Serum free L-carnitine in association with myoglobin as a diagnostic marker of acute myocardial infarction

BackgroundEarly diagnosis of acute myocardial infarction (AMI) in patients with chest pain is necessary to initiate appropriate treatment. Elevation of ST-segment in ECG is the only marker that cardiologists depend on in diagnosis. The aim of this study was to monitor the level of serum free L-carnitine in combination with myoglobin (Myo) and creatine kinase (total activity and CK-MB level) for usefulness as a predictor of AMI in ICU patients.Design and methodsIn the present study serum total CK activity and CK-MB, Myo, and free L-carnitine levels were determined in 90 patients admitted to the ICU at Ain Shams University Hospital and correlated the sensitivity and specificity of each parameter.ResultsObtained data revealed that, 47/90 who were diagnosed as AMI showed a highly significant reduction in serum free L-carnitine level in all cases as compared to normal control (P < 0.001), 24/90 diagnosed as unstable angina showed a non significant reduction of serum carnitine and 19/90 who were diagnosed as noncardiac showed non significant changes in the level of serum free carnitine as compared to normal control. In addition, serum free L-carnitine level was negatively correlated to CK-MB and Myo (r = ? 0.61 and ? 0.52) respectively. The sensitivity of carnitine assay was considerably higher (95.5%) compared to CK-MB (87%) and Myo (89.5%) even considering patients with a short delay until admission.ConclusionComparing the changes in serum total CK, levels of CK-MB, Myo and carnitine, the sensitivity and specificity were significantly higher for serum free L-carnitine. For this reason, serum free L-carnitine can be used as a good predictor for AMI diagnosis from other diseases.     

LCx: a diagnostic alternative for the early detection of Mycobacterium tuberculosis complex

This study aims to evaluate the performance of a new diagnostic method (LCx Tuberculosis Assay, Abbott Laboratories) based on Ligase Chain Reaction (LCR) technology, for the detection of Mycobacterium tuberculosis in respiratory and non-respiratory specimens and compare it with standard microbiological data and the clinical diagnosis of tuberculosis. Nine hundred specimens were collected from patients with a high suspicion of tuberculosis (740 respiratory samples and 160 non-respiratory specimens). The study was divided into two separate groups: samples washed and distilled water (207 samples) and unwashed samples that were directly resuspended in phosphate buffer (693 samples). The overall sensitivity, specificity, positive and negative predictive values of samples washed with distilled water after decontamination with SDS-NaOH were: 54%, 100%, 100%, and 94%, respectively. If these results were divided according to origin of specimens, the sensitivity, specificity, positive and negative predictive values in respiratory and non-respiratory samples were 54.5%, 100%, 100%, 94% and 50 100%, 100%, 93%, respectively. In contrast, for the non-washed samples, values were 85%, 95%, 80% and 98%, respectively. Respiratory and non-respiratory samples gave values of 84%, 96%, 77%, and 97.5% versus 89%, 99%, 94%, and 98%. The LCx M. tuberculosis assay is a novel, semi-automated assay and a rapid and highly specific technique for screening all forms of tuberculosis, including non-respiratory forms.     

Annexin V detection of lipopolysaccharide-induced cardiac apoptosis

Acute inflammatory response to lipopolysaccharide (LPS) exposure is typically associated with cardiac myocyte apoptosis, which is difficult to quantify because of heart tissue specificity. We report here that radioiodinated Annexin V (I-AnxV), a specific ligand of phosphatidylserine exposed by apoptotic cells, allows tissue detection of apoptosis in LPS-treated rat hearts. Heart I-AnxV uptake was significantly increased in all cardiac territories of LPS-treated rats. In contrast, I-human serum albumin myocardial uptake was only slightly increased in LPS-treated rat hearts, suggesting limited changes in vascular protein permeability. Autoradiography of endotoxin-treated rat heart sections with I-AnxV in association with deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling and caspase 3 staining allows identification of double positive cardiac myocytes. Inhibition of apoptosis by caspase inhibitors (i.e., ZVAD.fmk and DEVD.cmk) reduced I-AnxV myocardial uptake in LPS-treated rats. Eventually, endotoxin-treated rats displayed pathological uptake of Tc-annexin in the cardiac mediastinal region whereas zVAD.fmk reduced Tc-annexin mediastinal uptake. Our results show that radioactive I-AnxV signal emerging from LPS-treated rat hearts could be related to the activation of caspase-dependent apoptotic pathway in cardiac myocytes.     

