Bleuel H, Deschl U, Bertsch T, Bölz G, Rebel W
Boehringer Mannheim GmbH, Department of Experimental Toxicology, University of Heidelberg, Germany.
Exp Toxicol Pathol. 1995 May;47(2-3):121-7. doi: 10.1016/S0940-2993(11)80297-6.
A cardioselective parameter has been available for about 2 years since the development by KATUS of an immunoassay for cardiac Troponin T (TnT). The major advantages of this TnT assay are its cardiospecificity and its sensitivity. The parameters usually determined in toxicity studies in rats to detect alterations in the myocardial cells, e.g. aspartate aminotransferase (ASAT), creatinine kinase (CK) and lactate dehydrogenase (LDH), are either of low sensitivity in this species or give falsely high results as the consequence of stress or haemolysis. We therefore investigated in the present study how well Troponin T, determined with the ELISA Troponin T from Boehringer Mannheim, can detect experimentally induced myocardial lesions in rats. In order to achieve hypoxic damage of the cardiomyocytes in these experiments in rats, male Sprague-Dawley rats were given two doses of 4 mg/kg isoprenaline each (Aludrin from Boehringer Ingelheim, FRG) subcutaneously. The second dose was given 7 h after the start of the experiment. Serum samples were analysed for Troponin T (TnT) levels and, for comparison, aspartate aminotransferase (ASAT), creatine kinase (CK), and lactate dehydrogenase (LDH). Histological examinations of the heart muscle were performed 24 and 96 h after the first injection. As expected, histological examinations of the isoprenaline-treated animals revealed marked myofibrillic degeneration of the myocardium 24 h after the first injection. Markedly elevated serum TnT levels (up to 7.9 ng/ml) were already evident in these animals after 6 h. TnT values decreased with time, but were still statistically significant after 48 h. Of the well-established indicators for diagnosing myocardial infarction, only ASAT showed transient statistically significant increases over 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
自卡图斯公司开发出心肌肌钙蛋白T(TnT)免疫测定法以来,一种心脏选择性参数已经问世约两年了。这种TnT测定法的主要优点是其心脏特异性和敏感性。在大鼠毒性研究中通常用于检测心肌细胞变化的参数,如天冬氨酸转氨酶(ASAT)、肌酸激酶(CK)和乳酸脱氢酶(LDH),在该物种中要么敏感性较低,要么由于应激或溶血而给出错误的高结果。因此,我们在本研究中调查了使用勃林格曼海姆公司的ELISA TnT测定的肌钙蛋白T能多好地检测大鼠实验性诱导的心肌损伤。为了在这些大鼠实验中造成心肌细胞的缺氧损伤,给雄性斯普拉格-道利大鼠皮下注射两剂每剂4mg/kg的异丙肾上腺素(来自德国勃林格殷格翰公司的爱纳灵)。第二剂在实验开始后7小时注射。分析血清样本中的肌钙蛋白T(TnT)水平,并作为比较分析天冬氨酸转氨酶(ASAT)、肌酸激酶(CK)和乳酸脱氢酶(LDH)。在第一次注射后24小时和96小时对心肌进行组织学检查。正如预期的那样,对用异丙肾上腺素处理的动物的组织学检查显示,第一次注射后24小时心肌出现明显的肌原纤维变性。这些动物在6小时后血清TnT水平已经明显升高(高达7.9ng/ml)。TnT值随时间下降,但在48小时后仍具有统计学意义。在诊断心肌梗死的公认指标中,只有ASAT在24小时内显示出短暂的统计学显著升高。(摘要截断于250字)