van den Doel M A, Gho B C, Duval S Y, Schoemaker R G, Duncker D J, Verdouw P D
Laboratory for Experimental Cardiology, Erasmus University Rotterdam, Netherlands.
Cardiovasc Res. 1998 Jan;37(1):76-81. doi: 10.1016/s0008-6363(97)00222-8.
To test the hypothesis that mild hypothermia potentiates the cardioprotection afforded by ischaemic preconditioning so that infarct size limitation can be obtained after coronary artery occlusion (CAO) durations which exceed the cardioprotective range (> 90 min) of either hypothermia or ischaemic preconditioning alone.
Four groups of anaesthetized rats were subjected to different durations of CAO: (i) normothermia (N, 36.5-37.5 degrees C, n = 29), (ii) normothermia + ischaemic preconditioning (N + IP, 15 min CAO followed by 10 min of reperfusion, n = 35), (iii) hypothermia (H, 30-31 degrees C, n = 31) and (iv) hypothermia + ischaemic preconditioning (H + IP, n = 24). Infarct size (IA/AR) was determined after 3 hours of reperfusion using trypan blue to delineate the area at risk (AR) from non-risk region and nitroblue tetrazolium to delineate infarcted area (IA) from viable myocardium.
In N the CAO duration versus infarct size relation had a sigmoid shape with virtually no infarction occurring at 15 min CAO and 56 +/- 5% of the area at risk being infarcted at 30 min CAO reaching a plateau of 71 +/- 2% at 60 min CAO. Hypothermia produced a rightward shift of the relation resulting in an approximately 15 min delay in onset of infarction. Ischaemic preconditioning produced a similar reduction in infarct size (23 +/- 4%) at 30 min CAO compared to hypothermia (13 +/- 3%) but also limited infarct size at 45 min to 36 +/- 3% and at 60 min CAO to 50 +/- 3% suggesting a slowing of infarct progression. Neither intervention limited IA/AR produced by 120 min CAO. In H + IP, combined hypothermia and ischaemic preconditioning resulted in synergistic infarct size reduction so that at 45 min and 60 min CAO IA/AR was reduced to 17 +/- 3% and 23 +/- 3%, respectively, and even at 120 min CAO to 58 +/- 5%, which was significantly smaller than during normothermic control conditions (p < 0.05 vs. N).
Mild hypothermia limited IA/AR modestly but markedly enhanced the cardioprotection afforded by ischaemic preconditioning in the in situ rat heart so that irreversible damage produced by even prolonged coronary artery occlusions was limited.
验证如下假说：轻度低温可增强缺血预处理所提供的心脏保护作用，从而在冠状动脉闭塞（CAO）持续时间超过单独低温或缺血预处理的心脏保护范围（>90分钟）后仍可限制梗死面积。
四组麻醉大鼠接受不同持续时间的CAO：（i）正常体温（N，36.5 - 37.5摄氏度，n = 29），（ii）正常体温 + 缺血预处理（N + IP，15分钟CAO后再灌注10分钟，n = 35），（iii）低温（H，30 - 31摄氏度，n = 31），以及（iv）低温 + 缺血预处理（H + IP，n = 24）。再灌注3小时后，使用台盼蓝区分危险区域（AR）与非危险区域，并用硝基四氮唑蓝区分梗死区域（IA）与存活心肌，以此测定梗死面积（IA/AR）。
在N组中，CAO持续时间与梗死面积的关系呈S形，15分钟CAO时几乎无梗死发生，30分钟CAO时梗死面积占危险区域的56±5%，60分钟CAO时达到71±2%的平台期。低温使该关系右移，导致梗死发生延迟约15分钟。缺血预处理在30分钟CAO时与低温相比梗死面积有类似程度的减小（23±4% vs. 13±3%），但在45分钟CAO时将梗死面积限制为36±3%，60分钟CAO时限制为50±3%，提示梗死进展减缓。两种干预措施均未限制120分钟CAO所产生的IA/AR。在H + IP组中，低温与缺血预处理联合导致梗死面积协同减小，因此在45分钟和60分钟CAO时IA/AR分别降至17±3%和23±3%，甚至在120分钟CAO时降至58±5%，显著小于正常体温对照条件下（与N组相比，p < 0.05）。
轻度低温适度限制了IA/AR，但显著增强了原位大鼠心脏缺血预处理所提供的心脏保护作用，从而即使是长时间冠状动脉闭塞所产生的不可逆损伤也受到限制。