Study of a myoglobin test in patients hospitalized for suspected myocardial infarction

An immunoagglutination latex test was studied in comparison with a plasma myoglobin radioimmunoassay in 103 subjects with suspected myocardial infarction. The test provided an early and reliable indication of raised plasma myoglobin (greater than 85 micrograms/l), a biochemical marker for the early phase (12 h) of myocardial infarction. The diagnostic values (sensitivity and specificity) studied over a 36 h period were the same as those for the plasma myoglobin assay. The sensitivity was similar to that of creatine kinase activity and better than that of the creatine kinase MB/creatine kinase ratio; the lower specificity was due to false-positive results in some subjects with angina. The myoglobin test, which provides rapid results, may be substituted in early diagnosis of myocardial infarction for the plasma myoglobin assay which is unsuitable for emergency analysis.     

Evaluation of urinary myoglobin assay test for myocardial infarction.

Serial determinations of urinary myoglobulin, beta2-microglobulin and albumin, and of serum myoglobin, were performed in twenty-eight consecutive patients admitted to a coronary care unit. Patients with myocardial infarction (MI patients) all had higher serum levels of myoglobin then those with other diagnoses (OBS patients). Myoglobinuria occurred in 80% of MI patients and in half of the OBS patients. The appearance of myoglobin in urine was mainly accounted for by an impaired renal reabsorption of low molecular weight proteins. Measurement of urinary myoglobulin, in contrast to serum myoglobulin, is of little value for the diagnosis of myocardial infarction.     

Genetic blockade of lymphangiogenesis does not impair cardiac function after myocardial infarction

In recent decades, treatments for myocardial infarction (MI), such as stem and progenitor cell therapy, have attracted considerable scientific and clinical attention but failed to improve patient outcomes. These efforts indicate that more rigorous mechanistic and functional testing of potential MI therapies is required. Recent studies have suggested that augmenting post-MI lymphatic growth via VEGF-C administration improves cardiac function. However, the mechanisms underlying this proposed therapeutic approach remain vague and untested. To more rigorously test the role of lymphatic vessel growth after MI, we examined the post-MI cardiac function of mice in which lymphangiogenesis had been blocked genetically by pan-endothelial or lymphatic endothelial loss of the lymphangiogenic receptor VEGFR3 or global loss of the VEGF-C and VEGF-D ligands. The results obtained using all 3 genetic approaches were highly concordant and demonstrated that loss of lymphatic vessel growth did not impair left ventricular ejection fraction 2 weeks after MI in mice. We observed a trend toward excess fluid in the infarcted region of the left ventricle, but immune cell infiltration and clearance were unchanged with loss of expanded lymphatics. These studies refute the hypothesis that lymphangiogenesis contributes significantly to cardiac function after MI, and suggest that any effect of exogenous VEGF-C is likely to be mediated by nonlymphangiogenic mechanisms.     

Ability of myoglobin to predict mortality in patients admitted for exclusion of myocardial infarction

Background

Myoglobin can be used as an early marker to diagnose myocardial infarction (MI); and although nonspecific for myocardial necrosis, it seems to be a strong mortality predictor. Because myoglobin elevations are often present in patients with renal insufficiency, it is possible that the predictive value of myoglobin is secondary to identifying patients with renal insufficiency.

Methods

Consecutive patients admitted for MI exclusion without ST elevation on the initial electrocardiogram underwent serial assessment of cardiac markers (creatine kinase [CK], CK–myocardial band [MB], and troponin I [TnI]). Myoglobin was assessed at the time of admission and/or 3 hours later. Renal insufficiency was defined as a creatinine clearance <60 mL/min. Multivariate analysis was performed to identify predictors of 30-day and 1-year all-cause mortality.

