Protection against myocardial dysfunction after a brief ischemic period in transgenic mice expressing inducible heat shock protein 70
Protection against myocardial dysfunction after a brief ischemic period in transgenic mice expressing inducible heat shock protein 70
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DOI：
10.1172/jci265
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发表时间：
1998-02-15
影响因子：
15.9
通讯作者：
Dillmann, WH
中科院分区：
文献类型：
--
作者：
Trost, SU;Omens, JH;Dillmann, WH
短暂缺血可导致心肌功能障碍，但无心肌梗死。研究表明，诱导型HSP 70在转基因小鼠心脏中的表达可导致梗死面积减少，但HSP 70是否也能保护短暂缺血后的心肌功能障碍仍不清楚。我们开发了一种小鼠模型，在该模型中，可以在体内暂时性缺血事件之前和之后测量局部心肌功能。此外，在分离的Langendorff心脏中短暂的全脑缺血发作后测定心肌功能。HSP 70阳性小鼠和转基因阴性同窝出生的小鼠经历8分钟的通过阻塞左降支冠状动脉产生的局部心肌缺血，随后再灌注60分钟，局部心外膜应变是反映心肌缺血后心肌功能变化的敏感指标，HSP 70阳性小鼠的最大主应变明显高于转基因阴性小鼠，分别为缺血前的88 ± 6%和58 ± 6同样，在离体Langendorff灌注的心脏中，HSP 70阳性和转基因阴性的同窝小鼠暴露于全脑缺血10分钟和再灌注90分钟，HSP 70转基因心脏显示出更好的心室峰值收缩压保持，因此，我们的结论是HSP70的表达可以保护缺血后的心肌功能障碍，如更好地保护心肌功能所示。
Brief ischemic periods lead to myocardial dysfunction without myocardial infarction, It has been shown that expression of inducible HSP70 in hearts of transgenic mice leads to decreased infarct size, but it remains unclear if HSP70 can also protect against myocardial dysfunction after brief ischemia, To investigate this question, we developed a mouse model in which regional myocardial function can be measured before and after a temporary ischemic event in vivo, In addition, myocardial function was determined after brief episodes of global ischemia in an isolated Langendorff heart, HSP70-positive mice and transgene negative littermates underwent 8 min of regional myocardial ischemia created by occlusion of the left descending coronary artery, followed by 60 min of reperfusion, This procedure did not result in a myocardial infarction, Regional epicardial strain was used as a sensitive indicator for changes in myocardial function after cardiac ischemia, Maximum principal strain was significantly greater in HSP70-positive mice with 88+/-6% of preischemic values vs, 58+/-6% in transgene-negative mice (P < 0.05), Similarly, in isolated Langendorff perfused hearts of HSP70-positive and transgene-negative littermates exposed to 10 min of global ischemia and 90 min of reperfusion, HSP70 transgenic hearts showed a better-preserved ventricular peak systolic pressure, Thus, we conclude that expression of HSP70 protects against postischemic myocardial dysfunction as shown by better preserved myocardial function.