The specificity of biochemical markers of cardiac damage: a problem solved.

This paper reviews the tissue specificity of cardiac troponin I (cTnl), cardiac troponin T (cTnT) and creatine kinase (CK) MB in human and animal heart and skeletal muscles. Studies reveal that CK-MB can be expressed up to 20% of total CK activity in human skeletal muscle; and therefore is not 100% specific for the heart. One cTnl isoform has been described and shown to be 100% specific for the heart. While one to four cTnT isoforms are expressed in diseased and regenerating human skeletal muscle, these isoforms are not the same as the cTnT isoforms expressed in the human heart and are not detected by the cTnT diagnostic assays used in clinical practice. Representative cases are described demonstrating the role of monitoring cardiac troponins in blood for differentiating false positive CK-MB increases due to skeletal muscle injury. Further, sufficient reactivity and tissue specificity of cTnl and cTnT assays are demonstrated for use as markers of myocardial injury in laboratory animals. Monitoring cTnl and cTnT concentrations in the circulation appears poised as the new standards for detection of myocardial injury.     

Tissue specificity of cardiac troponin I, cardiac troponin T and creatine kinase-MB.

The purpose of the paper is to review the tissue specificity of creatine kinase (CK)-MB, cardiac troponin I (cTnI), and cardiac troponin T (cTnT) in human and animal heart and skeletal muscle. Alterations are described which demonstrate that CK-MB is expressed in human skeletal muscle, and is not 100% specific for the heart. cTnI has been shown to be 100% specific for the heart. While cTnT isoforms are expressed in injured skeletal muscle, they are not detected by the diagnostic assays used in clinical practice. Therefore, cTnI or cTnT challenge CK-MB as the new standards for detection of myocardial injury.     

Cardiac troponin and beta-type myosin heavy chain concentrations in patients with polymyositis or dermatomyositis

Cardiac troponin T (cTnT), cardiac troponin I (cTnI), myosin heavy chains (MHC), myoglobin, creatine kinase (CK), and creatine kinase isoenzyme MB (CKMB), were measured in blood samples from 39 polymyositis (PM) or dermatomyositis (DM) patients without clinical evidence for cardiac involvement to evaluate their clinical usefulness in this patient population. MHC, myoglobin, and CKMB were frequently elevated and correlated with each other and with disease severity. Undetectable cTnI in all but one patient indicated that MHC was released from skeletal muscle, thereby providing the first laboratory evidence of frequent slow-twitch muscle fibre-necrosis in patients with PM or DM. CKMB was elevated in 51%, cTnT in 41%, and cTnI in only 2.5% of patients. cTnI did not correlate with other markers or with disease severity scores. The close correlations found between cTnT and skeletal muscle damage markers and the relationship between cTnT with disease severity without clinical evidence for myocardial damage suggest a release of cTnT from skeletal muscle. The relationship of cTnT with disease severity indicates a possible role of the marker for risk stratification. However, the prognostic values of cardiac troponins and other muscle damage markers in PM/DM patients remain to be compared in prospective outcome trials.     

Correlation of antemortem serum creatine kinase, creatine kinase-MB, troponin I, and troponin T with cardiac pathology

BACKGROUND: Spurious increases in serum troponins, especially troponin T, have been reported in patients with and without acute myocardial syndromes. METHODS: We studied 78 autopsied patients without clinical myocardial infarction (MI) and correlated histologic cardiac findings with antemortem serum creatine kinase (CK), its MB isoenzyme (CK-MB), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). RESULTS: There was no significant myocardial pathology in 15 patients. Cardiac pathologies were in five groups: scarring from previous MI or patchy ventricular fibrosis (n = 9), recent MI (n = 27), healing MI (n = 7), degenerative myocyte changes consistent with congestive heart failure (CHF; n = 12), and other cardiac pathologies (n = 8). The median concentrations in the five groups were not significantly different for either CK or CK-MB. Compared with the no-pathology group, only the MI group was significantly different for cTnI, and the MI and other pathology groups were significantly different for cTnT. For patients with MI, 22%, 19%, 48%, and 65% had increased CK, CK-MB, cTnI, and cTnT, respectively; for CHF and other cardiac pathologies combined, the percentages were 28%, 17%, 22%, and 50%. For patients with increased cTnI, 72% and 28% had MI and other myocardial pathologies, respectively; patients with increased cTnT had 64% and 36%, respectively. Patients without myocardial pathology had no increases in CK-MB, cTnI, or cTnT. CONCLUSIONS: All patients with increased serum CK-MB, cTnI, and cTnT had significant cardiac histologic changes. The second-generation cTnT assay appears to be a more sensitive indicator of MI and other myocardial pathologies than the cTnI assay used in this study.     