Results

A total of 3461 patients were included in the analysis. Overall 30-day and 1-year mortality was 2.4% and 9.7%. Myoglobin was elevated in 675 (20%), CK-MB in 421 (12%), and TnI in 517 (15%). Among the 993 patients with renal insufficiency, myoglobin was elevated in 43%, CK-MB in 17%, and TnI in 21%. Independent predictors of 30-day and 1-year mortality were similar and included age ≥65 years, prior MI, and an ischemic electrocardiogram, whereas myoglobin was the strongest multivariate predictor (odds ratio [OR] 2.8, 95% confidence interval [CI] 2.1-3.7), including those with renal insufficiency (OR 2.3, 95% CI 1.6-3.4). Troponin I had borderline predictive value (P = .08, OR 1.4, 95% CI 0.96-2.0), whereas CK-MB was not predictive in either group.

Conclusions

Despite the absence of cardiac specificity, an elevated myoglobin strongly predicts mortality, even in patients with renal insufficiency.     

The diagnostic value of troponin T and myoglobin levels in acute myocardial infarction: a study in Turkish patients

This study compares the diagnostic value of troponin T (TnT) and myoglobin with creatinine kinase (CK) for myocardial infarction (MI) in a tertiary care centre in a developing nation. The study group comprised 33 acute myocardial infarction patients and 27 healthy controls. Receiver operating characteristic curves for TnT, myoglobin and CK were drawn and areas under the curve calculated. At admission, myoglobin levels had greater diagnostic sensitivity than TnT or CK levels. After 2 h, myoglobin and TnT had equal sensitivity and specificity, whereas CK still had lower sensitivity than myoglobin and TnT. After 4 h there was no difference between the tests. It was concluded that myoglobin levels on admission and TnT at 2 h had the greatest diagnostic rate, whereas all the tests were similar after 4 h for MI.     

肌钙蛋白Ⅰ在急性心肌梗死早期诊断和心肌再梗死中的价值

目的探讨心肌肌钙蛋白I(cTnI)在急性心肌梗死(AMI)早期诊断和心肌再梗死中的价值。方法测定131例AMI发作2～10 h患者的血清cTnI和肌酸激酶同工酶(CK-MB)的浓度,并以122名健康体检者作对照,绘制并分析受试者工作特征(ROC)曲线。结果AMI组发病早期血清cTnI和CK-MB水平与对照组相比差异有统计学意义(P<0.01);AMI后2～10 h cTnI和CK-MB的ROC曲线下面积(AUC)分别为:0.925、0.991、0.998和0.648、0.719、0.831;在AMI后2～10 h cTnI和CK-MB各指标临界值对应的敏感度分别为90.6%、97.6%、97.7%和54.1%、56.9%、76.9%;特异度分别为87.3%、95.4%、98.5%和87.3%、93.5%、88.1%;AMI发作10 h的患者若cTnI>20.1μg/L时,心肌再梗死与cTnI相关性良好(r=0.74)。结论cTnI在AMI早期诊断和预测再梗死中有一定的应用价值。     

A rapid latex agglutination test for detection of elevated levels of myoglobin in serum and its value in the early diagnosis of acute myocardial infarction

A latex agglutination test for detection of elevated levels of myoglobin in serum has been studied, and its clinical value in diagnosis of acute myocardial infarction (AMI) has been evaluated on a retrospective material of fifty-five patients consecutively admitted to hospital on suspicion for AMI within 4 h after onset of symptoms. The analysis time was less than 10 min. There was no evidence of interference with other related proteins, as judged from analysis of sera with high content of aspartate and alanine aminotransferase, lactate dehydrogenase and creatine kinase, nor was the test sensitive to haemolysis. However, unspecific agglutination was seen with some sera containing a high concentration of rheumatoid factors. In sera with known concentrations of myoglobin, quantitated by a radioimmunoassay, the test was negative in all sera below 80 micrograms/l (n = 187), and positive in all sera above 140 micrograms/l (n = 209). In the range 80-140 micrograms/l the latex test could be either positive or negative (n = 105). The day-to-day reproducibility was high in the ranges below 80 micrograms/l and above 140 micrograms/l, but range 80-140 micrograms/l. In the diagnosis of AMI the predictive value of a positive result was 0.64, and the predictive value of a negative result was 1.0. The latex agglutination test is therefore clinically useful as an emergency test, and as a very early and sensitive indicator for AMI. Patients with a negative test result during the first 12 h after debut of symptoms can with great certainty be identified as not suffering from AMI, whereas patients with a positive test result should be monitored by further laboratory analyses.     

