Kermarrec N, Zunic P, Beloucif S, Benessiano J, Drouet L, Payen D
Department of Anesthesiology and Critical Care Medicine, and Department of Hematology, Unité d'Enseignement et de Recherche de Médecine Lariboisière-Saint-Louis, Université Paris VII, Paris, France.
Am J Respir Crit Care Med. 1998 Sep;158(3):833-9. doi: 10.1164/ajrccm.158.3.9709097.
As inhaled nitric oxide (iNO) may differently increase bleeding time (BT) and inhibit platelet aggregation in normal and lung-injured patients or experimental models, we studied the effects of iNO on hemostasis in presence and absence of an endotoxic lung injury in the rat. Eight hours after intratracheal administration of endotoxin (lipopolysaccharide [LPS]) or its solvent (phosphate-buffered solution [PBS]), four groups of rats were randomized according to the presence or absence of 15 ppm iNO added for an additional 10 h. We measured BT, ex vivo platelet aggregation, plasma fibrinogen, euglobulin clot lysis time (ECLT), and platelet and aortic cyclic guanosine 5'-monophosphate (cGMP) contents. Acute lung inflammation did not influence BT, but increased platelet aggregability, fibrinogen levels, and platelet and aortic cGMP. In control and endotoxic rats, iNO increased BT, reduced platelet aggregability, and increased platelet cGMP. iNO increased aortic cGMP only in healthy rats. ECLT was increased by LPS and unchanged with iNO. These results suggest that the extrapulmonary "systemic" effects induced by iNO on hemostasis were not strictly similar in healthy and LPS rats, inflammation inducing proper changes in coagulation parameters. However, iNO attenuated the procoagulant activity induced by acute lung inflammation, suggesting a potentially beneficial effect of this therapy.
由于吸入一氧化氮（iNO）可能会使正常患者和肺损伤患者或实验模型的出血时间（BT）产生不同程度的增加，并抑制血小板聚集，因此我们研究了在大鼠存在和不存在内毒素性肺损伤的情况下，iNO对止血的影响。在气管内给予内毒素（脂多糖[LPS]）或其溶剂（磷酸盐缓冲溶液[PBS]）8小时后，根据是否添加15 ppm iNO再持续10小时，将四组大鼠随机分组。我们测量了BT、体外血小板聚集、血浆纤维蛋白原、优球蛋白凝块溶解时间（ECLT）以及血小板和主动脉环磷酸鸟苷（cGMP）含量。急性肺部炎症并未影响BT，但增加了血小板聚集性、纤维蛋白原水平以及血小板和主动脉cGMP。在对照大鼠和内毒素血症大鼠中，iNO增加了BT，降低了血小板聚集性，并增加了血小板cGMP。iNO仅在健康大鼠中增加了主动脉cGMP。LPS使ECLT增加，而iNO对其无影响。这些结果表明，iNO对止血产生的肺外“全身”效应在健康大鼠和LPS大鼠中并不严格相似，炎症会引起凝血参数的适当变化。然而，iNO减弱了急性肺部炎症诱导的促凝活性，表明该疗法可能具有有益作用。
