心脏停跳复苏后全脑浅低温对脑组织前列环素和血栓素A_2含量的影响

观察犬心脏停跳复跳后全脑浅低温（３４℃）对脑组织前列环素和血栓素 Ａ2 含量的影响。结 果表明，脑缺血再灌注后常规治疗４小时，６－ｋｅｔｏ－ＰＧＦ１ａ水平无明显变化，ＴＸＢ２含量明显上升（Ｐ＜ ０． ０１），ＴＸＢ２／６－ｋｔｅｏ－ＰＧＦ１ａ（Ｔ／Ｋ）比值明显升高（Ｐ＜０．０１）；浅低温治疗组与缺血再灌常规治疗组比较 ６－ｋｅｔｏ－ＰＧＦ１ａ水平仍无明显变化，而ＴＸＢ２含量下降（Ｐ＜０．０５），Ｔ／Ｋ比值降低（Ｐ＜０．０５）。提示全脑浅 低温能抑制脑缺血再灌后花生四烯酸环氧酶途径代谢，调整脑内前列环素与血栓素Ａ２的平衡，有利于 脑复苏。     

心脏停跳复苏后全脑浅低温对脑组织前列环素和血栓素A2含量…

观察犬心脏停跳复跳后全脑浅低温对脑组织前列环素和血栓素Ａ２含量的影响。结果表明，脑缺血再灌注后常规治疗４小时，６－ｋｅｔｏ－ＰＧＦ１ａ水平无明显变化。ＴＸＢ２含量明显上升，ＴＸＢ２／６－ｋｔｅｏ－ＰＧＦ１ａ（Ｔ／Ｋ）比值明显升高；浅低温治疗组与缺血再灌常规治疗组比较６－ｋｅｔｏ－ＰＧＦ１ａ水平仍无明显变化，而ＴＸＢ２含量下降（Ｐ＜０．０５），Ｔ／Ｋ比值降低（Ｐ＜０．０５）。提示全脑浅低温能抑制脑缺     

阿魏酸钠对犬心脏停跳复苏后脑组织TXB_2、6-keto-PGF_(1a)及MDA含量的影响

研究了阿魏酸钠对犬心脏停跳１０分钟复苏后４小时脑组织中血栓素Ｂ２（ＴＸＢ２）、６－酮－前列腺素Ｆ１ａ（６－ｋｅｔｏ－ＰＧＦ１ａ）及丙二醛（ＭＤＡ）含量的影响。１７只犬随机分为非缺血对照组（Ａ组）、缺血再灌注常规治疗组（Ｂ组）及缺血再灌注阿魏酸钠治疗组（Ｃ组）。结果发现，Ｂ组ＴＸＢ２、ＭＤＡ含量及ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１ａ比值均较 Ａ组明显升高（Ｐ＜０． ０１）。 Ｃ组 ＴＸＢ２、ＭＤＡ含量及 ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１ａ比值升高幅度均较Ｂ组明显低（Ｐ＜０．０１）。表明阿魏酸钠可明显抑制犬心脏停跳复苏后脑组织花生四烯酸代谢及脂质过氧化反应。     

复方丹参对体外循环患者血清内皮素和血栓素水平的影响

目的：观察复方丹参（ＳＭＣ）对体外循环（ＣＰＢ）下心肌缺血再灌注损伤血清内皮素（ＥＴ），血栓素（ＴＸＢ２）和６－ｋｅｔｏ－ＰＧＦ１α（ＰＧＦ１α）变化的。方法：２０例先天性心脏病室缺（ＶＳＤ）房缺（ＡