ABSTRACT
Background Coronary risk stratification is recommended for emergency department patients with chest pain. Many protocols are designed as "rule-out" binary classification strategies, while others use graded-risk stratification. The comparative performance of competing approaches at varying levels of risk tolerance has not been widely reported. Methods and Results This is a prospective cohort study of adult patients with chest pain presenting between January 2018 and December 2019 to 13 medical center emergency departments within an integrated healthcare delivery system. Using an electronic clinical decision support interface, we externally validated and assessed the net benefit (at varying risk thresholds) of several coronary risk scores (History, ECG, Age, Risk Factors, and Troponin [HEART] score, HEART pathway, Emergency Department Assessment of Chest Pain Score Accelerated Diagnostic Protocol), troponin-only strategies (fourth-generation assay), unstructured physician gestalt, and a novel risk algorithm (RISTRA-ACS). The primary outcome was 60-day major adverse cardiac event defined as myocardial infarction, cardiac arrest, cardiogenic shock, coronary revascularization, or all-cause mortality. There were 13 192 patient encounters included with a 60-day major adverse cardiac event incidence of 3.7%. RISTRA-ACS and HEART pathway had the lowest negative likelihood ratios (0.06, 95% CI, 0.03-0.10 and 0.07, 95% CI, 0.04-0.11, respectively) and the greatest net benefit across a range of low-risk thresholds. RISTRA-ACS demonstrated the highest discrimination for 60-day major adverse cardiac event (area under the receiver operating characteristic curve 0.92, 95% CI, 0.91-0.94, P<0.0001). Conclusions RISTRA-ACS and HEART pathway were the optimal rule-out approaches, while RISTRA-ACS was the best-performing graded-risk approach. RISTRA-ACS offers promise as a versatile single approach to emergency department coronary risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03286179.
Subject(s)
Chest Pain/diagnosis , Decision Support Systems, Clinical , Electrocardiography/methods , Emergency Service, Hospital/statistics & numerical data , Risk Assessment/methods , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Chest Pain/blood , Chest Pain/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Prospective Studies , ROC Curve , Risk Factors , Survival Rate/trends , Time Factors , Troponin/blood , United States/epidemiology , Young AdultABSTRACT
Mitochondrial diseases are rare, often go undiagnosed and can lead to devastating cascades of multisystem organ dysfunction. This report of a young woman with hearing loss and gestational diabetes illustrates a novel presentation of a cardiomyopathy caused by a previously described mutation in a mitochondrial gene, MT-TL1. She initially had biventricular heart dysfunction and ventricular arrhythmia that ultimately recovered with beta blockade and time. She continues to participate in sport without decline. It is important to keep mitochondrial diseases in the differential diagnosis and understand the testing and management strategies in order to provide the best patient care.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Cardiomyopathies/diagnosis , Mitochondrial Myopathies/diagnosis , RNA, Transfer, Leu/genetics , Tachycardia, Ventricular/genetics , Adult , Cardiomyopathies/complications , Cardiomyopathies/drug therapy , Cardiomyopathies/genetics , Coronary Angiography , DNA Mutational Analysis , Diagnosis, Differential , Echocardiography , Female , Genetic Testing , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Magnetic Resonance Imaging , Martial Arts/physiology , Mitochondrial Myopathies/complications , Mitochondrial Myopathies/drug therapy , Mitochondrial Myopathies/genetics , Mutation , Tachycardia, Ventricular/diagnosis , Treatment Outcome , Troponin/bloodABSTRACT
OBJECTIVES: Coronary risk scores are commonly applied to emergency department patients with undifferentiated chest pain. Two prominent risk score-based protocols are the Emergency Department Assessment of Chest pain Score Accelerated Diagnostic Protocol (EDACS-ADP) and the History, ECG, Age, Risk factors, and Troponin (HEART) pathway. Since prospective documentation of these risk determinations can be challenging to obtain, quality improvement projects could benefit from automated retrospective risk score classification methodologies. METHODS: EDACS-ADP and HEART pathway data elements were prospectively collected using a Web-based electronic clinical decision support (eCDS) tool over a 24-month period (2018-2019) among patients presenting with chest pain to 13 EDs within an integrated health system. Data elements were also extracted and processed electronically (retrospectively) from the electronic health record (EHR) for the same patients. The primary outcome was agreement between the prospective/eCDS and retrospective/EHR data sets on dichotomous risk protocol classification, as assessed by kappa statistics (ĸ). RESULTS: There were 12,110 eligible eCDS uses during the study period, of which 66 and 47% were low-risk encounters by EDACS-ADP and HEART pathway, respectively. Agreement on low-risk status was acceptable for EDACS-ADP (ĸ = 0.73, 95% confidence interval [CI] = 0.72 to 0.75) and HEART pathway (ĸ = 0.69, 95% CI = 0.68 to 0.70) and for the continuous scores (interclass correlation coefficients = 0.87 and 0.84 for EDACS and HEART, respectively). CONCLUSIONS: Automated retrospective determination of low risk status by either the EDACS-ADP or the HEART pathway provides acceptable agreement compared to prospective score calculations, providing a feasible risk adjustment option for use in large data set analyses.
Subject(s)
Chest Pain/diagnosis , Decision Support Systems, Clinical/standards , Emergency Service, Hospital/organization & administration , Aged , Electrocardiography , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Assessment/methods , Troponin/bloodABSTRACT
BACKGROUND: Although patients with coronary artery disease (CAD) rely increasingly upon percutaneous coronary intervention (PCI), this therapy causes subsequent the complications of myocardial injury. Acupuncture safely protects the heart from ischemic injury; however, the efficacy of acupuncture for periprocedural myocardial injury after PCI remains unclear. METHODS: Seven databases in English and Chinese including PubMed, Web of Science, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database will be searched. Randomized controlled trials (RCTs) that use acupuncture to treat PCI-related myocardial injury in patients with CAD, regardless of blinding. The crossover randomized trials will be included, but only the pre-crossover data will be analyzed to avoid carryover effects. We will exclude non-RCTs, qualitative studies, uncontrolled clinical trials, and laboratory studies. The measurement of concentration of cardiac troponin (T or I) and MB isoenzyme of creatine kinase will be used as primary outcome. Postprocedural cardiac function and the major adverse cardiac/cerebrovascular event rate will be assessed as secondary outcome. Relevant data were collected independently by 2 reviewers and the third reviewer was responsible for resolving discrepancies through discussion. The Review Manager V.5.3.3 s will be used to perform the data synthesis and subgroup analysis. DISCUSSION: This systematic review and meta-analysis would provide convincing evidence of various types of acupuncture that specifically focuses on cardioprotective effect of acupuncture on PCI-related myocardial injury. REGISTRATION: Open Science Framework (OSF) registries (osf.io/n2e6t) with the registration DOI: 10.17605/OSF.IO/79H2E.
Subject(s)
Acupuncture Therapy/methods , Coronary Artery Disease/therapy , Myocardial Ischemia/therapy , Percutaneous Coronary Intervention/adverse effects , Acupuncture Therapy/statistics & numerical data , Cardiotonic Agents/pharmacology , Coronary Artery Disease/complications , Coronary Artery Disease/pathology , Creatine Kinase, MB Form/blood , Humans , Myocardial Ischemia/blood , Myocardial Ischemia/etiology , Myocardial Ischemia/prevention & control , Percutaneous Coronary Intervention/methods , Perioperative Period , Randomized Controlled Trials as Topic , Sensitivity and Specificity , Troponin/blood , Meta-Analysis as TopicABSTRACT
Carbon monoxide (CO) poisoning presents with many different cardiac effects, but one important presentation is its effect as a CO stress test to reveal underlying coronary artery disease (CAD). There are a limited number of publications detailing this phenomenon, but after CO intoxication it is important to suspect CAD in association with mild troponin leak or non-ST segment elevation myocardial infarction (NSTEMI) shown on electrocardiogram (EKG). We recently treated three patients with CO poisoning who had underlying CAD. In the first case a man presented to the emergency department with CO toxicity and an ST segment elevation myocardial infarction (STEMI), resulting in emergent angioplasty and the discovery of severe CAD. The second case involved an individual who presented with CO poisoning with rising troponin levels. An angioplasty discovered a stable 90% occlusion. The third case was a patient with CO poisoning and transient inferior T wave inversion EKG with borderline troponin elevation. Angioplasty showed only 30% occlusion, so the patient's presentation was likely due to direct CO cardiac toxicity. These cases demonstrate the varied presentations that CO poisoning can have on patients with underlying heart disease.
