Increase In Cardiac Enzymes Research Articles

Impact of Cerium Oxide Nanoparticles on Metabolic, Apoptotic, Autophagic and Antioxidant Changes in Doxorubicin-Induced Cardiomyopathy: Possible Underlying Mechanisms.

In the current study, the effects of cerium oxide nanoparticles (nanocerium; NC) on doxorubicin (DOX)-induced cardiomyopathy and its possible underlying mechanisms were addressed. 32 adult male rats were allocated into 4 groups; i) control group, ii) NC group; rats received NC (0.2 mg/kg, i.p., daily), iii) DOX group; rats received DOX 4 mg/kg (2 injections with a 14-day interval), and iv) DOX+NC group as DOX but rats received NC. At the end of the experiment, ECG and ECHO recordings and assessments of the levels of cardiac enzymes (CK-MB, LDH), and myocardial oxidative stress (MDA, catalase, and GSH), the expression of LC3 and beclin1 (markers of autophagy), caspase3 (marker of apoptosis) by immunohistochemistry, the expression of acetyl-CoA carboxylase alpha (ACCA) by PCR, and 5'adenosine monophosphate-activated protein kinase (AMPK) levels in the heart tissues were performed. The DOX group displayed a prolonged corrected QT interval, an increase in cardiac enzymes (CK-MB and LDH), myocardial oxidative stress (high MDA with low catalase and GSH), expression of ACCA, caspase-3, beclin1, and LC3 in myocardial tissues, with reduction in myocardial AMPK levels, and myocardial contractility (low ejection fraction, and fractional shortening). On the other hand, administration of NC with DOX resulted in significant improvement of all studied parameters. NC offers a cardioprotective effect against DOX-induced cardiomyopathy. This effect might be due to its antioxidant and antiapoptotic effects as well as to the modulation of autophagy and metabolic dysfunctions induced by DOX in the heart tissues.

Clozapine-induced myocarditis: a case report and literature review

IntroductionWe present the case of a male patient, 47 years old, diagnosed with schizophrenia, that was admitted at our hospital presenting a confusional state, with agitation, motor discoordination and difficulty breathing. At the blood analyses there was evidence of an increase in cardiac enzymes. The clinical manifestations had begun 5 days before, with slight leucocytosis showing in a routine blood test made after initiating clozapine, followed by fever, vomiting and progressive impairment of general clinical state.ObjectivesTo describe a case of clozapine-induced myocarditis, which is a known, but rare, side effect of clozapine and to do a brief review of the existing knowledge on this matter.MethodsThe authors undertook an article review using PubMed database and a thorough analysis of the clinical case.ResultsThe hypothesis of clozapine-induced myocarditis was the main diagnosis considered since the beginning, nevertheless, a thorough clinical examination and complementary tests were made and all the previous psychopharmacological treatment was suspended. The final diagnosis was based on the clinical presentation (fever, vomiting, shortness of breath, confusion and impairment of general state), the elevation of CRP, PCT and TnI and findings on echocardiogram that suggested myocarditis (moderate systolic dysfunction of the left ventricle due to global hypokinesia and a non dilated left ventricle).ConclusionsThe clinical manifestations observed, the results of the complementary diagnostic tests and the review of the existing literature, allowed to make the diagnosis of clozapine-induced myocarditis. We find of considerable importance to continue to publish and study this matter as it is still insufficiently known.DisclosureNo significant relationships.

Protective Effect of Kaempferol and Its Nanoparticles on 5-Fluorouracil-Induced Cardiotoxicity in Rats.

Background Fluorouracil (5-FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5-FU-associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti-inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5-FU-induced cardiotoxicity in rats. Methods Thirty Male Wistar rats were divided into five groups as follows: control, 5-FU, 5-FU+10 mg/kg vitamin C, 5-FU+ 1 mg/kg KPF, and 5-FU+ 1 mg/kg KPF-NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF-NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. Results 5-FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX-2 (cyclooxygenase-2) expression, and histopathological degenerations. 5-FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF-NPs reduced oxidative stress, cardiac enzymes, COX-2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF-NPs. Conclusion Our results demonstrated that treatment with KPF and KPF-NPs significantly improved cardiotoxicity induced by 5-FU in rats.

