Gillespie M N, Kojima S, Owasoyo J O, Tai H H, Jay M
J Pharmacol Exp Ther. 1987 Jun;241(3):812-6.
Isolated rabbit hearts were perfused with salt solution containing autologous 111In-labeled neutrophils to determine whether 1) hypoxia provoked myocardial neutrophil sequestration, 2) neutrophil accumulation could be suppressed by inhibition of lipoxygenase and 3) hypoxic myocardium generated radioimmunoassayable leukotriene B4 (LTB4). Whereas accumulation of 111In-labeled neutrophils by normoxic hearts was minimal, induction of acute myocardial hypoxia by perfusion with hypoxic medium caused a rapid uptake of 111In-labeled neutrophils. Sequestered neutrophils were not released during a subsequent 20-min normoxic perfusion period. Hypoxia-induced neutrophil uptake was prevented by nordihydroguaiaretic acid (NDGA) or diethylcarbamazine (DEC), two structurally different inhibitors of lipoxygenase. Although no radioimmunoassayable LTB4 could be detected in neutrophil-free perfusate from normoxic or hypoxic preparations, hypoxia caused an approximate 2-fold increase in myocardial tissue levels of LTB4. Tissue levels of LTB4 reverted to control values after 20 min of normoxic perfusion. Infusion of exogenous LTB4 also provoked myocardial neutrophil uptake. Viewed collectively, these observations suggest that in isolated buffer-perfused rabbit hearts hypoxia induces LTB4 release from resident myocardial cells, which promotes avid neutrophil sequestration.
用含有自体铟 - 111标记中性粒细胞的盐溶液灌注离体兔心，以确定：1）缺氧是否会引发心肌中性粒细胞滞留；2）抑制脂氧合酶是否能抑制中性粒细胞聚集；3）缺氧心肌是否会产生可通过放射免疫测定的白三烯B4（LTB4）。正常氧合的心脏对铟 - 111标记中性粒细胞的摄取极少，而用缺氧培养基灌注诱导急性心肌缺氧会导致铟 - 111标记中性粒细胞迅速摄取。在随后20分钟的正常氧合灌注期内，滞留的中性粒细胞不会释放。去甲二氢愈创木酸（NDGA）或二乙氨基甲嗪（DEC）这两种结构不同的脂氧合酶抑制剂可阻止缺氧诱导的中性粒细胞摄取。尽管在正常氧合或缺氧制剂的无中性粒细胞灌注液中未检测到可通过放射免疫测定的LTB4，但缺氧使心肌组织中LTB4水平增加了约2倍。正常氧合灌注20分钟后，LTB4的组织水平恢复到对照值。输注外源性LTB4也会引发心肌中性粒细胞摄取。总体来看，这些观察结果表明，在离体缓冲液灌注的兔心中，缺氧诱导驻留心肌细胞释放LTB4，进而促进中性粒细胞的强烈滞留。
