isolate triggering foci from electric conduction to the body of the atria and modifying atrial substrate to disrupt or prevent conduction/propagation of reentrant wave fronts. This procedure can be of long duration and associated with extensive myocardial destruction. Most of the ablation is performed in the systemic circulation. Because of these factors, systemic embolic events, especially stroke, have always been feared complications associated with this procedure.1 Although the prevalence of stroke complications has been low, concern has been raised in recent years about the observation of asymptomatic cerebral embolism (ACE) on diffusion-weighted MRI.2–4 Article see p 835 ACE lesions after catheter ablation of AF were first reported by Lickfett et al5 and since have been described by several groups. The mechanisms leading to the formation of ACE lesions have not been completely elucidated but are presumed to be because of microembolism to the small terminal intracerebral arteries.1 The components of the microembolic material causing ACE lesions after AF catheter ablation are hypothesized to be thrombus, gas microbubbles, heat-denatured albumin microbubbles, thermal coagulum, and avulsed tissue.6 Because this procedure does not involve catheter manipulation in the aortic root or aortic valve, dislodged calcium and cholesterol plaque probably do not have a role in ACE lesion production as …

Comparison of effects on coagulation and inflammatory markers using a duty-cycled bipolar and unipolar radiofrequency pulmonary vein ablation catheter vs. a cryoballoon catheter for pulmonary vein isolation

Thrombo-embolic events are one of the most feared complications related to atrial fibrillation (AF) ablation. Since radiofrequency (RF) energy is thought to be associated with a higher risk of thrombus formation than cryoenergy, the purpose of this study was to assess if the degree of activation of coagulation and inflammatory markers differed between ablation procedures performed with a cryoballoon catheter vs. a RF energy-based pulmonary vein ablation catheter (PVAC), respectively. Thirty patients referred for AF ablation were randomized to pulmonary vein isolation with either the cryoballoon or the PVAC. Biomarkers were studied for endothelial damage (von Willebrand factor antigen), platelet activation (soluble P-selectin), and coagulation activity [prothrombin fragment 1 + 2 (F1 + 2) and D-dimer] at five different time points during the procedure. Troponin I (Trop I) and C-reactive protein were analysed to reflect myocardial destruction and inflammatory activity. Markers of endothelial damage and platelet activation increased after ablation in both the cryo and the RF group. Similarly, the D-dimer levels increased significantly (P = 0.001) in both groups, whereas the F1 + 2 levels increased after the transseptal puncture only (P = 0.001). The overall activation of the coagulation system was, however, comparable between the groups. The cryoballoon was associated with higher Trop I compared with the PVAC (P < 0.001), but the ratios between biomarkers and Trop I were higher with the PVAC than with the cryoballoon. Even though the cryoballoon causes a higher degree of myocardial destruction than the PVAC, markers of coagulation, endothelial damage, and inflammation were comparable between the two techniques.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Culture-negative bivalvular endocarditis with myocardial destruction in a patient with systemic lupus erythematosus: a case report

Culture-negative endocarditis has long been associated with systemic lupus erythematosus, but is usually asymptomatic or involves a single valve. We present a patient with destructive culture-negative endocarditis that remains without a microbial etiology despite an exhaustive workup using advanced diagnostic techniques in a patient with systemic lupus erythematosus.

Relation of cardiac troponin I and microvascular obstruction following ST-elevation myocardial infarction

Presence of microvascular obstruction (MVO) following primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) confers higher risk of left-ventricular remodelling and dysfunction. Measurement of cardiac troponin I (cTnI) after STEMI reflects the extent of myocardial destruction. We aimed to explore whether cTnI values were associated with presence of MVO independently of infarct size in STEMI patients receiving pPCI. 175 patients with STEMI were included. cTnI was sampled at 24 and 48 h. MVO and infarct size was determined by delayed enhancement with cardiac magnetic resonance at five to seven days post index event. The presence of MVO following STEMI was associated with larger infarct size and higher values of cTnI at 24 and 48 h. For any given infarct size or cTnI value, there was a greater risk of MVO development in non-anterior infarctions. cTnI was strongly associated with MVO in both anterior and non-anterior infarctions (P < 0.01) after adjustment for covariates (including infarct size); and was reasonably effective in predicting MVO in individual patients (area-under-the-curve ≥0.81). Presence of MVO is reflected in levels of cTnI sampled at an early time-point following STEMI and this association persists after adjustment for infarct size.

