Skyschally Andreas, Schulz Rainer, Gres Petra, Konietzka Ina, Martin Claus, Haude Michael, Erbel Raimund, Heusch Gerd
Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Cardiovasc Res. 2004 Aug 1;63(2):313-22. doi: 10.1016/j.cardiores.2004.04.003.
After coronary microembolization (ME) adenosine is released from ischemic areas of the microembolized myocardium. This adenosine dilates vessels in adjacent nonembolized myocardium and increases coronary blood flow. For ischemic preconditioning (IP) to protect the myocardium against infarction, an increase in the interstitial adenosine concentration (iADO) prior to the subsequent ischemia/reperfusion is necessary. We hypothesized that the adenosine release after ME is sufficient to increase iADO and protect the myocardium against infarction from subsequent ischemia/reperfusion. We have therefore compared myocardial protection by either coronary microembolization or ischemic preconditioning prior to ischemia/reperfusion.
In anesthetized pigs, the left anterior descending (LAD) was cannulated and perfused from an extracorporeal circuit. In 11 pigs, sustained ischemia was induced by 85% inflow reduction for 90 min (controls). Two other groups of pigs were subjected either to IP (n = 8; 10-min ischemia/15-min reperfusion) or coronary ME (n = 9; i.c. microspheres; 42 microm Ø; 3000 x ml(-1) x min inflow) prior to sustained ischemia. Coronary venous adenosine concentration (vADO) and iADO (microdialysis) were measured. Infarct size was determined after 2-h reperfusion by triphenyl tetrazolium chloride staining.
In pigs subjected to IP, infarct size was reduced to 2.6 +/- 1.1% (mean +/- S.E.M.) vs. 17.0 +/- 3.2% in controls. iADO was increased from 2.4 +/- 1.3 to 13.1 +/- 5.8 micromol x l(-1) during the reperfusion following IP. In pigs subjected to ME, at 10 min after ME, coronary blood flow (38.6 +/- 3.6 to 53.6 +/- 4.3 ml x min(-1)) and vADO (0.25 +/- 0.04 to 0.48 +/- 0.07 micromol x l(-1)) were increased. However, iADO (2.0 +/- 0.5 at baseline vs. 2.3 +/- 0.6 micromol x l(-1) at 10 min after ME) did not increase. Infarct size induced by sustained ischemia following ME (22.5 +/- 5.2%) was above that of controls for any given subendocardial blood flow.
ME released adenosine into the vasculature and increased coronary blood flow. The failure of iADO to increase with ME possibly explains the lack of protection against infarction after ME.
冠状动脉微栓塞（ME）后，腺苷从微栓塞心肌的缺血区域释放。这种腺苷使相邻未栓塞心肌中的血管扩张并增加冠状动脉血流量。为使缺血预处理（IP）保护心肌免于梗死，在随后的缺血/再灌注之前，组织间腺苷浓度（iADO）的增加是必要的。我们假设ME后腺苷的释放足以增加iADO并保护心肌免于随后缺血/再灌注导致的梗死。因此，我们比较了在缺血/再灌注之前通过冠状动脉微栓塞或缺血预处理进行的心肌保护作用。
在麻醉的猪中，将左前降支（LAD）插管并通过体外循环进行灌注。11头猪通过减少85%的血流持续90分钟诱导持续性缺血（对照组）。另外两组猪在持续性缺血之前分别进行IP（n = 8；10分钟缺血/15分钟再灌注）或冠状动脉ME（n = 9；心内注射微球；直径42微米；3000×毫升-1×分钟血流）。测量冠状静脉腺苷浓度（vADO）和iADO（微透析）。在2小时再灌注后通过氯化三苯基四氮唑染色确定梗死面积。
接受IP的猪，梗死面积减少至2.6±1.1%（平均值±标准误），而对照组为17.0±3.2%。在IP后的再灌注期间，iADO从2.4±1.3增加至13.1±5.8微摩尔×升-1。接受ME的猪，在ME后10分钟，冠状动脉血流量（从38.6±3.6增加至53.6±4.3毫升×分钟-1）和vADO（从0.25±0.04增加至0.48±0.07微摩尔×升-1）增加。然而，iADO（基线时为2.0±0.5，ME后10分钟为2.3±0.6微摩尔×升-1）未增加。ME后持续性缺血诱导的梗死面积（22.5±5.2%）在任何给定的心内膜下血流量时均高于对照组。
ME使腺苷释放到血管系统中并增加冠状动脉血流量。iADO未随ME增加可能解释了ME后缺乏对梗死的保护作用。