Subject(s)
Carbon Monoxide Poisoning , Coronary Artery Disease/diagnosis , Exercise Test , Troponin/blood , Aged , Angioplasty, Balloon, Coronary , Carbon Monoxide Poisoning/blood , Carbon Monoxide Poisoning/therapy , Coronary Artery Disease/blood , Electrocardiography , Humans , Hyperbaric Oxygenation , Male , Middle Aged , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/therapy , Stents , Thrombosis/diagnosis , Thrombosis/therapyABSTRACT
The popularity of pre-workout supplements is rising amongst professional athletes and fitness enthusiasts. Despite increased usage, the safety profile of pre-workout supplements is likely to be not well understood. Additionally, many different brands use various undisclosed proprietary blends of active ingredients creating safety regulation difficulties. This lack of oversight could prove unsafe for certain patients. This patient MK is a 33-year-old healthy housewife who presented with central chest tightness, pre-syncope and mild dyspnoea to the emergency department via ambulance. The presentation was in the context of recent strenuous exercise and ingestion of a pre-workout supplement (Alpha Lean-7). Most striking in her presentation was a troponin rise of 50 ng/L, while not very high it is unusual given her lack of cardiac risk factors. She had a 3-day uneventful admission with a downtrending troponin prior to discharge. This case highlights the possible dangers of pharmacologically active ingredients in pre-workout supplements.
Subject(s)
Dietary Supplements/adverse effects , Myocardial Ischemia/etiology , Running/physiology , Adult , Caffeine/adverse effects , Central Nervous System Stimulants/adverse effects , Dyspnea/etiology , Emergency Service, Hospital , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Myocardial Ischemia/blood , Syncope/etiology , Troponin/bloodABSTRACT
STUDY OBJECTIVE: Professional guidelines recommend 72-hour cardiac stress testing after an emergency department (ED) evaluation for possible acute coronary syndrome. There are limited data on actual compliance rates and effect on patient outcomes. Our aim is to describe rates of completion of noninvasive cardiac stress testing and associated 30-day major adverse cardiac events. METHODS: We conducted a retrospective analysis of ED encounters from June 2015 to June 2017 across 13 community EDs within an integrated health system in Southern California. The study population included all adults with a chest pain diagnosis, troponin value, and discharge with an order for an outpatient cardiac stress test. The primary outcome was the proportion of patients who completed an outpatient stress test within the recommended 3 days, 4 to 30 days, or not at all. Secondary analysis described the 30-day incidence of major adverse cardiac events. RESULTS: During the study period, 24,459 patients presented with a chest pain evaluation requiring troponin analysis and stress test ordering from the ED. Of these, we studied the 7,988 patients who were discharged home to complete diagnostic testing, having been deemed appropriate by the treating clinicians for an outpatient stress test. The stress test completion rate was 31.3% within 3 days and 58.7% between 4 and 30 days, and 10.0% of patients did not complete the ordered test. The 30-day rates of major adverse cardiac events were low (death 0.0%, acute myocardial infarction 0.7%, and revascularization 0.3%). Rapid receipt of stress testing was not associated with improved 30-day major adverse cardiac events (odds ratio 0.92; 95% confidence interval 0.55 to 1.54). CONCLUSION: Less than one third of patients completed outpatient stress testing within the guideline-recommended 3 days after initial evaluation. More important, the low adverse event rates suggest that selective outpatient stress testing is safe. In this cohort of patients selected for outpatient cardiac stress testing in a well-integrated health system, there does not appear to be any associated benefit of stress testing within 3 days, nor within 30 days, compared with those who never received testing at all. The lack of benefit of obtaining timely testing, in combination with low rates of objective adverse events, may warrant reassessment of the current guidelines.