Evaluation of the Efficacy of Granulocytic Colony-Stimulating Factor for the Treatment of Experimental Myocardial Destruction in Mice

We studied the effects of recombinant granulocytic CSF on heart remodeling in BALB/c mice after cryodestruction. Administration of granulocytic CSF was started 1 day after cryodestruction (subcutaneously, 10 μg/kg/day, for 4 days). As early as after the first injection, leukocytosis in the peripheral blood started to develop, leukocyte count peaked on days 4-6 and returned to normal on day 14. Treatment with granulocytic CSF significantly increased the content of progenitor cells in the bone marrow and led to rapid development of the inflammatory reaction and myocardium infiltration with mononuclear cells. Injections of granulocytic CSF did not reduce scar area, but provided significantly less pronounced heart hypertrophy, which attests to its better functional properties. By day 30 after cryodestruction, control animals and animals receiving granulocytic CSF exhibited similar morphological picture at the site of damage. Thus, our regimen of granulocytic CSF administration produced a mobilizing effect on bone marrow progenitor cells and postinfarction heart remodeling. Direct effects of granulocytic CSF on the heart have to be established for its use in the treatment of myocardial infarction.

IL-17 Produced during Trypanosoma cruzi Infection Plays a Central Role in Regulating Parasite-Induced Myocarditis

BackgroundChagas disease is a neglected disease caused by the intracellular parasite Trypanosoma cruzi. Around 30% of the infected patients develop chronic cardiomyopathy or megasyndromes, which are high-cost morbid conditions. Immune response against myocardial self-antigens and exacerbated Th1 cytokine production has been associated with the pathogenesis of the disease. As IL-17 is involved in the pathogenesis of several autoimmune, inflammatory and infectious diseases, we investigated its role during the infection with T. cruzi.Methodology/Principal FindingsFirst, we detected significant amounts of CD4, CD8 and NK cells producing IL-17 after incubating live parasites with spleen cells from normal BALB/c mice. IL-17 is also produced in vivo by CD4+, CD8+ and NK cells from BALB/c mice on the early acute phase of infection. Treatment of infected mice with anti-mouse IL-17 mAb resulted in increased myocarditis, premature mortality, and decreased parasite load in the heart. IL-17 neutralization resulted in increased production of IL-12, IFN-γ and TNF-α and enhanced specific type 1 chemokine and chemokine receptors expression. Moreover, the results showed that IL-17 regulates T-bet, RORγt and STAT-3 expression in the heart, showing that IL-17 controls the differentiation of Th1 cells in infected mice.Conclusion/SignificanceThese results show that IL-17 controls the resistance to T. cruzi infection in mice regulating the Th1 cells differentiation, cytokine and chemokine production and control parasite-induced myocarditis, regulating the influx of inflammatory cells to the heart tissue. Correlations between the levels of IL-17, the extent of myocardial destruction, and the evolution of cardiac disease could identify a clinical marker of disease progression and may help in the design of alternative therapies for the control of chronic morbidity of chagasic patients.

Relation of Cardiac Troponin I Measurements at 24 and 48 Hours to Magnetic Resonance–Determined Infarct Size in Patients With ST-Elevation Myocardial Infarction

Levels of circulating cardiac troponin I (cTnI) or T are correlated to extent of myocardial destruction after an acute myocardial infarction. Few studies analyzing this relation have employed a second-generation cTnI assay or cardiac magnetic resonance (CMR) as the imaging end point. In this post hoc study of the Efficacy of FX06 in the Prevention of Mycoardial Reperfusion Injury (F.I.R.E.) trial, we aimed at determining the correlation between single-point cTnI measurements and CMR-estimated infarct size at 5 to 7 days and 4 months after a first-time ST-elevation myocardial infarction (STEMI) and investigating whether cTnI might provide independent prognostic information regarding infarct size at 4 months even taking into account early infarct size. Two hundred twenty-seven patients with a first-time STEMI were included in F.I.R.E. All patients received primary percutaneous coronary intervention within 6 hours from onset of symptoms. cTnI was measured at 24 and 48 hours after admission. CMR was conducted within 1 week of the index event (5 to 7 days) and at 4 months. Pearson correlations (r) for infarct size and cTnI at 24 hours were r = 0.66 (5 days) and r = 0.63 (4 months) and those for cTnI at 48 hours were r = 0.67 (5 days) and r = 0.65 (4 months). In a multiple regression analysis for predicting infarct size at 4 months (n = 141), cTnI and infarct location retained an independent prognostic role even taking into account early infarct size. In conclusion, a single-point cTnI measurement taken early after a first-time STEMI is a useful marker for infarct size and might also supplement early CMR evaluation in prediction of infarct size at 4 months.