血清心肌肌钙蛋白对心肌损伤的临床诊断价值

目的　探讨定量分析肌钙蛋白T(cTnT)、肌钙蛋白I(cTnI)对心肌损伤程度评价的临床意义。方法　对80例心肌梗死患[急性心肌梗死(AMI)50例、陈旧性心肌梗死(OMI)30例]、100例心脏手术患、60例非心脏手术患和20例健康人进行了血清cTnT、cTnI、肌酸激酶同工酶(CK—MB)和肌酸激酶(CK)检测。结果　(1)血清cTnT、cTnI、CK—MB和CK检测心肌损伤的敏感度和特异性分别为cTnT(72.4％，100.0％)、cTnI(81.8％，100.0％)，CK—MB(54.6％，87.5％)和CK(64.8％，62.2％)。(2)AMI和心脏手术组cTnT、cTnI、CK—MB和CK四项指标浓度均显高于正常对照组(P＜0.01)。(3)急性心肌梗死组、心脏手术组3h内cTnT和cTnI阳性检出率分别为(50％，56％)和(44％，45％)，明显高于CK—MB(24％，22％)和CK(20％，28％)；急性心肌梗死组、心脏手术组5d后cTnT和cTnI阳性检出率为(70％，66％)和(66％，61％)，而CK—MB仅为(4％，6％)，CK仅为(8％，10％)。结论　血清cTnT、cTnI能确切反映急性心肌梗死、心脏手术等心肌损伤程度，具有较宽的诊断窗口时间，是心肌损伤较敏感和特异的血清标志物。     

Laboratory diagnosis of patients with acute chest pain.

The enzyme activities of creatine kinase (CK), its isoenzyme MB (CK-MB) and of lactate dehydrogenase isoenzyme 1 (LD-1) have been used for years in diagnosing patients with chest pain in order to differentiate patients with acute myocardial infarction (AMI) from non-AMI patients. These methods are easy to perform as automated analyses, but they are not specific for cardiac muscle damage. During the early 90's the situation changed. First creatine kinase MB mass (CK-MB mass) replaced the measurement of CK-MB activity. Subsequently cardiac-specific proteins troponin T (cTnT) and troponin I (cTnI) appeared on the scene, displacing LD-1 analysis. However, troponin concentrations in blood increase only from four to six hours after onset of chest pain. Therefore a rapid marker such as myoglobin, fatty acid binding protein or glycogen phosphorylase BB could be used in early diagnosis of AMI. On the other hand, CK-MB isoforms alone may also be useful in rapid diagnosis of cardiac muscle damage. Myoglobin, CK-MB mass, cTnT and cTnI are nowadays widely used in diagnosing patients with acute chest pain. Myoglobin is not cardiac-specific and therefore requires supplementation with some other analyses such as troponins to support the myoglobin value. Troponins are very highly cardiac-specific. Only the sera of some patients with severe renal failure, which requires hemodialysis, have elevated cTnT and/or cTnI without there being any evidence of cardiac damage. On the other hand, the latest studies have shown that elevated troponin levels in sera of hemodialysis patients point to an increased risk of future cardiac events in a similar manner to the elevated troponin values in sera of patients with unstable angina pectoris. In addition, the bedside tests for cTnT and cTnI alone or together with myoglobin and CK-MB mass can be used instead of quantitative analyses in the diagnosis of patients with chest pain. These rapid tests are easy to perform and they do not require expensive instrumentation. For routine clinical laboratory practice we suggest that in diagnosis of patients with chest pain, myoglobin and CK-MB mass measurements should be performed whenever they are requested (24 h/day) and cTnT or cTnI on admission to the hospital and then 4-6 and 12 hours later.     

Cardiac troponin I and troponin T: recent players in the field of myocardial markers.