Subject(s)
Acute Coronary Syndrome/diagnosis , Chest Pain/diagnosis , Exercise Test/standards , Myocardial Infarction/diagnosis , Acute Coronary Syndrome/mortality , Acute Disease , Aged , Chest Pain/etiology , Clinical Decision-Making , Emergency Service, Hospital , Exercise Test/methods , Exercise Test/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Male , Mortality/trends , Myocardial Infarction/epidemiology , Myocardial Revascularization/statistics & numerical data , Observational Studies as Topic , Outcome Assessment, Health Care , Patient Discharge/trends , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Spain/epidemiology , Troponin/bloodABSTRACT
BACKGROUND: Doxorubicin is a well-established chemotherapeutic agent for the treatment of childhood acute lymphoblastic leukemia (ALL), but its efficacy is often limited by its related cardiotoxicity. Protection against doxorubicin-induced cardiotoxicity can be of great value, especially for children. Silymarin has a potent antioxidant property that can be helpful in preventing cardio-toxicity. OBJECTIVE: 'To assess the possible protective role of silymarin against early doxorubicin-induced cardiotoxicity in children with ALL'. SUBJECTS AND METHODS: This study was conducted on 80 children with ALL, including 40 patients under doxorubicin therapy and silymarin 420 mg/day for one week after each doxorubicin dose starting from the day of doxorubicin infusion (Group I) and 40 patients under doxorubicin therapy and placebo (Group II). 'Conventional echo-Doppler measures of left ventricular systolic and diastolic functions and pulsed wave tissue Doppler of lateral mitral annulus were done for all patients'. RESULTS: After doxorubicin therapy, there was a significant higher reduction of systolic function [ejection fraction (EF), fraction shortening (FS) and s wave] in Group II compared with Group I and non-significant reduction of diastolic function [E/A ratio or e/a ratio] in both Groups. Although serum troponin increases in both groups after doxorubicin therapy, the increase of troponin is significantly lower in group I compared with group II. CONCLUSION: Silymarin decreased early Doxorubicin-induced left ventricular systolic function disturbances and can be recommended as an adjuvant drug in patients with ALL under doxorubicin therapy. RECOMMENDATION: 'Multicenter studies on a large number of patients with longer follow up' periods to prove the protective role of silymarin in early and late Doxorubicin-induced cardiotoxicity.
Subject(s)
Cardiotonic Agents/therapeutic use , Cardiotoxicity/prevention & control , Doxorubicin/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Silymarin/therapeutic use , Adolescent , Cardiotoxicity/etiology , Child , Child, Preschool , Echocardiography, Doppler , Female , Heart Diseases/chemically induced , Heart Diseases/diagnostic imaging , Heart Diseases/prevention & control , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Troponin/blood , Ventricular Function, Left/drug effectsABSTRACT
BACKGROUND: Heart failure (HF) is the end stage of many heart diseases, and ischemic heart disease (IHD) is the primary cause. Yiqi Fumai lyophilized injection, a contemporary Chinese medicine preparation, widely used in the treatment of IHF patients, shows clinical efficacy on improving symptoms and cardiac function, but the quality of the current literature does not address multiple important issues. This article describes a protocol for assessment of complementary treatment with Yiqi Fumai lyophilized injection in acute decompensated IHD. METHODS: The protocol is designed as a multicenter randomized controlled trial to assess the efficacy and safety of complementary treatment with Yiqi Fumai lyophilized injection on acute decompensated IHD. This trial will be carried out in 37 hospitals in China and expected to enroll 666 inpatients with acute decompensated IHF due to coronary heart disease. On the basis of standardized western medications, patients are randomized to either the treatment group (250 ml 5% glucose / sodium injection + 5.2 g Yiqi Fumai lyophilized injection) or the control group for 7 days and follow-up for 30 ± 3 and 60 ± 3 days. The primary outcome is change in brain natriuretic peptide (BNP) concentrations. The secondary outcomes are composite endpoint, left ventricular ejection fraction, blood troponin T/I, cardiothoracic ratio, life quality scale, scores of the four traditional Chinese medicine (TCM) diagnostic methods. DISCUSSION: Standardized western medications together with TCM have been extensively used in China and have developed into a comprehensive treatment model. The trial will provide clinical research evidence for application of complementary treatment with intravenous Yiqi Fumai lyophilized injection on decompensated IHF. TRIAL REGISTRATION: This study protocol has been listed in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-15007396, http://www.chictr.org.cn/showproj.aspx?proj=12370 ) on November 6, 2015.
