Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion
Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion
复制标题
DOI：
10.1152/ajpheart.00711.2002
复制
发表时间：
2003-02-01
影响因子：
4.8
通讯作者：
Stowe, DF
中科院分区：
文献类型：
--
作者：
Kevin, LG;Camara, AKS;Stowe, DF
活性氧簇(ROS)被认为与触发心脏缺血预适应(IPC)有关。长时间缺血再灌注时ROS生成减少可能是IPC保护作用的部分原因。在心脏模型中，这些争论要么基于ROS清除剂消除IPC诱导的保存的效果，要么基于氧化产物对再灌注的测量。用荧光分光光度法和荧光探针二氢乙锭(DHE)测定细胞内超氧阴离子自由基(O-2(-))。在豚鼠离体心上连续灌胃，检测IPC和O-2(-)的作用。清除剂锰(III)四(4-苯甲酸)氯化物(MnTBAP)对O-2(-)的作用。形成贯穿于预适应(PC)、缺血30分钟和再灌流60分钟(I/R)阶段。IPC表现为收缩功能的改善和梗塞的减少；MnTBAP取消了这些作用。短暂的PC脉冲增加了O-2(-)。在缺血期，而不是再灌注期。O-2(-)。缺血1min内升高35%，20min时进一步升高至95%，再灌流时缓慢下降。在IPC组，O-2(-)。在指数缺血时，其升高幅度不超过35%，在再灌流时也不增加，这些作用可被MnTBAP消除。我们的结果直接证明了在IPC和I/R期间细胞内ROS是如何增加的，并阐明了ROS在IPC的触发和调节中的作用。
Reactive oxygen species (ROS) are believed to be involved in triggering cardiac ischemic preconditioning (IPC). Decreased formation of ROS on reperfusion after prolonged ischemia may in part underlie protection by IPC. In heart models, these contentions have been based either on the effect of ROS scavengers to abrogate IPC-induced preservation or on a measurement of oxidation products on reperfusion. Using spectrophotofluorometry at the left ventricular wall and the fluorescent probe dihydroethidium (DHE), we measured intracellular ROS superoxide (O-2(-).) continuously in isolated guinea pig heart and tested the effect of IPC and the O-2(-). scavenger manganese( III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) on O-2(-). formation throughout the phases of preconditioning (PC), 30-min ischemia and 60-min reperfusion (I/R). IPC was evidenced by improved contractile function and reduced infarction; MnTBAP abrogated these effects. Brief PC pulses increased O-2(-). during the ischemic but not the reperfusion phase. O-2(-). increased by 35% within 1 min of ischemia, increased further to 95% after 20 min of ischemia, and decreased slowly on reperfusion. In the IPC group, O-2(-). was not elevated over 35% during index ischemia and was not increased at all on reperfusion; these effects were abrogated by MnTBAP. Our results directly demonstrate how intracellular ROS increase in intact hearts during IPC and I/R and clarify the role of ROS in triggering and mediating IPC.