The troponin (Tn) complex consists of three subunits referred to as TnT, TnI and TnC. Myocardium contains TnT and TnI isoforms which are not present in skeletal muscles and which can be separated from the muscular isoforms by immunological techniques. Using commercially available immunoassays, clinical laboratories are able to determine cardiac TnT and TnI (cTnT and cTnI) quickly and reliably as classical cardiac markers. After acute myocardial infarction, cTnT and cTnI concentrations start to increase in serum in a rather similar way than CK-MB, but return to normal after longer periods of time (approximately one week). Because of their excellent cardiac specificity, Tn subunits appear ideally suited for the differential diagnosis of myocardial and muscular damage, for example in noncardiac surgery patients, in patients with muscular trauma or with chronic muscular diseases, or after intense physical exercise. cTnT and cTnI may also be used for detecting evidence of minor myocardial damage: therefore they have found new clinical applications, in particular risk stratification in patients with unstable angina. In spite of the possible reexpression of cTnT in human skeletal muscles, and of the lack of standardization of cTnI assays, Tn subunits are not far to meet the criteria of ideal markers for acute myocardial injury. Only an insufficient sensitivity in the first hours following the acute coronary syndroms requiries to maintain an early myocardial marker in the cardiac panel for routine laboratory testing.     

心肌肌钙蛋白I、肌钙蛋白T、肌酸激酶同工酶MB早期诊断 急性心肌梗死敏感性及特异性比较分析

目的 探讨心肌肌钙蛋白Ⅰ（cTnI)、 肌钙蛋白T（cTnT)、 肌酸激酶同工酶MB（CK－MB）早期诊断急性心肌梗死的临床应用价值。方法 对60例急性心肌梗死（AMI）和40例不稳定型心绞痛（UA）患者的同一血样标本检测cTnI、cTnT、CK－MB3项指标,分别进行两组间比较,并对 AMI组和UA组各指标作对比分析。结果 cTnI、cTnT早期诊断急性心肌梗死灵敏度高于CK－MB,阳性率分别为63.3%、46.7%、18.3％,P＜0.01;cTnI和cTnT无显著差别,P＞0.05;cTnI、cTnT、CK－MB特异性相当。结论 心肌肌钙蛋白I和肌钙蛋白T对于AMI的早期诊断具有较高灵敏度和较强特异性,是心肌损伤特异笥标志物,cTnI检测方便、快捷、准确,具有较好的临床价值。     

肌钙蛋白Ⅰ与CK-MB联合检测对急性心肌梗死的诊断价值

目的探讨肌钙蛋白I(cTnI)与CK-MB联合检测对急性心肌梗死(AM I)的临床诊断价值。方法采用罗氏电发光2010自动生化分析仪和日立7180生化分析仪,测定62例AM I患者、50例健康体检者血清的cTnI、肌酸激酶(CK)和CK-MB,并对结果进行统计学分析。结果AM I组血清cTnI、CK和CK-MB高于正常对照组(P<0.01)。cTnI与CK-MB联合检测阳性率为96.7%,高于前三者,且动态检测对早期AM I敏感性更高、阳性持续时间更长。结论肌钙蛋白I与CK-MB联合检测能提高早期急性心肌梗死的检出率,具有更宽的诊断时间窗。     

心肌标志物作用的系统分析

目的：获取心肌生化标记物的最佳应用证据。方法：查循、浏览对心肌肌酸激酶同工酶MB（CK－MB）、肌红蛋白、心肌肌钙蛋白T（cTnT）和心肌肌钙蛋白I（cTnI）用于诊断心肌梗塞（MI）和对急性冠状动脉综合症分级的系统评价和Meta－分析的文献资料。结果：在症状发生后的12－48小时采样分析CK－MB质量对于诊断MI的临床灵敏度和牧场划性分别是98．8％和89．6％。肌红蛋白有高的阴性预示值,在症状发生后的2－6小时采样分析有高的临床灵敏度。在症状发生后的12采样cTnI,诊断MI的临床灵敏度和特异性分别是98．2％和68．8％,其临床特异性降低与检测到微小心肌受损有关。结论：cTnT和cTnI比CK－MB对诊断心肌梗死和预测急性冠状动脉综合症危险性更有价值。     

Effects of implantable cardioverter defibrillator implantation and shock application on biochemical markers of myocardial damage