Subject(s)
Cardiovascular Agents/administration & dosage , Drugs, Chinese Herbal/administration & dosage , Heart Failure/drug therapy , Myocardial Ischemia/complications , Adult , Aged , Biomarkers/blood , Cardiovascular Agents/adverse effects , China , Drug Compounding , Drugs, Chinese Herbal/adverse effects , Female , Freeze Drying , Heart Failure/blood , Heart Failure/etiology , Heart Failure/physiopathology , Humans , Injections, Intravenous , Male , Middle Aged , Multicenter Studies as Topic , Myocardial Ischemia/physiopathology , Natriuretic Peptide, Brain/blood , Randomized Controlled Trials as Topic , Stroke Volume/drug effects , Treatment Outcome , Troponin/blood , Ventricular Function, Left/drug effectsABSTRACT
Myocardial injury is a frequent consequence of moderate to severe CO (carbon monoxide) poisoning and a significant predictor of mortality in CO injury. Electrocardiography (ECG) is an easily accessible diagnostic tool for evaluating myocardial damage. Increased QT interval and QT dispersion are related to heterogeneity of regional ventricular repolarization and can develop into arrhythmias. It has been reported that QT interval and QT dispersion increase in patients with CO poisoning. Hyperbaric oxygen (HBO2) therapy has been used successfully in treating patients with CO poisoning. The aim of this study was to investigate change of corrected QT (QTc) interval and QTc dispersion after HBO2 therapy. This study included 31 patients with CO poisoning. QTc dispersion increased in patients with CO poisoning. The mean QTc dispersion was 54.94 milliseconds (ms) on admission. The mean QTc dispersion decreased to 35.74 ms after HBO2 therapy (P=0.003). There was also a correlation between carboxyhemoglobin level and QTc dispersion (P=0.029). HBO2 therapy, which decreases QTc dispersion, may improve the myocardial electrical homogeneity and reduce the risk of ventricular arrhythmia and cardiac death. Physicians should be aware of the effect of HBO2 therapy on myocardial damage when treating patients with CO poisoning. The ECGs should be examined carefully before referring or excluding HBO2 therapy.
Subject(s)
Arrhythmias, Cardiac/therapy , Carbon Monoxide Poisoning/therapy , Hyperbaric Oxygenation/methods , Adult , Aged , Aged, 80 and over , Arrhythmias, Cardiac/blood , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Carbon Monoxide Poisoning/blood , Carbon Monoxide Poisoning/complications , Carbon Monoxide Poisoning/physiopathology , Electrocardiography , Female , Humans , Male , Middle Aged , Troponin/blood , Young AdultABSTRACT
Ischemic heart disease is the leading cause of mortality worldwide. The purpose of this study was to evaluate the cardioprotective effects of pomegranate juice in patients with ischemic heart disease. One hundred patients, diagnosed with unstable angina or myocardial infarction, were randomly assigned to the test and the control groups (n = 50, each). During 5 days of hospitalization, in addition to the conventional medical therapies, the test groups received 220 mL pomegranate juice, daily. During the hospitalization period, the blood pressure, heart rate, as well as the intensity, occurrence, and duration of the angina were evaluated on a regular basis. At the end of the hospitalization period, the serum levels of malondialdehyde, interleukin-6, and tumor necrosis factor alpha were measured in all patients. The levels of serum troponin and high-sensitive C-reactive protein levels were also assayed in patients diagnosed with myocardial infarction. Pomegranate juice caused significant reductions in the intensity, occurrence, and duration of angina pectoris in patients with unstable angina. Consistently, the test patients had significantly lower levels of serum troponin and malondialdehyde. Other studied parameters did not change significantly. The results of this study suggest protective effects of pomegranate juice against myocardial ischemia and reperfusion injury. Copyright © 2017 John Wiley & Sons, Ltd.
