Yellon D M, Alkhulaifi A M, Browne E E, Pugsley W B
Hatter Institute for Cardiovascular Studies, Department of Academic Cardiology, University College and Middlesex Hospital, London, United Kingdom.
Cardiovasc Res. 1992 Oct;26(10):983-7. doi: 10.1093/cvr/26.10.983.
One of the mechanisms by which ischaemic preconditioning is thought to protect against later prolonged ischaemia is via a reduction in ATP utilisation during ischaemia. The ATP "wastage" that occurs during ischaemia is thought to be due to mitochondrial ATPase activity, which may be prevented in ischaemic preconditioning by the binding of a specific inhibitor protein. As the rat is known to have less inhibitor protein than other species, this study was designed to determine whether the rat heart could be ischaemically preconditioned.
Rats were anaesthetised with pentobarbitone, the chest opened and the hearts ischaemically preconditioned with a 5 min occlusion of the left main coronary artery followed by 10 min reperfusion. The hearts were then subjected to a 45 min occlusion followed by 3 h reperfusion. Control hearts were treated identically but without ischaemic preconditioning. Infarct size was measured using triphenyl tetrazolium and expressed as a percentage of the region at risk, measured with fluorescent particles.
Infarct size as a percent of the risk area in the ischaemically preconditioned group (n = 8) was 31.4(SEM 6.1)%, versus 61.0(4.8)% in control hearts (n = 8) (p < 0.005).
These results show that rat hearts can be ischaemically preconditioned and suggest that the protective mechanism involved in this phenomenon is not mediated through the endogenous inhibition of mitochondrial ATPase. An overall reduction in mitochondrial ATP "wastage" may not be the sole mechanism in the protection seen in ischaemic preconditioning.
缺血预处理被认为可保护机体免受随后长时间缺血影响的机制之一是通过减少缺血期间的ATP利用。缺血期间发生的ATP“浪费”被认为是由于线粒体ATP酶活性所致，在缺血预处理中，一种特异性抑制蛋白的结合可能会阻止这种活性。由于已知大鼠体内的抑制蛋白比其他物种少，本研究旨在确定大鼠心脏是否能进行缺血预处理。
用戊巴比妥麻醉大鼠，打开胸腔，通过阻断左冠状动脉主干5分钟，随后再灌注10分钟对心脏进行缺血预处理。然后使心脏经历45分钟的阻断，随后再灌注3小时。对照心脏接受相同处理，但不进行缺血预处理。使用三苯基四氮唑测量梗死面积，并表示为用荧光颗粒测量的危险区域的百分比。
缺血预处理组（n = 8）梗死面积占危险区域的百分比为31.4（标准误6.1）%，而对照心脏（n = 8）为61.0（4.8）%（p < 0.005）。
这些结果表明大鼠心脏可以进行缺血预处理，并提示这种现象所涉及的保护机制不是通过内源性抑制线粒体ATP酶介导的。线粒体ATP“浪费”的总体减少可能不是缺血预处理中所见保护作用的唯一机制。
