Annich G M, Meinhardt J P, Mowery K A, Ashton B A, Merz S I, Hirschl R B, Meyerhoff M E, Bartlett R H
Division of Pediatric Critical Care Medicine, University of Michigan, Ann Arbor 48109-0243, USA.
Crit Care Med. 2000 Apr;28(4):915-20. doi: 10.1097/00003246-200004000-00001.
To determine whether the use of nitric oxide (NO)-releasing polymers coated onto the inner surface of extracorporeal circuits can reduce platelet consumption and activation in the absence of systemic heparinization using a rabbit model of venovenous extracorporeal circulation.
Prospective, controlled trial.
Research laboratory at an academic medical institution.
New Zealand White Rabbits.
Anesthetized, tracheotomized, and ventilated New Zealand White rabbits were injected with freshly prepared, 111In(oxine)3 labeled single donor platelets through the external jugular vein. After baseline measurements, these animals were placed on venovenous extracorporeal circulation through a 1-m control circuit or NO test circuit for 4 hrs at a blood flow rate of 109-118 mL/min via roller pump. Four groups were studied: systemically heparinized control circuits, systemically heparinized NO test circuits, nonheparinized control circuits, and nonheparinized NO test circuits. Platelet counts, fibrinogen levels, and plasma free indium levels were measured hourly. Circuits were rinsed and retained for gamma counting after the 4-hr run or when the circuit clotted. Four animals, one from each group, did not receive radiolabeled platelets so that the circuits could be preserved for scanning electron microscopic examination after the 4-hr study.
Platelet consumption was significantly reduced in both the heparinized and nonheparinized NO test groups when compared with the controls (p < .0001 and p < .0004, respectively). Platelet adhesion to the extracorporeal circuits was significantly reduced in the nonheparinized test circuits when compared with the controls (p < .05). Scanning electron microscopic examination of the circuits revealed that in the absence of heparin and in the presence of a NO-releasing surface, platelets retained their spherical nonactivated shape.
The incorporation of NO into the surface of extracorporeal circuits reduces platelet consumption and eliminates the need for systemic heparinization in a rabbit model of extracorporeal circulation.
使用兔静脉-静脉体外循环模型,确定涂覆在体外循环回路内表面的释放一氧化氮(NO)的聚合物在无全身肝素化的情况下是否能减少血小板消耗和活化。
前瞻性对照试验。
一所学术性医疗机构的研究实验室。
新西兰白兔。
对麻醉、气管切开并通气的新西兰白兔经颈外静脉注射新鲜制备的、用111In(氧嗪酸盐)3标记的单供体血小板。在进行基线测量后,将这些动物通过1米长的对照回路或NO测试回路以109 - 118毫升/分钟的血流速度经滚压泵进行静脉-静脉体外循环4小时。研究了四组:全身肝素化对照回路、全身肝素化NO测试回路、非肝素化对照回路和非肝素化NO测试回路。每小时测量血小板计数、纤维蛋白原水平和血浆游离铟水平。在运行4小时后或回路凝血时,冲洗回路并保留用于γ计数。每组有4只动物未接受放射性标记血小板,以便在4小时研究后将回路保存用于扫描电子显微镜检查。
与对照组相比,肝素化和非肝素化NO测试组的血小板消耗均显著降低(分别为p < .0001和p < .0004)。与对照组相比,非肝素化测试回路中血小板与体外循环回路的黏附显著降低(p < .05)。对回路的扫描电子显微镜检查显示,在无肝素且存在释放NO表面的情况下,血小板保持其球形非活化形状。
在兔体外循环模型中,将NO整合到体外循环回路表面可减少血小板消耗并消除全身肝素化的需求。