BACKGROUND: Implantable cardioverter defibrillator (ICD) implantation is a common approach in patients at high risk of sudden cardiac death. To check for normal function, it is necessary to test the ICD. For this purpose, repetitive induction and termination of ventricular fibrillation by direct current shocks is required. This may lead to minor myocardial damage. Cardiac troponin T (cTnT) and I (cTnI) are specific markers for the detection of myocardial injury. Because these proteins usually are undetectable in healthy individuals, they are excellent markers for detecting minimal myocardial damage. The objective of this study was to evaluate the effect of defibrillation of induced ventricular fibrillation on markers of myocardial damage. METHODS: This study included 14 patients who underwent ICD implantation and intraoperative testing. We measured cTnT, cTnI, creatine kinase MB (CK-MB) mass, CK activity, and myoglobin before and at definite times after intraoperative shock application. RESULTS: Depending on the effectiveness of shocks and the energy applied, the cardiac-specific markers cTnT and cTnI, as well as CK-MB mass, showed a significant increase compared with the baseline value before testing and peaked for the most part 4 h after shock application. In contrast, the increases in CK activity and myoglobin were predominantly detectable in patients who received additional external shocks. CONCLUSIONS: ICD implantation and testing leads to a short release of cardiac markers into the circulation. This release seems to be of cytoplasmic origin and depends on the number and effectiveness of the shocks applied.     

心肌损伤标志物在非Q波型急性心肌梗死早期诊断中的应用

目的探讨心肌损伤标志物在非Q波型急性心肌梗死（AMI）早期诊断中的应用,减少非Q波型AMI误诊的机会。方法通过单克隆金标志双抗免疫渗滤快速分析法,动态观测心肌标志物在非Q波型AMI时的敏感性、特异性、漏诊率及诊断符合率。结果心肌肌钙蛋白I（cTnI）、肌红蛋白（Myo）、肌酸激酶-同工酶质量（CK-MB mass）对非Q波型AMI的相对敏感性为38．3％～85．1％,诊断符合率为62．1％～82．8％,均随时间增加逐渐增高;相对特异性为75．0％～100％,漏诊率为14．9％～61．7％,均随时间增加降低;心肌肌钙蛋白T（cTnT）、cTnI在不同时间均优于CK-MB mass,Myo相对敏感性在6h后迅速从85．1％下降至44．7％、12．8％,漏诊率在6h只有14．9％。结论cTnT、cTnI、Myo、CK-MBmass对非Q波型AMI的早期、快速诊断具有一定价值,其临床应用将减少非Q波型AMI误诊的机会。     

Cardiac troponin T and creatine kinase MB are not increased in exterior oblique muscle of patients with renal failure

BACKGROUND: Serum cardiac troponin T (cTnT) concentrations may be increased in patients with renal dysfunction without evidence of cardiac damage, as assessed by conventional methods. It has been suggested that these positive measurements result from the expression in skeletal muscle of fetal isoforms of cTnT, which are detected by the cTnT immunoassay. METHODS: Skeletal muscle (exterior oblique) biopsies were taken from healthy living kidney donors (n = 5) and transplant recipients (n = 19). The amounts of cTnT and creatine kinase (CK) isoenzymes in skeletal muscle of healthy controls were compared with those in patients with renal failure (Wilcoxon-Mann-Whitney test). cTnT was measured quantitatively by a second-generation assay, with a limit of detection of 1 microg/g of protein, and qualitatively by immunohistochemistry and immunoblotting. CK-MB was measured by quantitative electrophoresis. RESULTS: Minute quantities of cTnT were detected in 2 of the 5 (40%) control samples and 9 of the 19 (47%) renal failure samples, respectively, at mean concentrations of <5 microg/g of protein for both subject groups. This was <1/6000th that found in heart muscle. There was no significant difference in cTnT or CK-MB content in skeletal muscle between healthy controls and patients with renal failure. Increased serum cTnT did not predict detectable cTnT in skeletal muscle. cTnT was not detected qualitatively by immunoblotting or immunohistochemistry in any skeletal muscle samples. CONCLUSIONS: Uremia does not affect the content of cTnT or CK-MB in exterior oblique muscle, suggesting that cTnT detected in serum from patients with renal failure does not originate from skeletal muscle.     

