Abstract：
UNASSIGNED: Myotoxicity is an important toxidrome that can occur with envenoming from multiple Australian snake types. Early antivenom administration is an important strategy to reduce the incidence and severity of myotoxicity. The current gold standard biomarker, serum creatine kinase activity, does not rise early enough to facilitate early antivenom administration. Several other skeletal muscle biomarkers have shown promise in other animal models and scenarios. The aim of this study was to examine the predictive values of six skeletal muscle biomarkers in a rat model of Australian snake myotoxicity.
UNASSIGNED: Sprague-Dawley rats were anaesthetised and administered either Pseudechis porphyriacus (red-bellied black snake) or Notechis scutatus (tiger snake) venom, or normal saline via intramuscular injection. Blood samples were collected. Assays were performed for serum creatine kinase skeletal muscle troponin-I concentration, skeletal muscle troponin-C concentration, myoglobin activity, skeletal muscle myosin light chain-1 concentration, and creatine kinase-MM activity. Serum markers were plotted against time, with comparison of area under the concentration (or activity)-time curve. The predictive values of six skeletal muscle biomarkers were examined using receiver operating characteristic curves.
UNASSIGNED: There was no difference in area under the serum creatine kinase activity-time curve between venom and control groups. Serum creatine kinase-MM activity rose early in the venom treated rats, which had a significantly greater area under the serum activity-time curve. No difference in area under the serum concentration-time curve was demonstrated for the other biomarkers. Creatine kinase-MM activity had a superior predictive values than creatine kinase activity at 0-4 hours and 0-10 hours after venom administration, as indicated by area under the receiver operating characteristic curves (95 per cent confidence intervals) of 0.91 (0.78-1.00) and 0.88 (0.73-1.00) versus 0.79 (0.63-0.95) and 0.66 (0.51-0.80).
UNASSIGNED: The limitations of serum creatine kinase activity in early detection of myotoxicity were demonstrated in this rat model.
UNASSIGNED: Serum creatine kinase-MM activity was superior for early detection of Australian myotoxic snake envenoming.
UNASSIGNED: Sprague-Dawley rats were anaesthetised and administered either Pseudechis porphyriacus (red-bellied black snake) or Notechis scutatus (tiger snake) venom, or normal saline via intramuscular injection. Blood samples were collected. Assays were performed for serum creatine kinase skeletal muscle troponin-I concentration, skeletal muscle troponin-C concentration, myoglobin activity, skeletal muscle myosin light chain-1 concentration, and creatine kinase-MM activity. Serum markers were plotted against time, with comparison of area under the concentration (or activity)-time curve. The predictive values of six skeletal muscle biomarkers were examined using receiver operating characteristic curves.
UNASSIGNED: There was no difference in area under the serum creatine kinase activity-time curve between venom and control groups. Serum creatine kinase-MM activity rose early in the venom treated rats, which had a significantly greater area under the serum activity-time curve. No difference in area under the serum concentration-time curve was demonstrated for the other biomarkers. Creatine kinase-MM activity had a superior predictive values than creatine kinase activity at 0-4 hours and 0-10 hours after venom administration, as indicated by area under the receiver operating characteristic curves (95 per cent confidence intervals) of 0.91 (0.78-1.00) and 0.88 (0.73-1.00) versus 0.79 (0.63-0.95) and 0.66 (0.51-0.80).
UNASSIGNED: The limitations of serum creatine kinase activity in early detection of myotoxicity were demonstrated in this rat model.
UNASSIGNED: Serum creatine kinase-MM activity was superior for early detection of Australian myotoxic snake envenoming.
摘要：
■肌毒性是一种重要的毒物，可以随着多种澳大利亚蛇的毒害而发生。早期服用抗血清是降低肌毒性发生率和严重程度的重要策略。当前的黄金标准生物标志物，血清肌酸激酶活性，起得不够早，无法促进抗蛇毒血清的早期管理。其他几种骨骼肌生物标志物在其他动物模型和场景中显示出希望。这项研究的目的是检查澳大利亚蛇肌毒性大鼠模型中六种骨骼肌生物标志物的预测值。
■将Sprague-Dawley大鼠麻醉并给予Pseudechis卟啉（红腹黑蛇）或Notechisscutatus（虎蛇）毒液，或生理盐水肌肉注射。收集血液样品。测定血清肌酸激酶骨骼肌肌钙蛋白-I浓度，骨骼肌肌钙蛋白C浓度，肌红蛋白活性，骨骼肌肌球蛋白轻链-1浓度，和肌酸激酶-MM活性。血清标记物随时间作图,与浓度（或活性）-时间曲线下面积的比较。使用受试者工作特征曲线检查了六种骨骼肌生物标志物的预测值。
■毒液组和对照组的血清肌酸激酶活性-时间曲线下面积没有差异。在毒液处理的大鼠中，血清肌酸激酶-MM活性升高较早，其在血清活性-时间曲线下的面积明显更大。其他生物标志物在血清浓度-时间曲线下的面积没有差异。肌酸激酶-MM活性在毒液给药后0-4小时和0-10小时具有优于肌酸激酶活性的预测值，如受试者工作特征曲线下面积(95%置信区间)为0.91(0.78-1.00)和0.88(0.73-1.00)，与0.79(0.63-0.95)和0.66(0.51-0.80)。
■在该大鼠模型中证明了血清肌酸激酶活性在早期检测肌毒性中的局限性。
■血清肌酸激酶-MM活性优于澳大利亚肌毒性蛇毒的早期检测。
■将Sprague-Dawley大鼠麻醉并给予Pseudechis卟啉（红腹黑蛇）或Notechisscutatus（虎蛇）毒液，或生理盐水肌肉注射。收集血液样品。测定血清肌酸激酶骨骼肌肌钙蛋白-I浓度，骨骼肌肌钙蛋白C浓度，肌红蛋白活性，骨骼肌肌球蛋白轻链-1浓度，和肌酸激酶-MM活性。血清标记物随时间作图,与浓度（或活性）-时间曲线下面积的比较。使用受试者工作特征曲线检查了六种骨骼肌生物标志物的预测值。
■毒液组和对照组的血清肌酸激酶活性-时间曲线下面积没有差异。在毒液处理的大鼠中，血清肌酸激酶-MM活性升高较早，其在血清活性-时间曲线下的面积明显更大。其他生物标志物在血清浓度-时间曲线下的面积没有差异。肌酸激酶-MM活性在毒液给药后0-4小时和0-10小时具有优于肌酸激酶活性的预测值，如受试者工作特征曲线下面积(95%置信区间)为0.91(0.78-1.00)和0.88(0.73-1.00)，与0.79(0.63-0.95)和0.66(0.51-0.80)。
■在该大鼠模型中证明了血清肌酸激酶活性在早期检测肌毒性中的局限性。
■血清肌酸激酶-MM活性优于澳大利亚肌毒性蛇毒的早期检测。