Colchicine Ameliorates 5-Fluorouracil-Induced Cardiotoxicity in Rats.

Background and Objective. 5-Fluorouracil is one of the most common chemotherapeutic agents used in the treatment of solid tumors. 5-Fluorouracil-associated cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Colchicine is a strong anti-inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. And also, its protective effects on cardiovascular disease have been reported in various studies. The current study is aimed at appraising the effect of colchicine on 5-fluorouracil-induced cardiotoxicity in rats. Methods. Twenty male Wistar rats were divided into four groups as follows: control, 5-fluorouracil, colchicine (5 mg/kg), and 5-fluorouracil+5 mg/kg colchicine. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-fluorouracil (100 mg/kg). The control group received normal saline, and the treatment groups received colchicine with an intraperitoneal injection for 14 days. Findings. 5-Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase-2 and tumor necrosis factor-alpha expression, cardiac enzymes, and histopathological degenerations. 5-Fluorouracil treatment also decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. In addition, 5-fluorouracil disrupted electrocardiographic parameters, including increased elevation in the ST segment and increased QRS duration. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase-2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Moreover, body weight loss was hampered after treatment with colchicine. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5-fluorouracil in rats.

Cardioprotective effect of allyl isothiocyanate in a rat model of doxorubicin acute toxicity

Doxorubicin (DOX) is an effective anthracycline chemotherapeutic drug. Nevertheless, the cardiotoxicity adverse effect restricts its clinical benefit. Allyl isothiocyanate (AITC) is a natural antioxidant and anti-inflammatory agent. In the present study, we investigated the effect of AITC on cardiotoxicity of DOX. Thirty-two adult male albino rats were divided into four groups; control, AITC, DOX, and AITC + DOX. AITC was administrated orally (25 mg/kg/day) for 7 days, and DOX was given as a single i.p. injection (15 mg/kg) on the third day. Mortality rate was observed during the experiment. Cardiac toxicity markers (lactate dehydrogenase (LDH), creatine kinase (CK-MB), and cardiac Troponin I (cTn-I)) were evaluated in serum samples obtained from all groups after 48 hours of DOX injection. DOX-treated group showed 40% mortality and a significant increase in cardiac enzymes. This increase was accompanied by degenerated cardiomyocytes, and inflammatory cells infiltrates. Interestingly, AITC administration alleviated myocardial oxidative stress induced by DOX as attenuated the increase in malondialdehyde (MDA), and nitric oxide (NO) while resulted in elevations of the antioxidant reduced glutathione (GSH) level as well as superoxide dismutase (SOD) activity. Furthermore, the inflammatory cytokine, TNF-α, was reduced upon administration of AITC with DOX. The cardio-protection of AITC is attributed to increase the expression of cytoprotective nuclear factor erythroid 2-related factor 2 (Nrf2). Subsequently, heme oxygenase 1 (HO-1) level was elevated by AITC to correct the oxidative stress induced by DOX in the heart. Accordingly, AITC ameliorated acute cardiotoxicity associated with DOX treatment via attenuation of oxidative stress and the induced-tissue inflammatory injury. Abbreviations: DOX: doxrubicin; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase 1; AITC: ally isothiocyanate; MDA: malondialdehyde; SOD: superoxide dismutase; GSH: reduced glutathione; TNF-α: tumor necrosis factor alpha.

Dose-Dependent Cardioprotective Effect of Hemin in Doxorubicin-Induced Cardiotoxicity Via Nrf-2/HO-1 and TLR-5/NF-κB/TNF-α Signaling Pathways.

