Shin Y K, Campbell B, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Methods Find Exp Clin Pharmacol. 1998 Jul-Aug;20(6):463-71. doi: 10.1358/mf.1998.20.6.485709.
Infiltrating polymorphonuclear leukocytes (PMNs) have been implicated as key mediators of ischemia/reperfusion injury of the heart. These toxic effects are due to PMN and endothelial cell interactions. This microvascular dysfunction results in an impairment of the coronary circulation which enhances myocardial damage. The effect of defibrotide was examined in a neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of defibrotide (200 micrograms/kg) to I/R hearts in the presence of PMNs preserved coronary flow and protected against cardiac contractile dysfunction (p < 0.001) in comparison to those I/R hearts perfused with PMNs but receiving only vehicle. Defibrotide also significantly decreased PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity (p < 0.001). Defibrotide exerted a significant cardioprotection in PMN mediated I/R injury of rat heart. The mechanism appears to be related to inhibition of PMN-endothelium interaction and eventual PMN infiltration into the ischemic myocardium.
浸润的多形核白细胞（PMN）被认为是心脏缺血/再灌注损伤的关键介质。这些毒性作用归因于PMN与内皮细胞的相互作用。这种微血管功能障碍导致冠状动脉循环受损，进而加重心肌损伤。在中性粒细胞依赖性离体灌注大鼠心脏缺血（I）（20分钟）和再灌注（R）（45分钟）模型中研究了去纤苷的作用。与仅接受赋形剂灌注的PMN的I/R心脏相比，在存在PMN的情况下，给I/R心脏施用去纤苷（200微克/千克）可维持冠状动脉血流，并防止心脏收缩功能障碍（p<0.001）。去纤苷还显著降低了缺血心肌中PMN的积聚，髓过氧化物酶活性的降低证明了这一点（p<0.001）。去纤苷对大鼠心脏PMN介导的I/R损伤具有显著的心脏保护作用。其机制似乎与抑制PMN-内皮细胞相互作用以及最终PMN浸润到缺血心肌有关。
