Grund F, Gjesdal K, Kirkeboen K A, Ilebekk A
Institute for Experimental Medical Research, University of Oslo, Oslo, Norway.
J Mol Cell Cardiol. 1999 Jul;31(7):1369-80. doi: 10.1006/jmcc.1999.0971.
An explanation of the preconditioning phenomenon must account for the biology of the phenomenon. Here we provide a more thorough characterization of ischaemic preconditioning (IPC), examining temporal characteristics and the importance of the size of area at risk. IPC was induced by two 10-min LAD occlusions separated by 30 min reperfusion in pentobarbital anaesthetized open-chest pigs. The last brief occlusion was followed by either 30 min, 2 h or 4 h of reperfusion. The degree of protection was evaluated by measuring infarct size after either 45 or 60 min LAD occlusion followed by 2 h of reperfusion. To examine the importance of the size of area at risk, the occlusion site on LAD was varied between pigs. IPC followed by 30 min and 2 h of reperfusion reduced infarct size from 58+/-2% of area at risk to 15+/-4% (P<0.05) and 15+/-6% (P<0.05), respectively, by 45 min of LAD occlusion. After 4 h of reperfusion the infarct size-limiting effect of IPC was still prominent when a test ischaemic period of 45 min was used (47+/-5%vs 13+/-1%P<0.05). IPC was paralleled by an increased incidence of ventricular fibrillation during the early phase of the prolonged LAD occlusion after 30 min, 2 h and 4 h of reperfusion. Although no correlation was found between infarct size (as a percentage of area at risk) and area at risk (as a percentage of ventricular weight) in control pigs, a positive correlation was found between these variables in preconditioned pigs. We conclude that the infarct size-limiting effect of IPC lasts at least 4 h and that it is paralleled by profibrillatory effects in open-chest pigs. Furthermore, the infarct size-limiting effect of IPC depends on the size of area at risk, being most pronounced when area at risk is small.
对预处理现象的解释必须考虑该现象的生物学机制。在此，我们对缺血预处理（IPC）进行了更全面的描述，研究了其时间特征以及危险区域大小的重要性。在戊巴比妥麻醉的开胸猪中，通过两次10分钟的左前降支闭塞并间隔30分钟再灌注来诱导IPC。最后一次短暂闭塞后分别进行30分钟、2小时或4小时的再灌注。通过测量在左前降支闭塞45或60分钟后再灌注2小时的梗死面积来评估保护程度。为了研究危险区域大小的重要性，在不同猪之间改变左前降支的闭塞部位。IPC后再灌注30分钟和2小时，在左前降支闭塞45分钟时，梗死面积分别从危险区域的58±2%降至15±4%（P<0.05）和15±6%（P<0.05）。再灌注4小时后，当采用45分钟的试验性缺血期时，IPC的梗死面积限制效应仍然显著（47±5%对13±1%，P<0.05）。在再灌注30分钟、2小时和4小时后，在延长的左前降支闭塞早期，IPC伴随着室颤发生率的增加。虽然在对照猪中未发现梗死面积（占危险区域的百分比）与危险区域（占心室重量的百分比）之间存在相关性，但在预处理猪中发现这些变量之间存在正相关。我们得出结论，IPC的梗死面积限制效应至少持续4小时，并且在开胸猪中伴随着促纤颤效应。此外，IPC的梗死面积限制效应取决于危险区域的大小，当危险区域较小时最为明显。