Doxorubicin (DOX) is one of the most widely used chemotherapeutic drugs, but its cardiotoxicity has been shown to be a dose-restricting factor during therapy. Finding new agents for reducing these complications is still in critical need. The current study aimed to evaluate the possible cardioprotective effect of hemin (HEM) in DOX-induced cardiotoxicity and exploring the role of toll like receptor-5/nuclear factor kappa-B/tumor necrosis factor-alpha (TLR-5/NF-κB/TNF-α) and nuclear factor erythroid 2-related factor-2/hemeoxygenase-1 (Nrf-2/HO-1) signaling pathways in mediating such effect. Wistar albino rats were randomly divided into five groups. They were administered DOX by interaperitoneal (i.p.) injection (15mg/kg) on the 5th day of the experiment with or without HEM in different doses (2.5, 5, 10mg/kg/day) i.p. for 7days. Results showed that the DOX group had cardiotoxicity as manifested by a significant increase in cardiac enzymes, malondialdehyde (MDA), TLR-5, NF-κB, TNF-α, and cleaved caspase-3 levels with toxic histopathological changes. Based on these findings, HEM succeeded in reducing DOX-induced cardiotoxicity in a dose-dependent effect by stimulation of Nrf-2/HO-1 and inhibition of TLR-5/NF-κB/TNF-α pathways with subsequent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Malignant Arrhythmia in Acute Conus Artery Occlusion

We present the case of a 74 y.o. woman with multiple cardiovascular risk factors, admitted for worsening angina over the past three weeks. On admission she had no significant electrocardiographic and echocardiographic changes and a negative Troponin test. Coronary angiography revealed single vessel disease: severe stenosis of the right coronary artery (RCA) ostium (difficult to assess visually), 50% mid-vessel and 60% distal segment. The left anterior descending artery and circumflex artery had non-significant stenoses. Fractional flow reserve technique (FFR) was used to evaluate the RCA ostial lesion which proved to be significant, therefore angioplasty with three drug-eluting stents was performed for all three lesions of the right coronary artery, starting from the ostium. Due to its location, minimal aortic protrusion of the first stent occluded a small ostial branch which proved to be the conus artery and the patient developed mild transient angina during the procedure, but with good outcome regarding the intracoronary flow. After the angioplasty the patient presented anterior leads ST-elevation and developed mild chest pain with an increase in cardiac enzymes (CK-MB peak 39 U/L). Later on, she had two episodes of ventricular fibrillation with rapid defibrillation to sinus rhythm, with no further events or echocardiographic changes and no recurrent angina. The patient was started on amiodarone to prevent ventricular arrhythmias and continued double antiplatelet therapy with aspirin and clopidogrel. She was discharged six days later. In conclusion, although the conus branch is a small artery, its acute occlusion can have significant life-threatening complications.

Malignant Arrhythmia in Acute Conus Artery Occlusion

We present the case of a 74 y.o. woman with multiple cardiovascular risk factors, admitted for worsening angina over the past three weeks. On admission she had no significant electrocardiographic and echocardiographic changes and a negative Troponin test. Coronary angiography revealed single vessel disease: severe stenosis of the right coronary artery (RCA) ostium (difficult to assess visually), 50% mid-vessel and 60% distal segment. The left anterior descending artery and circumflex artery had non-significant stenoses. Fractional flow reserve technique (FFR) was used to evaluate the RCA ostial lesion which proved to be significant, therefore angioplasty with three drug-eluting stents was performed for all three lesions of the right coronary artery, starting from the ostium. Due to its location, minimal aortic protrusion of the first stent occluded a small ostial branch which proved to be the conus artery and the patient developed mild transient angina during the procedure, but with good outcome regarding the intracoronary flow. After the angioplasty the patient presented anterior leads ST-elevation and developed mild chest pain with an increase in cardiac enzymes (CK-MB peak 39 U/L). Later on, she had two episodes of ventricular fibrillation with rapid defibrillation to sinus rhythm, with no further events or echocardiographic changes and no recurrent angina. The patient was started on amiodarone to prevent ventricular arrhythmias and continued double antiplatelet therapy with aspirin and clopidogrel. She was discharged six days later. In conclusion, although the conus branch is a small artery, its acute occlusion can have significant life-threatening complications.

