Chapelier A, Reignier J, Mazmanian M, Detruit H, Dartevelle P, Parquin F, Cerrina J, Le Roy Ladurie F, Hervé P
Laboratoire de Chirurgie Expérimentale, Hôpital Marie Lannelongue, Université Paris Sud, France.
J Cardiovasc Pharmacol. 1995;25 Suppl 2:S130-3.
Pentoxifylline (PTX) attenuates neutrophil-mediated lung injury in several models of acute lung inflammation. Because pulmonary neutrophil sequestration is the main determinant of ischemia-reperfusion (IR) injury in lung transplantation, we sought to determine whether or not PTX prevented IR injury in isolated perfused rat and rabbit lungs submitted to IR, and in pigs after left lung allotransplantation. In rat lungs after IR, the coefficient of lung endothelial permeability (Kfc) increased by 112 +/- 12% in controls and by 27 +/- 8% (p < 0.001) in PTX-treated lungs. After IR, lung myeloperoxidase and blood neutrophil count decrease were lower with PTX than in controls, and the changes in Kfc were correlated with the percentage decrease in blood neutrophils during reperfusion. In rabbit lungs, endothelium-dependent relaxation in isolated pulmonary arterial rings was decreased in the control group and normal in the PTX group. In pigs ventilated with pure oxygen, the PaO2 was greater in the PTX group than in the control group (423 +/- 49 vs. 265 +/- 43 mm Hg; p < 0.05), whereas the total pulmonary vascular resistance was lower (15 +/- 1 vs. 30 +/- 9 mm Hg/L/min; p < 0.02). After reperfusion, the decrease in circulating leukocyte count fell by 35 +/- 3% in the control group and remained unchanged in the PTX group, and the leukocyte count per microscopic field in the transplanted lung was lower in the PTX group than in the control group (p < 0.02). In conclusion, PTX prevented IR lung endothelium injury and improved post-IR lung function by decreasing neutrophil lung sequestration, and this agent might be useful in clinical lung transplantation.
己酮可可碱（PTX）在几种急性肺炎症模型中可减轻中性粒细胞介导的肺损伤。由于肺中性粒细胞隔离是肺移植中缺血再灌注（IR）损伤的主要决定因素，我们试图确定PTX是否能预防离体灌注的大鼠和兔肺在经历IR时以及猪左肺同种异体移植后的IR损伤。在IR后的大鼠肺中，对照组肺内皮通透性系数（Kfc）增加了112±12%，而PTX处理组增加了27±8%（p<0.001）。IR后，PTX组肺髓过氧化物酶和血中性粒细胞计数的降低幅度低于对照组，且Kfc的变化与再灌注期间血中性粒细胞的降低百分比相关。在兔肺中，对照组离体肺动脉环的内皮依赖性舒张降低，而PTX组正常。在纯氧通气的猪中，PTX组的动脉血氧分压高于对照组（423±49 vs. 265±43 mmHg；p<0.05），而总肺血管阻力较低（15±1 vs. 30±9 mmHg/L/min；p<0.02）。再灌注后，对照组循环白细胞计数下降了35±3%，而PTX组保持不变，且PTX组移植肺每高倍视野的白细胞计数低于对照组（p<0.02）。总之，PTX通过减少中性粒细胞在肺中的隔离预防了IR肺内皮损伤并改善了IR后的肺功能，该药物可能对临床肺移植有用。
