NEUTROPHIL DEPLETION LIMITED TO REPERFUSION REDUCES MYOCARDIAL INFARCT SIZE AFTER 90 MINUTES OF ISCHEMIA - EVIDENCE FOR NEUTROPHIL-MEDIATED REPERFUSION INJURY
NEUTROPHIL DEPLETION LIMITED TO REPERFUSION REDUCES MYOCARDIAL INFARCT SIZE AFTER 90 MINUTES OF ISCHEMIA - EVIDENCE FOR NEUTROPHIL-MEDIATED REPERFUSION INJURY
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DOI：
10.1161/01.cir.80.6.1816
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发表时间：
1989-12-01
期刊：
影响因子：
37.8
通讯作者：
BECKER, LC
中科院分区：
文献类型：
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作者：
LITT, MR;JEREMY, RW;BECKER, LC
缺血心肌再灌注可加速损伤心肌细胞的坏死。为了确定中性粒细胞在这一过程中的作用，我们研究了在再灌注过程中中性粒细胞耗竭是否可以改变麻醉犬的梗死面积。将近端回旋冠状动脉闭塞90分钟，然后通过体外回路用全血（n = 11）或用白细胞过滤器去除中性粒细胞的血液（n = 11）再灌注2小时。白细胞过滤器在缺血心肌的血液再灌注中引起几乎全部的中性粒细胞减少症（7 . ±. 7个中性粒细胞/μ l，相比之下为2，551 ±。对照组为317/μ l，平均值±。SEM; p < 0.001。采用氯化三苯基四氮唑（TTC）染色的心肌切片面积法测量心肌面积，并通过电镜检查验证TTC识别坏死心肌的准确性。缺血危险区的大小与对照组相同（41.6 ± 0.00000）。1.0%）和血小板减少症（41.8 . ±. 2.1%）组。在对照组中，流向危险区域的侧支血流是相同的（0.15 ± 0.15）。0.03 ml/min/g）和阿糖胞苷（0.13 ± 0.001）。0.03 ml/min/g）组。在侧支血流量小于0.2 ml/min/g的狗中，血小板减少组的梗死面积减小（27.7 ± 0.00000）。6.7%的风险区域，n = 8），与对照犬（52.5 ±. 5.7%; n = 7; p = 0.02）。多元线性回归描述了对照组中梗死面积、危险区面积和侧支血流之间的关系，并且相同的回归关系用于预测血小板减少组的梗死面积。血小板减少组（n = 11）的平均预测梗死面积为16.8 ± 0.05。3.4%的左心室，而平均观察到的梗死面积为9.6 ±。3.1%（p < 0.01）。无复流区的范围（没有硫黄素-S-荧光）在血小板减少症组中也小于对照组（2.2 ± 0.05）。0.8% vs. 8.1 .+-.上升区的2.7%，p < 0.05）。局限于再灌注期的中性粒细胞减少与缺血90分钟后梗死范围和无复流区的显著减少相关。这些发现支持了这一假设，即再灌注坏死发生后，长期心肌缺血，并表明，中性粒细胞是这种再灌注损伤的重要介质。
Reperfusion of ischemic myocardium may accelerate necrosis of injured myocytes. To determine the role of neutrophil leukocytes in this process, we examined whether neutrophil depletion during reperfusion could modify infarct size in anesthetized dogs. The proximal circumflex coronary artery was occluded for 90 minutes and then reperfused for 2 hours via an extracorporeal circuit with either whole blood (n = 11) or with blood depleted of neutrophils by leukocyte filters (n = 11). The leukocyte filters caused near-total neutropenia in blood reperfusing the ischemic myocardium (7 .+-. 7 neutrophils/.mu.l compared with 2,551 .+-. 317/.mu.l in controls, mean .+-. SEM; p < 0.001. Infarct size was measured by planimetry of myocardial slices stained with triphenyltetrazolium chloride (TTC), and the accuracy of TTC for identifying necrotic myocardium was verified by electron microscopy. The size of the ischemic risk region was the same in the control (41.6 .+-. 1.0%) and neutropenic (41.8 .+-. 2.1%) groups. Collateral blood flow to the risk region was the same in control (0.15 .+-. 0.03 ml/min/g) and neutropenic (0.13 .+-. 0.03 ml/min/g) groups. Among dogs with collateral flow less than 0.2 ml/min/g, infarct size was reduced in the neutropenic group (27.7 .+-. 6.7% of risk region, n = 8), compared with control dogs (52.5 .+-. 5.7%; n = 7; p = 0.02). Multiple linear regression described the relation between infarct size, risk region size, and collateral flow in the control group, and the same regression relation was used to predict infarct size for the neutropenic group. Mean predicted infarct size in the neutropenic group (n = 11) was 16.8 .+-. 3.4% of left ventricle, whereas mean observed infarct size was 9.6 .+-. 3.1% (p < 0.01). The extent of the no-reflow zone (absence of thioflavin-S-fluorescence) was also less in the neutropenic than the control group (2.2 .+-. 0.8% vs. 8.1 .+-. 2.7% of the rise region, p < 0.05). Neutropenia limited to the reperfusion period is associated with significant reductions in the extent of the infarct and no-reflow zones after 90 minutes of ischemia. These findings support the hypothesis that reperfusion necrosis occurs after prolonged myocardial ischemia and indicate that neutrophil leukocytes are important mediators of such reperfusion injury.