Evaluation of Cardiology consultations during the COVID-19 Pandemic Period

In this study, we scientifically examined the consultations of the patients being hospitalized from the other departments to the cardiology department during Coronavirus Disease 2019 (COVID-19) pandemia. Consultations to the cardiology department between 01 April-31 May 2020 and 01 April-31 May 2019 were discussed. Demographic characteristics and reasons of consultations were compared. A different approach was f ollowed in COVID-19 patients diagnosed with compared to patients in other clinics. The rate of consulted patients in 2019 year was 14.4% (866/5989). Its rate in 2020 year was found as 18.5% (462/2486) (p: <0.001). A statistically significant difference was obtained in both groups. The use of drugs prolonging the Qt, preoperative and increase in cardiac enzymes were found statistically significant in terms of the consultations (p: <0.001-<0.001-0.003-0.016, respectively). Face to face interviews were made in 29% (33/114) of the patients who were consulted from COVID-19 clinics. In 71% (81/114) patients, electrocardiography (ECG) s were evaluated digitally. In this study, although there was a decrease in the number of hospitalized patients during the COVID-19 pandemia, we observed an increase in the number of patients being consulted to cardiology clinic. The relationship between COVID-19 disease and cardiovascular diseases and drugs being used in the treatment increased the workload of the cardiology clinic during the pandemic period.

Safety and efficacy of early discharge and outpatient rehabilitation after myocardial infarction for low-risk patients

Guidelines recommend early discharge and rehabilitation after ST-elevation myocardial infarction (STEMI) in low-risk patients. However, low risk is not established according to well-defined criteria and often it depends on subjective judgment. The aim of this real-life study is to confirm that early discharge is safe in patients at low risk according to selected criteria and subsequent outpatient rehabilitation is associated with clinical benefits. Patients with STEMI treated with primary percutaneous coronary intervention from October 2010 to October 2017, identified as being at low risk (according to predefined criteria), discharged by day 5, were studied retrospectively. Basal characteristics and 30-day outcome were evaluated and a comparison was made between patients who completed or did not complete outpatient rehabilitation. We enrolled 193 STEMI patients treated with percutaneous coronary intervention for STEMI, early discharged and at low risk: 132 completed outpatient rehabilitation and 61 did not. The increase in cardiac enzymes and the occurrence of arrhythmias were the only independent predictors of completion of outpatient rehabilitation. After 30 days from discharge, adverse events were rare and not significantly different between groups. Optimal pharmacological therapy was achieved more often in the rehabilitation group (58.3% vs 44.3%; p<0.05). Early discharge within 5 days of STEMI has been proved feasible and safe in our population of well-defined low-risk patients. Early participation in a rehabilitation program was associated with a more adequate titration of therapy.

Clinical Characteristics and Long-Term Mortality Rate in Female Patients with Takotsubo Syndrome Compared with Female Patients with ST-Elevation Acute Myocardial Infarction: A Retrospective Study from a Single Center

Background Takotsubo syndrome (TTS) is characterized by acute transient, stress-induced, left ventricular systolic dysfunction, generally presenting with apical ballooning. It can mimic an acute coronary syndrome, but with a milder increase in cardiac enzymes and without culprit coronary artery disease on angiography. Data on long-term follow-up and survival in patients with TTS, compared with patients with ST-elevation myocardial infarction (STEMI), are scarce. Purpose To assess all-cause mortality rate and survival in a consecutive series of female patients with TTS compared with age- and sex-matched STEMI patients on long-term follow-up. Methods and Results We collected data of 65 TTS female patients (TTS group) with a mean age of 73.42 ± 11.35 years from 2001 to 2013. Collection of follow-up information was concluded for all patients in 2016. To compare the mortality and survival of TTS patients with those of the STEMI population, we used data from our STEMI Registry, a prospective registry of 7446 STEMI patients admitted from 2001 to 2013 to our cath-lab for primary percutaneous coronary intervention (p-PCI). From the registry, we selected 104 STEMI patients (STEMI group) comparable to our TTS group in terms of age (mean age of 72.33 ± 11.92 years) and sex. On follow-up examination after a median of 1000 days, the TTS group had a lower all-cause mortality rate than the STEMI group (7.69% versus 23.08%). This difference was statistically different between the two groups (log-rank test, p value = 0.03). Conclusions In our study, TTS and STEMI patients displayed a statistically significant difference in long-term survival. Specifically, the TTS group had a lower mortality rate than the STEMI group. This seems to suggest that TTS and STEMI are two different clinical entities with two different clinical outcomes.

Effects of low dose of aliskiren on isoproterenol-induced acute myocardial infarction in rats.