Heart-fatty acid-binding protein as a marker for early detection of acute myocardial infarction and stroke.

Heart-fatty acid-binding protein (H-FABP) is a small cytosolic protein involved in intracellular fatty acid transport. This protein, highly concentrated in the heart, is quickly released into plasma after myocardial injury. Results from numerous studies suggest that H-FABP is an excellent marker for the early detection of myocardial damage. H-FABP is also expressed in the brain, although in lower concentrations than in the heart. Recent preliminary studies also investigated the usefulness of H-FABP for the diagnosis of acute and chronic neurological disorders. These potential applications of H-FABP in clinical practice are reviewed in this article, with a strong focus on the early diagnosis of acute myocardial infarction and stroke.     

心肌标志物联合检测在急性心肌梗死早期诊断中的应用价值

目的探讨高敏C反应蛋白(hs-CRP)、肌钙蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)联合检测在心肌梗死早期诊断中的应用。方法选取2010年1月至2013年12月荆门市第一人民医院收治的2型糖尿病伴心肌梗死住院患者106例,其中60例具有典型心肌梗死症状的患者纳入对照组,46例不典型心肌梗死患者纳入观察组,动态监测两组患者发病后血清hs-CRP、cTnI、CK-MB水平的变化,并比较不同时间点两组患者各指标水平。结果不同时间点两组患者血清hs-CRP、cTnI、CK-MB水平比较,差异均无统计学意义(P0.05);两组患者血清CK-MB水平均于发病后3~12h开始升高,24~48h达到高峰,3~5d基本恢复正常水平;血清hs-CRP水平于发病后3h开始升高,一直保持高水平,3~5d后开始下降;血清cTnI水平于发病后3~6h开始升高,12~24h达高峰,一直持续高水平,5d后开始下降。结论 CK-MB、hs-CRP及cTnI联合检测有助于心肌梗死的早期诊断,尤其可提高症状不明显患者的诊断率,避免漏诊、误诊。     

Development of a rapid microparticle-enhanced nephelometric immunoassay for serum myoglobin in acute myocardial infarction.

A microparticle-enhanced nephelometric immunoassay was developed for myoglobin quantitation in human serum. It uses rabbit antimyoglobin serum and hydrophilic polyacrylic microparticles covalently coated with baboon myoglobin in a competitive immunoagglutination system. The level of microparticle agglutination is assessed with a specially designed nephelometer. This sensitive (45 ng/ml of myoglobin detected in serum) and accurate (coefficients of variation from 3.0% to 8.2% in precision study and linear recovery of myoglobin in overloaded sera) immunoassay was evaluated with human sera from patients suffering from acute myocardial infarction. Myoglobin levels in patient's serum on admission appeared to be correlated with clinical and biological parameters assessed in emergency wards and later. This new, rapid, and easy microparticle-enhanced nephelometric immunoassay could thus be useful in emergency conditions for the early quantitation of serum myoglobin.     

急性心肌梗死早期生化标志物在AMI早期诊断中的应用

目的研究急性心肌梗死（AMI）早期生化标志物心型脂肪酸结合蛋白（H—FABP）、肌红蛋白（Mb）、C反应蛋白（CRP）在AMI早期诊断中的应用价值，并与肌钙蛋白I（cTnI）比较，为AMI的早期诊断提供更理想的指标。方法观察AMI患者36例，在不同的时间段测定H—FABP、Mb、CRP、cTnI并与40例健康人检测结果进行比较。结果CRP在AMI发生4h后升高，在24h内均有较高水平，敏感性也较高。H—FABP与Mb在AMI发生后1h即开始升高，较CRP提前释放，持续至12h，且敏感性较高。H—FABP特异性高于Mb及CRP。cTnI在AMI发生1h后有阳性枪出，但只有在6h后有较高的检出率，且持续时间较长。结论H—FABP较CRP、Mb、cTnI对早期AMl（特别是6h内）更具诊断价值，cTnI为AMI的确定标志物，早期生化标志物H—FABP与cTnI一起可望成为AMI诊断的重要检测标志物。