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CARDIAC TROPONIN T IS A SENSITIVE, SPECIFIC BIOMARKER OF CARDIAC INJURY IN LABORATORY ANIMALS

机译:心肌肌钙蛋白T是实验室动物心脏损伤的敏感的特定生物标记

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摘要

A reliable serum assay that can discriminate between cardiac and skeletal muscle injury is not available for diagnostic use in laboratory animals. We tested and supported the hypotheses that serum cardiac troponin T (cTnT) was widely applicable in laboratory animals as a biomarker of cardiac injury arising from various causes; that it increased in proportion to severity of cardiac injury; and that it was more cardiospecific than creatine kinase (GM) or lactate dehydrogenase (LD) isozyme activities, In canine and rat models of myocardial infarction, cTnT concentration increased 1,000- to 10,000-fold and was highly correlated with infarct size within 8 h of injury. Serum CR and LD isozymes were substantially less effective biomarkers and, in contrast to cTnT, were ineffective markers in the presence of moderate skeletal muscle injury with resulting serum CK activity >5,000 U/L. Using these animal models, and mouse and ferret models, we also showed cTnT to be an effective biomarker in doxorubicin cardiotoxicosis, traumatic injury, ischemia, and cardiac puncture, Reference range serum concentrations for all species were at the detection limit of the assay, except those for mice, in which they were slightly increased, possibly because mice were used to generate assay monoclonal antibodies. We conclude that cTnT is a powerful biomarker in laboratory animals for the sensitive and specific detection of cardiac injury arising from various causes.
机译:不能区分心脏和骨骼肌损伤的可靠血清测定法不能用于实验室动物的诊断。我们测试并支持了以下假设:血清心肌肌钙蛋白T(cTnT)可作为各种原因引起的心脏损伤的生物标记物而广泛用于实验动物。它与心脏损伤的严重程度成比例地增加;并且它比肌酸激酶(GM)或乳酸脱氢酶(LD)同工酶活性更具心脏特异性。在犬和大鼠心肌梗死模型中,cTnT浓度增加了1,000-10,000倍,并且与梗死面积在8小时内高度相关受伤。与cTnT相比,血清CR和LD同工酶实质上是无效的生物标志物,在存在中度骨骼肌损伤的情况下是无效的标志物,导致血清CK活性> 5,000 U / L。使用这些动物模型以及小鼠和雪貂模型,我们还证明了cTnT是阿霉素心脏毒性,创伤性损伤,局部缺血和心脏穿刺的有效生物标志物,所有物种的参考范围血清浓度均在检测限内,除了它们的小鼠略有增加,可能是因为使用了小鼠来生成测定单克隆抗体。我们得出的结论是,cTnT是实验室动物中强大的生物标记物,可用于敏感和特异地检测各种原因引起的心脏损伤。

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