This study examined the effects of aliskiren (Ali) (direct renin inhibitor) on serum cardiac enzymes (LDH and CK-MB), electrocardiography (ECG) changes, myocardial oxidative stress markers (MDA, CAT, and GSH) and the expression of Bcl2, HO-1, and Nrf2 genes in isoproterenol (ISO)-induced myocardial infarction (MI). A total of 40 male albino rats were allocated into four groups, (1) normal control (NC) group, (2) Ali group (rats received Ali at 10mg/kg/day p.o. for 5days), (3) ISO group (rats received ISO 150mg/kg i.p. for two consecutive days at 24h intervals), and (4) Ali + ISO group (rats received ISO + Ali at 10mg/kg/day p.o. for 5 days from the 2nd dose of ISO). ISO group showed significant rise in serum cardiac enzymes (CK-MB and LDH), myocardial damage scores, myocardial MDA, HO-1, myocardial Nrf2 expression with significant reduction in myocardial antioxidants (CAT and GSH), and Bcl2 expression compared to the normal group (p < 0.05). ECG showed ST segment elevation, prolonged QT interval and QRS complex, and increased heart rate in ISO group. Co-administration of Ali and ISO caused significant increase in cardiac enzymes and morphology with increase in MDA, serum K, and creatinine with significant decrease in Bcl2, HO-1, and Nrf2 without significant changes in ECG parameters compared to ISO group. We concluded that low dose of Ali seems to exacerbate the myocardial injury in ISO-MI, which might be due to the enhanced oxidative stress and apoptosis.

Kounis Syndrome (Type I) Following Bee Sting

Bee stings are commonly encountered worldwide. Various manifestations after bee sting have been described 1 . Local reactions are common. Unusually, manifestations like vomiting, diarrhoea, dyspnoea, generalised oedema, acute renal failure, hypotension and collapse may occur. Rarely vasculitis, serum sickness, neuritis and encephalitis have been described which generally develop days to weeks after a sting. Acute coronary syndromes after hymenoptera stings and other environmental exposures are referred to as the Kounis syndrome or allergic myocardial ischaemia and infarction. The three variants of Kounis syndrome are Type I variant: includes patients with normal coronary arteries without predisposing factors for coronary artery disease in whom the acute release of inflammatory mediators can induce either coronary artery spasm without increase of cardiac enzymes and troponins or coronary artery spasm progressing to acute myocardial infarction with raised cardiac enzymes and troponins. Type II variant: includes patients with culprit but quiescent pre-existing atheromatous disease in whom the acute release of inflammatory mediators can induce either coronary artery spasm with normal cardiac enzymes and troponins or plaque erosion or rupture manifesting as acute myocardial infarction. Type III variant: includes patients with coronary thrombosis (including stent thrombosis) in whom aspirated thrombus specimens stained with hematoxylin-eosin and Giemsa demonstrate the presence of eosinophils and mast cells respectively. We report a 23 year old male who developed myocardial infarction after multiple bee stings over his body.

Long-Term Outcomes for Different Forms of Stress Cardiomyopathy After Surgical Treatment for Subarachnoid Hemorrhage.

Stress-induced cardiomyopathy (SCM) after subarachnoid hemorrhage (SAH) includes predominant apical or basal regional left ventricular dysfunction (RLVD) with concomitant changes in electrocardiogram or increase in cardiac enzymes. We hypothesized that difference in outcome is associated with the type of RLVD after SAH. We studied a single-center retrospective cohort of SAH patients hospitalized between 2000 and 2010 with follow-up until 2013. We classified patients who had an echocardiogram for clinically indicated reasons according to the predominate location of RLVD as classic SCM-apical form and variant SCM-basal form. A Cox proportional hazard model and logistic regression were used to estimate the risk for death and hospital complications associated with different RLVD after adjustment for propensity to undergo echocardiography given clinical characteristics on admission. Among 715 SAH patients, 28% (200/715) had an echocardiogram for clinical evidence of cardiac dysfunction during hospitalization, the most common being acute left ventricular dysfunction, suspected acute ischemic event, changes in electrocardiogram and cardiac enzymes, and arrhythmia. SCM was present in 59 patients (8% of all cohort and 30% of patients with echocardiogram, respectively) with similar distribution of SCM-basal (25/59) and SCM-apical forms (34/59). SAH patients who had an echocardiogram for clinically indicated reasons had a significantly decreased risk-adjusted long-term survival compared with those without an echocardiogram, regardless of the presence of RLVD. SCM-basal form was associated with cardiac complications (odds ratio, 6.1; 99% confidence interval, 1.8-20.2) and severe sepsis (odds ratio, 5.3; 99% confidence interval, 1.6-17.2). SAH patients with echocardiogram for a clinically indicated reason have a decreased long-term survival, regardless of the presence of RLVD. The association between severe sepsis and SCM-basal warrants future studies to determine their potential synergistic effect on left ventricular systolic dysfunction among SAH patients.