Subject(s)
Cardiotonic Agents/pharmacology , Coronary Artery Disease/drug therapy , Fruit and Vegetable Juices , Lythraceae/chemistry , Myocardial Ischemia/drug therapy , Aged , Angina, Unstable/drug therapy , C-Reactive Protein/analysis , Female , Humans , Interleukin-6/blood , Male , Malondialdehyde/blood , Middle Aged , Myocardial Infarction/drug therapy , Polyphenols/pharmacology , Reperfusion Injury/drug therapy , Troponin/blood , Tumor Necrosis Factor-alpha/bloodABSTRACT
Troponin assays are integral to the diagnosis of acute myocardial infarction (AMI), but there is concern that testing is over utilized and may not conform to published guidelines. We reviewed all testing performed at 14 hospitals over 12 months and associated troponin values with the primary and secondary diagnoses for each visit. Troponin was determined to be negative, indeterminate or elevated based on reference ranges. The majority of troponin measurements were single, not serial (64%). The rate of AMI was low, with only 3.5% of tested patients having a primary or secondary diagnosis of AMI. Sensitivity, specificity and negative predictive value were excellent, exceeding 90%. However, positive predictive value was low, suggesting testing of populations with diseases known to be associated with elevated troponin levels in the absence of AMI. The majority (79%) of elevated troponin values were associated with primary diagnoses other than AMI. Only 28% of elevated troponins were associated with a primary or secondary diagnosis of AMI. These data suggest possible overuse of troponin testing in our healthcare system. Journal of Hospital Medicine 2017;12:329-331.
Subject(s)
Delivery of Health Care, Integrated/standards , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Troponin/blood , Biomarkers/blood , Humans , Retrospective StudiesABSTRACT
OBJECTIVE: Although ED patients presenting with supraventricular tachycardia (SVT) are commonly investigated, the value of these investigations has been questioned. We aimed to determine the frequency and utility of investigations in patients with SVT. METHODS: We undertook an explicit retrospective medical record audit of patients with SVT who presented to a single ED (January 2004 to June 2014). Data on demographics, presenting complaints, investigations and outcomes were extracted. The outcomes were nature and utility of investigations. RESULTS: A total of 633 patients were enrolled (mean [SD] age 55.4 [17.7] years, 62% female). Laboratory investigations were common: electrolytes (83.7% of patients), full blood count (81.2%), magnesium (57.5%), calcium (39.3%) and thyroid function (30.3%). These investigations revealed many mildly abnormal results but resulted in electrolyte supplementation in only 19 patients: eight with mild hypokalaemia (potassium 3.0-3.5 mmol/L) and 11 with mild hypomagnesia (magnesium 0.49-1.1 mmol/L). Troponin was ordered for 302 (47.7%) patients, many of whom had no history or risk factors for cardiac disease, or ischaemic symptoms associated with their SVT. The troponin was normal, mildly and moderately elevated in 65.2, 24.5 and 10.2% of cases, respectively. Only seven (1.1%) patients were diagnosed with acute myocardial ischemia. Although 190 (30.0%) patients had a chest X-ray (CXR), it was normal in 78.4% of cases. All CXR abnormalities were incidental and not relevant to the immediate ED management. CONCLUSION: Patients with uncomplicated SVT are over-investigated. Guidelines for ED SVT investigation are recommended. Further research is recommended to determine the indications for each investigation in the setting of SVT.
Subject(s)
Tachycardia, Supraventricular/chemically induced , Tachycardia, Supraventricular/physiopathology , Adult , Aged , Female , Humans , Hypercalciuria/complications , Hypercalciuria/etiology , Hypokalemia/complications , Hypokalemia/etiology , Male , Middle Aged , Nephrocalcinosis/complications , Nephrocalcinosis/etiology , Radiography/methods , Renal Tubular Transport, Inborn Errors/complications , Renal Tubular Transport, Inborn Errors/etiology , Retrospective Studies , Troponin/analysis , Troponin/bloodABSTRACT
Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.
