Dickson E W, Blehar D J, Carraway R E, Heard S O, Steinberg G, Przyklenk K
Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
J Mol Cell Cardiol. 2001 Sep;33(9):1751-6. doi: 10.1006/jmcc.2001.1436.
We have shown that the cardioprotective benefits of ischemic preconditioning (PC) can be transferred from PC to virgin acceptor hearts via coronary effluent transfusion, implicating the presence of hormonal preconditioning factor(s). Using isolated buffer-perfused rabbit hearts, our aims were to: (1) determine whether the protective factor(s) could be concentrated and recovered by reverse phase chromatography and (2) whether opioid receptor activation contributes to this transferred cardioprotection. Material released into the coronary effluent during PC ischemia/reperfusion or normoxic perfusion was concentrated by reverse phase chromatography. In phase one, hearts received no intervention (controls), PC ischemia, concentrate generated from normoxic hearts (normoxic acceptors) or concentrate from PC hearts (PC acceptors). All hearts underwent 40 min of global ischemia, and area of necrosis (AN) was delineated by tetrazolium staining. In phase two, three additional groups of hearts (control, PC and PC acceptors) received the opioid antagonist naloxone (2 microM) throughout the intervention phase. Treatment with normoxic concentrate had no effect on infarct size: (AN: normoxic acceptors 39+/-8%; control 42+/-8%). In contrast, treatment with PC concentrate evoked cardioprotection equivalent to that afforded by conventional PC (AN 19+/-5% and 21+/-6% respectively P<0.05 v control). Naloxone had no effect on infarct size in controls, and did not inhibit preconditioning. However, naloxone abrogated the protection achieved by transfer of PC concentrate (AN: 44+/-7%). These results indicate that PC concentrate evokes a cardioprotective effect via a mechanism requiring an intact opioid receptor system.
我们已经表明，缺血预处理（PC）的心脏保护益处可通过冠状动脉流出液输注从预处理心脏转移至未处理的受体心脏，这暗示了激素预处理因子的存在。利用离体缓冲液灌注兔心脏，我们的目的是：（1）确定保护因子是否可通过反相色谱法浓缩和回收，以及（2）阿片受体激活是否有助于这种转移的心脏保护作用。在PC缺血/再灌注或常氧灌注期间释放到冠状动脉流出液中的物质通过反相色谱法浓缩。在第一阶段，心脏未接受任何干预（对照组）、进行PC缺血处理、接受来自常氧心脏的浓缩物（常氧受体）或来自PC心脏的浓缩物（PC受体）。所有心脏均经历40分钟全心缺血，并用四氮唑染色法勾勒梗死面积（AN）。在第二阶段，另外三组心脏（对照组、PC组和PC受体组）在整个干预阶段接受阿片拮抗剂纳洛酮（2 microM）。用常氧浓缩物处理对梗死面积无影响：（AN：常氧受体39±8%；对照组42±8%）。相比之下，用PC浓缩物处理可诱发与传统PC相当的心脏保护作用（AN分别为19±5%和PC受体21±6%，与对照组相比P<0.05）。纳洛酮对对照组梗死面积无影响，也不抑制预处理。然而，纳洛酮消除了通过转移PC浓缩物所实现的保护作用（AN：44±7%）。这些结果表明，PC浓缩物通过一种需要完整阿片受体系统的机制诱发心脏保护作用。
