EVALUATION OF THE PLATELET PROTECTING EFFECTS OF NITRIC OXIDE (NO) AND APROTININ DURING CARDIOPULMONARY BYPASS

心肺转流过程中一氧化氮（NO）和抑肽酶的血小板保护作用评价

• 批准号: 08671771
• 负责人: MORITA Shigeho
• 金额: $ 1.02万
• 依托单位: TEIKYO UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671771/
• 关键词: cardiopulmonary bypass; nitric oxide; coronary artery bypass grafting; platelet function; postoperative bleeding; flow cytometry; aprotinin; monoclonal antibody; 血小板; NO; フローサイトメトリー法

We have undertaken these studies to examine whether NO gas can reduce platelet activation and blood loss in patients who had elective coronary artery bypass grafting (CABG) with CPB.We also compared the effects of NO gas to aprotinin. The data from remaining 20 patients were subsequently analyzed.CPB was performed at a minimal temperature of 28ﾟC with a nonpulsatile flow of 2.4 L/min/kg. Chest tube draignage was recorded hourly until removal of drains. In patietnts who received aprotinin, 500,000 KIU of aprotinin was slowly given after the induction of anesthesia and before the start of CPB,and another 500,000 KIU aprotinin was added to pump priming solution. NO gas was mixed into the sweep gas flow of the membrane oxygenator, with a specially made flow meter. Concentration of oxygen, NO,NO2 were measured immediately before and after the oxygenator, and NO gas flow was adjusted so that 100 ppm NO gas was mixed into the oxygenator sweep gas. Platelet activation is quantified based on th … More e increased surface expression of P-selectin (CD62). The decreased surface expression of GPlb (CD42b) was also regarded as alteration of platelet function caused by CPB,and quantified. Anslysis of list mode data files was performed using CELLQuest software (Beckton Dickinson Immunocytometry Systems).In control and NO treated patients, activated platelets, indicated by increased events positive for CD62PE,significantly increased during and after CPB.In aprotinin-treated patients, platelet activation was modestly attenuated during CPB.There was a tendency that blood loss during the first 24 hrs after operation was modestly decreased by aprotinin treatment, but statistical significance was not achieved at this point. No difference was found between, control and the NO-treated group in 24 hr blood loss.Since currently we do not have enough number of patients in our study, we cannot make any conclusion at this point. However, preliminary results from out study showed that giving NO at 100 ppm to the membrane oxygenator sweep gas does not reduce platelet activation due to the synthetic surfaces of CPB.The amount of blood loss during the first 24 hrs after the operation was also not altered by NO gas infusion. On the other hand, low dose aprotinin employed in our study attenuated platelet activation as previously reported with higher doses of aprotinin. There was a tendency that aprotinin decreased postoperative blood loss in the first 24 hours, but statistical significance was not achieved at this point. We will increase number of patients and also try to examine the effects of NO gas plus aprotinin on platelet activation during CPB. Less

我们已经进行了这些研究，以检查是否NO气体可以减少血小板活化和失血的病人谁选择性冠状动脉旁路移植术（CABG）与CPB。我们还比较了NO气体抑肽酶的影响。对其余20例患者的数据进行分析，CPB在最低温度28 ℃，非脉动流量2.4 L/min/kg下进行。每小时记录一次胸管引流，直至取出引流管。在接受抑肽酶的患者中，在麻醉诱导后和CPB开始前缓慢给予50万KIU抑肽酶，并在泵预充液中加入另外50万KIU抑肽酶。用特制的流量计将NO气体混合到膜式氧合器的吹扫气流中。在氧合器之前和之后立即测量氧、NO、NO2的浓度，并且调节NO气流，使得100 ppm NO气体混合到氧合器吹扫气体中。血小板活化是根据血小板活化的程度来量化的。 ...更多信息 e增加P-选择素（CD 62）的表面表达。GP 1b（CD 42 b）表面表达的降低也被认为是CPB引起的血小板功能的改变，并进行定量。使用CELLQuest软件对列表模式数据文件进行分析（Beckton Dickinson Immunocytometry Systems）。在对照和NO治疗的患者中，活化的血小板（由CD 62 PE阳性事件的增加指示）在CPB期间和之后显著增加。体外循环期间血小板活化适度减弱。术后24小时内失血量有适度减少的趋势，抑肽酶治疗，但在这一点上没有达到统计学意义。在24小时失血量方面，对照组和NO治疗组之间没有发现任何差异。由于目前我们的研究中没有足够的患者数量，我们不能在这一点上做出任何结论。然而，本研究的初步结果表明，向膜式氧合器吹扫气体中加入100 ppm的NO不会降低CPB合成表面引起的血小板活化。NO气体输注也不会改变术后前24小时的失血量。另一方面，在我们的研究中使用的低剂量抑肽酶减弱了血小板活化，如先前报道的高剂量抑肽酶。有一种趋势，抑肽酶减少术后失血量在第一个24小时，但在这一点上没有达到统计学意义。我们将增加患者数量，并尝试检查NO气体加抑肽酶对CPB期间血小板活化的影响。少