Subject(s)
CREB-Binding Protein/metabolism , Fruit/chemistry , Iridoid Glycosides/pharmacology , Myocardial Ischemia/drug therapy , Phytotherapy , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Verbena/chemistry , Animals , Blotting, Western , CREB-Binding Protein/drug effects , Cell Line/drug effects , Cell Survival/drug effects , Creatine Kinase/blood , Disease Models, Animal , Hypoxia/drug therapy , Iridoid Glycosides/isolation & purification , Male , Plant Extracts/chemistry , Proto-Oncogene Proteins c-akt/drug effects , Rats, Sprague-Dawley , Troponin/bloodABSTRACT
BACKGROUND: Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX-induced cardiotoxicity forms the major cumulative dose-limiting factor. Glutamine and ω-3 polyunsaturated fatty acids (PUFAs) are putatively cardioprotective during various stresses and/or have potential chemosensitizing effects during cancer chemotherapy. METHODS: Antitumor activity and cardiotoxicity of DOX treatment were evaluated simultaneously in a MatBIII mammary adenocarcinoma tumor-bearing rat model treated with DOX (cumulative dose 12 mg/kg). Single or combined treatment of parenteral glutamine (0.35 g/kg) and ω-3 PUFAs (0.19 g/kg eicosapentaenoic acid and 0.18 g/kg docosahexaenoic acid) was administered every other day, starting 6 days before chemotherapy initiation until the end of study (day 50). RESULTS: Glutamine alone significantly prevented DOX-related deterioration of cardiac function, reduced serum cardiac troponin I levels, and diminished cardiac lipid peroxidation while not affecting tumor inhibition kinetics. Single ω-3 PUFA treatment significantly enhanced antitumor activity of DOX associated with intensified tumoral oxidative stress and enhanced tumoral DOX concentration while not potentiating cardiac dysfunction or increasing cardiac oxidative stress. Intriguingly, providing glutamine and ω-3 PUFAs together did not consistently confer a greater benefit; conversely, individual benefits on cardiotoxicity and chemosensitization were mostly attenuated or completely lost when combined. CONCLUSIONS: Our data demonstrate an interesting differentiality or even dichotomy in the response of tumor and host to single parenteral glutamine and ω-3 PUFA treatments. The intriguing glutamine × ω-3 PUFA interaction observed draws into question the common assumption that there are additive benefits of combinations of nutrients that are beneficial on an individual basis.
Subject(s)
Antineoplastic Agents/adverse effects , Cardiotoxicity/drug therapy , Doxorubicin/adverse effects , Fatty Acids, Omega-3/pharmacology , Glutamine/pharmacology , Heart/drug effects , Animals , Apoptosis/drug effects , Arginase/metabolism , Caspase 3/genetics , Caspase 3/metabolism , Female , HSP70 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/metabolism , Homeostasis , Lipid Peroxidation/drug effects , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Nutritional Status , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Rats , Rats, Inbred F344 , Treatment Outcome , Troponin/bloodABSTRACT
Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.
Subject(s)
Animals , Male , Myocardial Ischemia/drug therapy , Verbena/chemistry , CREB-Binding Protein/metabolism , Iridoid Glycosides/pharmacology , Fruit/chemistry , Phytotherapy , Troponin/blood , Cell Line/drug effects , Cell Survival/drug effects , Blotting, Western , Rats, Sprague-Dawley , Creatine Kinase/blood , Disease Models, Animal , CREB-Binding Protein/drug effects , Iridoid Glycosides/isolation & purification , Hypoxia/drug therapyABSTRACT
Black widow spider envenomation generally results in self-limiting pain that can be treated in the emergency department (ED) with analgesics and benzodiazepines, usually with no further intervention. Occasionally, a patient has to be admitted or treated with antivenom for refractory pain or a venom-induced complication. We present the case of an 84-year-old man who presented to our ED with chest pain and dyspnea after being bitten on the foot by a western black widow spider (Lactrodectus hesperus). His initial cardiac troponin I (cTnI) was elevated at 0.07 ng/ml and continued to rise to a peak of 0.17 ng/ml. He also had rhabdomyolysis, another uncommon complication of black widow envenomation. An elevated cTnI generally signifies myocardial injury and is rarely seen after black widow envenomation. We discuss the possible etiologies for an elevated cardiac biomarker, in this context, and review potentially serious complications of widow spider envenomation presenting with chest symptoms and an elevated cardiac biomarker.
Subject(s)
Black Widow Spider , Chest Pain/etiology , Spider Bites/blood , Troponin/blood , Aged, 80 and over , Animals , Chest Pain/blood , Chest Pain/diagnosis , Electrocardiography , Emergency Service, Hospital , Humans , Male , Spider Bites/complicationsABSTRACT
To investigate the effects of different doses of abnormal Savda Munziq on myocardial ischemia-reperfusion injury (MI/RI) in rats with the abnormal Savda syndrome, 50 abnormal Savda animal models were randomly divided into a control group, a model group, a high-dose group, a middle-dose group, and a low-dose group, with each group containing 10 rats. The enzyme-linked immunosorbent assay was used to detect the serum myocardial enzyme and troponin levels, and hematoxylin and eosin (HE) staining was used to observe changes of the myocardial tissues in the different groups. Results showed that in the Munziq intervention groups, the serum creatine kinase and troponin levels were significantly lower than those in the model group, and the middle-dose group showed the lowest levels. The HE staining of myocardial tissue showed that the myocardial edema and muscle fiber proliferation levels were significantly higher in the Munziq intervention groups than in the model group, and the middle-dose group showed the least cardiac tissue damage. Therefore, intervention with an intermediate Munziq dose could significantly reduce MI/RI in rats with abnormal Savda syndrome.
