Zuurbier C J, Ince C
Department of Anaesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Pflugers Arch. 2002 Mar;443(5-6):908-16. doi: 10.1007/s00424-001-0744-2. Epub 2001 Nov 7.
This study examined whether different durations of ischaemia (I) and reperfusion (R) altered the kinetics of O(2) consumption-to-demand matching and the contribution of changes in calcium and metabolic pathways to possible alterations. The response time of mitochondrial O(2) consumption (t(mito)) to a step in heart rate in isolated rat hearts was used as index for the response time of O(2) consumption-to-demand matching. At baseline, t(mito) was 8.9 +/- 0.4 s for all groups. At 5 min reperfusion, after both reversible (I=5 or I=15 min) or irreversible (I=25 min) ischaemia, matching was accelerated (t(mito) relative to baseline: 53 +/- 8%, 64 +/- 8%, 51+/- 6% and 100 +/- 5% for I=5, 15, 25 min and control). At late reperfusion (>30 min), reversible ischaemia resulted in a slowing of the matching, whereas after irreversible ischaemia t(mito) recovered to control values (156 +/- 16%, 153 +/- 13%, 92 +/- 7%, 114 +/- 6%, for I=5,15, 25 min and control, respectively). High perfusate Ca(2+) mimicked (t(mito): 44 +/- 11%), whereas blocking mitochondrial Ca(2+) uptake attenuated the acceleration observed at early reperfusion (t(mito): 7 +/- 5%). Replacing glucose with substrates used downstream of glycolysis (11 mM lactate or 11 mM pyruvate) abolished the reversible ischaemia-induced slowing of the matching at late reperfusion. It is concluded that I/R-induced changes in the kinetics of O(2) consumption-to demand matching depend critically on the duration of ischaemia and reperfusion. The data indicate that I/R-induced increases in Ca(2+) may, at least partly, explain the faster kinetics at early reperfusion, whereas I/R-induced increases in glycolysis from exogenous glucose result in slower matching of O(2) consumption-to-demand at late reperfusion.
本研究探讨了不同时长的缺血（I）和再灌注（R）是否会改变氧消耗与需求匹配的动力学，以及钙和代谢途径的变化对可能的改变所起的作用。将离体大鼠心脏中线粒体氧消耗（t(mito)）对心率阶跃变化的响应时间用作氧消耗与需求匹配响应时间的指标。在基线时，所有组的t(mito)为8.9±0.4秒。在再灌注5分钟时，无论是可逆性缺血（I = 5或I = 15分钟）还是不可逆性缺血（I = 25分钟）后，匹配均加速（相对于基线的t(mito)：I = 5、15、25分钟和对照组分别为53±8%、64±8%、51±6%和100±5%）。在再灌注后期（>30分钟），可逆性缺血导致匹配减慢，而不可逆性缺血后t(mito)恢复到对照值（I = 5、15、25分钟和对照组分别为156±16%、153±13%、92±7%、114±6%）。高灌注液Ca(2+)可模拟这种情况（t(mito)：44±11%），而阻断线粒体Ca(2+)摄取可减弱再灌注早期观察到的加速现象（t(mito)：7±5%）。用糖酵解下游使用的底物（11 mM乳酸盐或11 mM丙酮酸盐）替代葡萄糖可消除再灌注后期可逆性缺血诱导的匹配减慢。得出的结论是，缺血/再灌注（I/R）诱导的氧消耗与需求匹配动力学变化严重依赖于缺血和再灌注的时长。数据表明，I/R诱导的Ca(2+)增加可能至少部分解释了再灌注早期较快的动力学，而I/R诱导的外源性葡萄糖糖酵解增加导致再灌注后期氧消耗与需求的匹配减慢。
