Ritter L S, McDonagh P F
College of Medicine, University of Arizona, Tucson 85724, USA.
Am J Physiol. 1997 Sep;273(3 Pt 2):H1154-65. doi: 10.1152/ajpheart.1997.273.3.H1154.
During early reperfusion after myocardial ischemia, the mechanisms responsible for leukocyte accumulation in the heart are unclear. We examined the effects of reducing coronary blood flow during reperfusion on leukocyte accumulation in coronary capillaries and postcapillary venules. Isolated rat hearts were perfused for 30 min and then subjected to 30 min of 37 degrees C, no-flow ischemia. The deposition of fluorescently labeled leukocytes was observed directly in coronary capillaries and venules using intravital microscopy after 5, 20, and 35 min of reperfusion. Blood cell velocity was measured in venules after 5 min of reperfusion (R5), and shear rate (s-1) was calculated. Four groups were studied: nonischemic control (NIC) hearts and postischemic hearts reperfused at full flow (I/R100) and at 50 and 10% of full flow (I/R50 and I/R10, respectively). In I/R100 hearts, there was a significant increase in leukocyte trapping in capillaries compared with the NIC group (R5: 5.7 +/- 0.6 vs. 2.0 +/- 0.4 leukocytes/capillary field, respectively; P < 0.05). However, the increase in leukocyte adhesion to venules was not statistically significant compared with NIC (R5: 3.2 +/- 0.4 vs. 1.5 +/- 0.6 leukocytes/100-micron venule, respectively; P < 0.2). In I/R50 hearts, a further increase in leukocyte accumulation occurred in the capillaries but not in the venules. However, in I/R10 hearts, there was a statistically significant increase in both capillaries (R5: 9.2 +/- 0.8; P < 0.05) and venules (R5: 4.4 +/- 0.5; P < 0.05). When leukocyte margination in coronary venules was examined as a function of venular shear rate, a significant correlation (r = 0.99, P < 0.05) was found. These results suggest that, after ischemia, a reduction in reflow enhances leukocyte trapping in capillaries and that leukocyte adhesion in venules is inversely related to shear rate. Enhanced leukocyte accumulation may in turn increase the leukocyte contribution to early reperfusion injury in the heart.
在心肌缺血后的早期再灌注过程中，心脏中白细胞积聚的机制尚不清楚。我们研究了再灌注期间减少冠状动脉血流量对冠状动脉毛细血管和毛细血管后微静脉中白细胞积聚的影响。将离体大鼠心脏灌注30分钟，然后在37℃下进行30分钟的无血流缺血。再灌注5、20和35分钟后，使用活体显微镜直接观察冠状动脉毛细血管和微静脉中荧光标记白细胞的沉积情况。再灌注5分钟（R5）后测量微静脉中的血细胞速度，并计算剪切率（s-1）。研究了四组：非缺血对照组（NIC）心脏以及缺血后以全流量（I/R100）、全流量的50%和10%（分别为I/R50和I/R10）进行再灌注的心脏。在I/R100组心脏中，与NIC组相比，毛细血管中的白细胞滞留显著增加（R5时：分别为5.7±0.6个白细胞/毛细血管视野和2.0±0.4个白细胞/毛细血管视野；P<0.05）。然而，与NIC组相比，微静脉中白细胞黏附的增加在统计学上并不显著（R5时：分别为3.2±0.4个白细胞/100微米微静脉和1.5±0.6个白细胞/100微米微静脉；P<0.2）。在I/R50组心脏中，毛细血管中的白细胞积聚进一步增加，但微静脉中没有。然而，在I/R10组心脏中，毛细血管（R5时：9.2±0.8；P<0.05）和微静脉（R5时：4.4±0.5；P<0.05）中的白细胞积聚均有统计学显著增加。当将冠状动脉微静脉中的白细胞靠边现象作为微静脉剪切率的函数进行研究时，发现存在显著相关性（r = 0.99，P<0.05）。这些结果表明，缺血后再灌注血流减少会增强白细胞在毛细血管中的滞留，并且微静脉中白细胞的黏附与剪切率呈负相关。白细胞积聚增强可能反过来增加白细胞对心脏早期再灌注损伤的作用。