Clinical and experimental results on cardiac troponin expression in Duchenne muscular dystrophy

BACKGROUND: Because of controversial earlier studies, the purpose of this study was to provide novel experimental and additional clinical data regarding the possible reexpression of cardiac troponin T (cTnT) in regenerating skeletal muscle in Duchenne muscular dystrophy (DMD). METHODS: Plasma from 14 patients (mean age, 7.5 years; range, 5.7-19.4 years) with DMD was investigated for creatine kinase (CK), the CK MB isoenzyme (CKMB), cTnT and cardiac troponin I (cTnI), and myoglobin. cTnT concentrations were measured by an ELISA (second-generation assay; Roche) using the ES 300 Analyzer. cTnI, myoglobin, and CKMB were measured by an ELISA using the ACCESS System (Beckman Diagnostics). Troponin isoform expression was studied by Western blot analysis in remnants of skeletal muscle biopsies of three patients with DMD and in an animal model of DMD (mdx mice; n = 6). RESULTS: There was no relation of cTnT and cTnI to clinical evidence for cardiac failure. cTnI concentrations remained below the upper reference limit in all patients. cTnT was increased (median, 0.11 microg/L; range, 0.06-0.16 microg/L) in 50% of patients. The only significant correlation was found for CK (median, 3938 U/L; range, 2763-5030 U/L) with age (median, 7.5 years; range, 6.8-10.9 years; r = -0.762; P = 0.042). Western blot analysis of human or mouse homogenized muscle specimens showed no evidence for cardiac TnT and cTnI expression, despite strong signals for skeletal muscle troponin isoforms. CONCLUSIONS: We found no evidence for cTnT reexpression in human early-stage DMD and in mdx mouse skeletal muscle biopsies. Discrepancies of cTnT and cTnI in plasma samples of DMD patients were found, but neither cTnT nor cTnI plasma concentrations were related with other clinical evidence for cardiac involvement.     

Diagnostic utility of new immunoassays for the cardiac markers cTnI, myoglobin and CK-MB mass

OBJECTIVES: We investigated the diagnostic value of a new system, the Innotrac Aio! immunoassays for troponin, myoglobin and CK-MB, in 270 samples from patients with ACS, after bypass surgery (CABG) or with stable heart failure in comparison to the respective Roche assays. RESULTS: The values of the cardiac markers assessed by the respective assays correlated (cTnT/cTnI Rho = 0.94, myoglobin Rho = 0.87, CK-MB Rho = 0.84). If values were dichotomised, we found a high concordance of test positive and negative classified patients by troponins with the respective assays. CONCLUSION: There is strong evidence that the Innotrac Aio! system for cTnI measurement can be used reliably.     

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.     

Comparison of cardiac troponin T and troponin I assays--implications of analytical and biochemical differences on clinical performance

The usefulness of cardiac troponins for detection of myocardial cell necrosis and risk stratification has been established beyond doubt. Cardiac troponin testing is a key diagnostic element for the diagnosis and management of patients with acute coronary syndromes without ST segment elevation and is increasingly used in non-coronary diseases to indicate prognostically important cardiac damage. Given the biochemical and analytical differences of cTnT and cTnI there is ongoing controversy regarding the comparability and clinical performance of cTnT and cTnI. cTnT and cTnI are both expressed in cardiomyocytes but differ with respect to biochemical and analytical characteristics. While minor differences of analytical precision or biochemical properties are not relevant for diagnosis and management of patients with acute coronary syndromes and most diseases with non-coronary related elevations of cardiac troponins, these differences may be amplified in patients with chronic renal failure. In fact, recent studies in patients with end-stage renal disease under chronic hemodialysis have readdressed the issue whether cTnT and cTnI are really comparable. The present review will provide a state-of-the-art overview on the performance of cardiac troponins in acute coronary disease and other clinical conditions.     

Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats,and their relationship with echocardiographic and histological findings

BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.     

Role of cardiac troponin I in the evaluation of myocardial injury

Cardiac troponin I (cTnI) is highly specific for cardiac muscle. In this study, we compared the utility of CK and CK-MB index versus cTnI in the assessment of myocardial infarction in 155 patients being evaluated for myocardial damage. As a cardiac marker for MI, Troponin I seems to be superior to CK-MB. In the subset of patients with renal disease, cTnI has definite advantages over CK-MB. In addition, the use of cTnI has the potential to replace the measurement of lactate dehydrogenase isoenzymes. J. Clin. Lab. Anal. 12:276–279, 1998. © 1998 Wiley-Liss, Inc.