Ischemic preconditioning: Infarct size is a more reliable endpoint than functional recovery

Ischemic preconditioning: Infarct size is a more reliable endpoint than functional recovery
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DOI:
10.1007/s00395-003-0427-6
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发表时间:
2003-09-01
影响因子:
9.5
通讯作者:
Moolman, JA
Moolman, JA
中科院分区:
医学1区
文献类型:
--
作者:
Lochner, A;Genade, S;Moolman, JA

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研究人员使用不同的动物种类、实验模型、方案和终点获得了有争议的结果,这阻碍了对预处理诱导的心脏保护机制的研究。本研究的目的是评价预处理中灌注模型(逆行与工作)、梗死面积和缺血严重程度(局部与全局)以及终点(功能恢复与梗死面积)的作用。离体灌注大鼠心脏预处理3 × 5分钟的全球缺血,然后不同时期的区域或全球缺血和再灌注。缺血预处理的工作心脏增加功能恢复后25-35分钟的整体缺血,而逆行灌注心脏没有显着改善(除了30分钟后的整体缺血)。此外,在后一组中观察到的再灌注过程中功能表现的百分比降低明显低于工作心脏。心脏也受到局部缺血,灌注逆行或工作模式和梗死面积确定。局部缺血的工作,以及逆行灌注的心脏时,预处理表现出显着增加功能恢复后35分钟缺血。与整体缺血相比,局部缺血心脏的机械性能恢复百分比不受灌注模式的影响。预处理的工作心脏造成了显着减少梗死面积后30和35分钟缺血。然而,预处理的逆行灌注心脏显示了一个显着的下降,梗死面积后35分钟局部缺血。总之,灌注模式对功能恢复的影响取决于缺血的大小和严重程度。它还影响缺血时间,在此时间内,通过预先预处理,在逆行灌注心脏中发生梗死面积减少。
The search for the mechanism of preconditioning-induced cardioprotection has been hampered by controversial results obtained by workers using different animal species, experimental models, protocols and end-points. The aim of this study was to evaluate the role of the perfusion model (retrograde vs working), the infarct size and severity of ischaemia (regional vs global) as well as the endpoint (functional recovery vs; infarct size) in preconditioning. The isolated perfused rat heart was preconditioned by 3 x 5 min global ischaemia, followed by different periods of regional or global ischaemia and reperfusion. Ischaemic preconditioning of working hearts resulted in increased functional recovery after 25-35 min global ischaemia, while retrogradely perfused hearts showed no significant improvement (except after 30 min global ischaemia). In addition, the percentage reduction in functional performance during reperfusion observed in the latter group was significantly less than in working hearts. Hearts were also subjected to regional ischaemia, perfused in either retrograde or working mode and infarct size determined. Regionally ischaemic working as well as retrogradely perfused hearts when preconditioned showed a significant increase in functional recovery after 35 min ischaemia only. In contrast to global ischaemia, the percentage recovery in mechanical performance of regionally ischaemic hearts was not affected by the mode of perfusion. Preconditioning of working hearts caused a significant reduction in infarct size after both 30 and 35 min ischaemia. However, preconditioned retrogradely perfused hearts showed a significant decline in infarct size after 35 min regional ischaemia only. In conclusion, the effect of the perfusion mode on functional recovery is dependent on the size and severity of ischaemia. It also affects the ischaemic time at which infarct size reduction by prior preconditioning occurs in the retrogradely perfused heart.