Aborted myocardial infarction in patients undergoing primary percutaneous coronary intervention

Introduction. The outcome of patients with ST-elevation myocardial infarction (STEMI) strongly depends on a successful reperfusion. In some patients receiving an effective treatment myocardial infarction can be aborted.Aim. The aim of the study was to estimate the incidence, clinical outcome, prognosis and inflammatory response in patients with aborted MI.Material and methods. 119 consecutive patients with STEMI treated with a primary percutaneous coronary intervention (pPCI) were enrolled in the study. Aborted MI was diagnosed when the maximal increase in cardiac enzymes (CK-MB) was up to twice the upper limit of normal (CK-MB ? 50 U/I) and at least 50% reduction of ST-segment deviation was observed within 90 min of pPCI.Results. Aborted MI was diagnosed in 16 subjects (13.4%). Patients with the aborted MI had lower serum troponin I levels (p &lt; 0.0001). The time to treatment was significantly shorter in the aborted MI group (101 min vs. 220 min, p &lt; 0.00001). Patients with aborted MI had a lower corrected TIMI frame count (p &lt; 0.05) and a lower wall motion score index (p &lt; 0.005), less pronounced inflammatory response (lower serum levels of IL-6, p &lt; 0.01, and MCP-1, p &lt; 0.05), higher ejection fraction six months after MI (72% vs. 64%, p &lt; 0.05). None of the aborted MI patients died during the 3-year follow-up, while there were 13 deaths among patients with non-aborted MI.Conclusions. The abortion of myocardial infarction results in a better outcome and more favorable prognosis. An inflammatory response is less pronounced in the aborted MI.

Successful anesthesia in a patient with a history of cardiac arrest following rocuronium injection.

Successful anesthesia in a patient with a history of cardiac arrest following rocuronium injection.

Intraoperative interfascicular ventricular tachycardia: A rare occurrence

Intraoperative interfascicular ventricular tachycardia: A rare occurrence

Development of cardiac hypertrophy by sunitinib in vivo and in vitro rat cardiomyocytes is influenced by the aryl hydrocarbon receptor signaling pathway

Sunitinib (SUN) is a new tyrosine kinase inhibitor that possesses both anti-angiogenic and anti-tumor activities. Although SUN has improved survival rate in cancer patients, cardiotoxicity has been reported as a significant side effect. Several studies suggested a role for the aryl hydrocarbon receptor (AhR) and its regulated genes such as cytochrome P4501A1 (CYP1A1) in the pathogenesis of heart failure and cardiac hypertrophy. To test the hypothesis that SUN induces cardiac hypertrophy through the modulation of AhR, Wistar albino rats were treated for 15 and 30 days with increasing doses of SUN (25, 50, and 100 mg/kg), whereas at the in vitro level, rat cardiomyocyte H9c2 cells were incubated with SUN (1, 2.5, and 5 μM). Thereafter, cardiac hypertrophy parameters were determined at the biochemical, histopathology, and gene expression levels. SUN treatment causes increase in cardiac enzymes, changes in histopathology, and induction in several hypertrophic markers. This was associated with proportional increase in the CYP1A1 gene in a concentration- and time-dependent manner. The direct involvement of AhR in the SUN-induced cardiac hypertrophy in H9c2 cells was supported by the ability of resveratrol, an AhR antagonist, to block the SUN-induced hypertrophy and the ability of SB203580, a novel AhR agonist, to potentiate SUN-induced hypertrophic genes. This is the first demonstration that SUN induces hypertrophic genes in vivo and in vitro rat cardiomyocyte through AhR/CYP1A1-mediated mechanism.