Subject(s)
Cardiotonic Agents/pharmacology , Creatine Kinase/blood , Medicine, East Asian Traditional , Myocardial Reperfusion Injury/drug therapy , Troponin/blood , Animals , China , Dose-Response Relationship, Drug , Female , Male , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/pathology , Myocardium/metabolism , Myocardium/pathology , RatsABSTRACT
Myocardial ischemia/reperfusion (MIR) injury easily occurrs during cardiopulmonary bypass surgery in elderly patients. In an attempt to develop an effective strategy, we employed a pig model of MIR injury to investigate the maximum rate of change of left ventricular pressure, left ventricular enddiastolic pressure, and left intraventricular pressure. Coronary sinus cardiac troponin T (TnT) and adenosine-triphosphate (ATP) content in myocardium were measured. The ultrastructures for MIR injury were visualized by transmission electron microscopy (TEM). The role of δ-opioid receptor activation using D-Ala2, D-Leu5-enkephalin (DADLE) in both early (D1) and late (D2) phases of cardioprotection was identified. Also, the merit of cardioprotection by DADLE in combination with anisodamine, the muscarinic receptor antagonist (D+M), was evaluated. Glibenclamide was employed at the dose sufficient to block ATP-sensitive potassium channels. Significant higher cardiac indicators, reduced TnT and increased ATP contents, were observed in D1, D2, and D+M groups compared with the control group. DADLE induced protection was better in later phase of ischemia that was attenuated by glibenclamide. DADLE after the ischemia showed no benefit, but combined treatment with anisodamine showed a marked postischemic cardioprotection. Thus, anisodamine is helpful in combination with DADLE for postischemic cardioprotection.
Subject(s)
Cardiopulmonary Bypass/adverse effects , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/etiology , Myocardial Reperfusion Injury/prevention & control , Receptors, Opioid, delta/metabolism , Solanaceous Alkaloids/therapeutic use , Adenosine Triphosphate/metabolism , Animals , Cell Shape/drug effects , Coronary Sinus/drug effects , Coronary Sinus/metabolism , Coronary Sinus/pathology , Coronary Sinus/physiopathology , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Heart Function Tests , Myocardial Reperfusion Injury/blood , Myocardium/enzymology , Myocardium/pathology , Myocardium/ultrastructure , Protein Kinase C/metabolism , Solanaceous Alkaloids/pharmacology , Sus scrofa , Troponin/bloodABSTRACT
AIMS: Prophylactic corticosteroids have been reported to attenuate the increase in C-reactive protein (CRP) and the incidence of atrial fibrillation (AF) both after heart surgery and AF ablation. We tested the impact of a single prophylactic corticosteroid dose on ultrasensitive CRP 24 h and 14 days after extensive linear atrial ablation (8 mm or 3.5 irrigated tip) guided by electroanatomical mapping (NavX) in pigs with normal hearts. METHODS AND RESULTS: Pigs (n = 19; 35 kg) were divided into three groups: corticoid (n = 7), atrial ablation with administration of 500 mg methylprednisolone intravenous at anaesthetic induction; control (n = 7), atrial ablation only; and sham (n = 5), surgical procedure without ablation. Troponin and CRP were measured before, 24 h and 14 days after the procedure. After sacrifice, lesions were analysed macroscopically and histologically. Linear lesions were created in the right (n = 23) and left (n = 21) atrium of 14 animals, with no difference between groups. In all groups there was elevation of troponin and CRP 24 h after ablation, with a return to baseline values after 14 days. However, CRP levels of the control, corticoid, and sham groups were similar at all three time points analysed (baseline P = 0.52, 24 h P = 0.21, 14 days P = 0.66). Histological analysis did not show any difference between corticoid and control groups. CONCLUSION: In this model, extensive biatrial RF ablation, per se, does not promote systemic inflammation. The use of a prophylactic single corticoid dose before ablation did not prevent systemic inflammation or alter the healing of the lesions.