Grund F, Sommerschild H T, Kirkebøen K A, Ilebekk A
Institute for Experimental Medical Research, University of Oslo, Oslo, Norway.
J Mol Cell Cardiol. 1997 Nov;29(11):3067-79. doi: 10.1006/jmcc.1997.0521.
We tested the hypothesis that ischaemic preconditioning reduces pre-ischaemic energy demand and thereby reduces the energy supply-demand mismatch imposed by coronary artery occlusion. Experiments were performed in 52 open chest pigs anaesthetised with sodium pentobarbital. One or two cycles, each of 10 min LAD occlusion followed by 30 min reperfusion, served as the preconditioning stimuli. The degree of protection was evaluated by measuring infarct size (tetrazolium stain) as percentage of area at risk (fluorescent particles) after 45 min LAD occlusion followed by 2 h reperfusion. One preconditioning cycle reduced regional myocardial oxygen consumption (MVO2) by 15+/-3% (P<0.05), whereas two cycles of preconditioning reduced MVO2 by 25+/-3% (P<0.05 v one cycle). This reduction was probably due to reduced energy demand, as both coronary blood flow and arteriovenous oxygen differences decreased, without lactate release or reduction in peak hyperaemic flow response. Energy requirements were most likely also reduced during ischaemia since repayment of flow debt after the second ischaemic period was 33+/-7% less than after the first ischaemic period (P<0.001). One preconditioning cycle reduced infarct size from 58+/-3% of area at risk to 40+/-5% (P<0.05), whereas two cycles of preconditioning reduced infarct size to 15+/-4% of area at risk (P<0.05 v one cycle). We conclude that preconditioning with ischaemia reduces energy consumption in a graded pattern. This effect may contribute to the graded protective effect of ischaemic preconditioning.
缺血预处理可降低缺血前的能量需求,从而减少冠状动脉闭塞所导致的能量供需失衡。实验在52只戊巴比妥钠麻醉的开胸猪身上进行。一个或两个预处理周期,每个周期包括10分钟的左前降支闭塞,随后30分钟的再灌注,作为预处理刺激。在左前降支闭塞45分钟后再灌注2小时,通过测量梗死面积(四氮唑染色)占危险区域面积(荧光颗粒)的百分比来评估保护程度。一个预处理周期可使局部心肌耗氧量(MVO2)降低15±3%(P<0.05),而两个预处理周期可使MVO2降低25±3%(与一个周期相比,P<0.05)。这种降低可能是由于能量需求减少,因为冠状动脉血流量和动静脉氧差均降低,且无乳酸释放或充血峰值血流反应降低。缺血期间能量需求很可能也降低了,因为第二个缺血期后的血流亏欠偿还比第一个缺血期少33±7%(P<0.001)。一个预处理周期可使梗死面积从危险区域的58±3%降至40±5%(P<0.05),而两个预处理周期可使梗死面积降至危险区域的15±4%(与一个周期相比,P<0.05)。我们得出结论,缺血预处理以分级模式降低能量消耗。这种效应可能有助于缺血预处理的分级保护作用。