Xu Z L, Endoh H, Ishihata A, Takahashi E, Doi K
Department of Physiology, Yamagata University School of Medicine, Japan.
J Mol Cell Cardiol. 1998 Nov;30(11):2165-74. doi: 10.1006/jmcc.1998.0771.
Ischemic preconditioning (IPC) in the heart may reduce myocardial energy demand. The present study was undertaken to examine changes in myocardial oxygen consumption (MVO2) during ischemia by IPC in Langendorff perfused rat hearts. We assessed MVO2 during ischemia from the measurement of mitochondrial cyt. aa3 redox state by a two-wavelength reflectance spectrophotometry where T(1/2), the time from the onset of ischemia to the point for half reduction of cyt. aa3, was assumed to represent MVO2. The heart was preconditioned by three cycles of 5 min ischemia plus 5 min reperfusion and then subjected to 30 min global ischemia followed by reperfusion for 30 min. The T(1/2) was significantly longer in the preconditioned heart (30 +/- 6 s, n = 10) than the control heart (14 +/- 5 s, n = 9, P<0.001), indicating a reduction of MVO2 during ischemic period by IPC. The prolongation of T(1/2) was evident after only one IPC episode. When the heart was perfused with high K+ solution to abolish MVO2 for contractions, we still found the prolongation of T1(1/2) in the preconditioned heart (116 +/- 12 s, n = 6) compared to the control heart (86 +/- 10 s, n = 6, P<0.01), suggesting that decrease in contractile activity may be, in part but not completely, responsible for the reduction of MVO2. In contrast, the prolongation of T(1/2) was completely abolished by administration of a NO synthase inhibitor N omega-nitro-L-arginine in the high K+ arrested heart, demonstrating involvement of NO in the reduction of MVO2, presumably by suppression of mitochondrial respiratory chain. In conclusion, IPC reduces MVO2 during ischemia. The reduction of MVO2 in the preconditioned heart may be accounted for by decreased contractile activity and by depression of respiratory chain by NO.
心脏缺血预处理（IPC）可能会降低心肌能量需求。本研究旨在通过Langendorff灌注大鼠心脏模型，研究缺血预处理对缺血期间心肌耗氧量（MVO2）的影响。我们采用双波长反射分光光度法测量线粒体细胞色素aa3的氧化还原状态，以此评估缺血期间的MVO2，其中T(1/2)（即从缺血开始到细胞色素aa3减少一半的时间点）被认为代表MVO2。心脏先经历三个5分钟缺血加5分钟再灌注的循环进行预处理，然后进行30分钟全心缺血，随后再灌注30分钟。预处理组心脏的T(1/2)（30 ± 6秒，n = 10）显著长于对照组心脏（14 ± 5秒，n = 9，P<0.001），表明缺血预处理可降低缺血期间的MVO2。仅一次缺血预处理事件后，T(1/2)的延长就很明显。当心脏用高钾溶液灌注以消除收缩引起的MVO2时，与对照组心脏（86 ± 10秒，n = 6）相比，预处理组心脏的T1(1/2)仍延长（116 ± 12秒，n = 6，P<0.01），这表明收缩活动的降低可能部分但并非完全导致MVO2的降低。相反，在高钾停跳的心脏中，给予一氧化氮合酶抑制剂Nω-硝基-L-精氨酸可完全消除T(1/2)的延长，这表明一氧化氮参与了MVO2的降低，可能是通过抑制线粒体呼吸链实现（推测）。总之，缺血预处理可降低缺血期间的MVO2。预处理心脏中MVO2的降低可能是由于收缩活动的降低以及一氧化氮对呼吸链的抑制作用。
