Salari H, Walker M J
Department of Medicine, University of British Columbia, Vancouver, Canada.
Circ Shock. 1989 Mar;27(3):263-72.
This study was designed to evaluate the role of macrophages in cardiac dysfunction associated with endotoxemia or septic shock. Rat peritoneal macrophages were cultured on glass bead-carrier and placed in the perfusate stream of an isolated rat heart perfused according to the Langendorff technique. The heart was thus perfused with a Krebs solution exposed to macrophages stimulated with endotoxin. After 10-15 min of exposure, the macrophages released substance(s) that decreased left ventricular pressure (VP) 50-80% and coronary flow (CF) without significantly affecting heart rate or the ECG. In a separate study, macrophages were incubated with endotoxin and the incubate injected into the heart; a 20-30% reduction in VP and CF was observed. However, when macrophages were further stimulated with opsonized zymosan, 60-80% reductions in VP and CF were observed. Treatment with prostaglandin antagonists, leukotriene inhibitors, or trypsin did not significantly modify the activity of the material released from macrophages. Free radical scavengers (catalase and superoxide dismutase) reduced the activity of macrophage derived product by 15-20%. However, platelet-activating factor (PAF) antagonist prevented the action of macrophage mediators on the heart by approximately 58%. Heat inactivation destroyed activity released from the macrophages almost entirely. These findings may contribute to a better understanding of endotoxemia and endotoxin shock mechanisms.
本研究旨在评估巨噬细胞在与内毒素血症或脓毒性休克相关的心脏功能障碍中的作用。将大鼠腹腔巨噬细胞培养在玻璃珠载体上，并置于按照Langendorff技术灌注的离体大鼠心脏的灌注液流中。心脏由此用暴露于内毒素刺激的巨噬细胞的 Krebs 溶液灌注。暴露10 - 15分钟后，巨噬细胞释放出某些物质，这些物质使左心室压力（VP）降低50 - 80%，冠状动脉血流量（CF）降低，而对心率或心电图无明显影响。在另一项研究中，将巨噬细胞与内毒素一起孵育，然后将孵育物注入心脏；观察到VP和CF降低了20 - 30%。然而，当用调理的酵母聚糖进一步刺激巨噬细胞时，观察到VP和CF降低了60 - 80%。用前列腺素拮抗剂、白三烯抑制剂或胰蛋白酶处理并未显著改变巨噬细胞释放物质的活性。自由基清除剂（过氧化氢酶和超氧化物歧化酶）使巨噬细胞衍生产物的活性降低了15 - 20%。然而，血小板活化因子（PAF）拮抗剂可使巨噬细胞介质对心脏的作用降低约58%。热灭活几乎完全破坏了巨噬细胞释放的活性。这些发现可能有助于更好地理解内毒素血症和内毒素休克的机制。
