Lochner A, Genade S, Moolman J A
Department of Medical Physiology, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, Republic of South Africa.
Basic Res Cardiol. 2003 Sep;98(5):337-46. doi: 10.1007/s00395-003-0427-6. Epub 2003 Jul 24.
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 endpoints. 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.
使用不同动物物种、实验模型、方案和终点的研究人员所获得的相互矛盾的结果，阻碍了对预处理诱导心脏保护机制的探索。本研究的目的是评估灌注模型（逆行灌注与工作模式灌注）、梗死面积以及缺血的严重程度（局部缺血与全心缺血），还有终点指标（功能恢复与梗死面积）在预处理中的作用。将离体灌注大鼠心脏进行3次5分钟全心缺血预处理，随后进行不同时长的局部或全心缺血及再灌注。工作模式心脏的缺血预处理导致在25 - 35分钟全心缺血后功能恢复增加，而逆行灌注心脏则未显示出显著改善（30分钟全心缺血后除外）。此外，后一组在再灌注期间观察到的功能表现降低百分比明显低于工作模式心脏。心脏还接受局部缺血处理，分别以逆行或工作模式灌注，并测定梗死面积。局部缺血的工作模式心脏以及逆行灌注心脏在预处理后仅在35分钟缺血后功能恢复有显著增加。与全心缺血不同，局部缺血心脏机械性能的恢复百分比不受灌注模式的影响。工作模式心脏预处理在30分钟和35分钟缺血后均导致梗死面积显著减小。然而，预处理的逆行灌注心脏仅在35分钟局部缺血后梗死面积显著减小。总之，灌注模式对功能恢复的影响取决于缺血的面积和严重程度。它还影响逆行灌注心脏中通过预先预处理使梗死面积减小所发生的缺血时间。