Recognizing and treating myocarditis in recent-onset systemic sclerosis heart disease: Potential utility of immunosuppressive therapy in cardiac damage progression

ObjectivesScleroderma heart disease is a major risk of death in systemic sclerosis (SSc). Mechanisms underlying myocardial damage are still unclear. We performed an extensive study of SSc patients with recent-onset symptoms for heart disease and examined the efficacy of immunosuppressive therapy. MethodsA cohort of 181 SSc patients was enrolled. Of these, 7 patients newly developed clinical symptoms of heart disease (heart failure, chest pain, and palpitation); all of them showed mild but persistent increase in cardiac enzymes. These patients underwent Holter ECG, 2D-echocardiography, perfusional scintigraphy, delayed-enhancement-cardiac magnetic resonance (DE-CMR), coronary angiography, and endomyocardial biopsy. Patients were treated for at least 12 months and followed-up for 5 years. ResultsVentricular ectopic beats (VEBs) were found in 4 patients, wall motion abnormalities in 3, pericardial effusion in 6, and DE in CMR in 6 with T2-hyperintensity in 2. In all patients, histology showed upregulation of endothelium adhesion molecules and infiltration of activated T lymphocytes, with (acute/active myocarditis in 6) or without (chronic/borderline myocarditis in 1) myocyte necrosis. Parvovirus B19 genome was detected in 3. None showed occlusion of coronary arteries or microvessels. Compared with SSc controls, these patients more often had early disease, skeletal myositis, c-ANCA/anti-PR3 positivity, VEBs, pericardial effusion, and systolic and/or diastolic dysfunction. Immunosuppressive therapy improved symptoms and led to cardiac enzyme negativization; however, 2 patients died of sudden death during follow-up. ConclusionsMyocarditis is a common finding in SSc patients with recent-onset cardiac involvement. Its early detection allowed to timely start an immunosuppressive treatment, preventing cardiac damage progression in most cases.

Akut koroner sendromlu hastalarda endotelyal progenitör hücre sayımı

Aim. Endothelial progenitor cells repair related region by removal of damaged endothelial cells mechanically or replacing endothelial cells via migration from bone marrow to peripheric blood pool with stimulus of cytokines. Previously, it has been shown that number of these cells decrease in chronic stage of stable coronary heart disease, whereas they increase in number in acute coronary syndromes. The aim of this study is to investigate the difference in the number of endothelial progenitor cells among subgroups of acute coronary syndrome (ST elevation myocardial infarction, non-ST elevation myocardial infarction and unstable angina pectoris ) in patients hospitalized in coronary intensive care unit. Method. The study data were analysed in two steps. In the first step, it has been investigated whether there were any differences regarding endothelial progenitor cell count among three subgroups of acute coronary syndrome (n=112). In the second step, a further 13 patients who were hospitalized with a prediagnosis of unstabil angina pectoris and subsequently reported to have normal echocardiography and coronary angiography were also enrolled. The patients were divided into two groups; the patients with unstabil angina pectoris of whom no increase in cardiac enzymes detected indicating the absence of any cardiac damage and patients with normal coronary angiography findings constituted the first group (Grup A, n=41) and the patients with ST elevation myocardial infarction and non-ST elevation myocardial infarction of whom an increase in cardiac enzymes detected indicating a documented cardiac damage constituted the second group (Grup B, n=84). We investigated whether there were any differences regarding endothelial progenitor cell count between these two groups. Results. Our results indicate that the number of endothelial progenitor cells did not differ significantly among these three groups in the first step (3.87 ± 2.74, 5.46 ± 6.38 and 3.95 ± 2.94, respectively; p=0.232). The results of the statistical analysis also revealed no differences between Grup A and Grup B regarding EPC counts (3.89 ± 2.81 vs 4.80 ± 5.22; p=0.302). Conclusion. In the light of these data, in coronary heart disease in which resistance to treatment is a topical problem despite improvements in therapeutic modalities, further clinical studies are needed about the number and the functions of these cells in the bone marrow and peripheric blood, their effects on target tissues and the factors regulating them, for theurapeutic use of these cells.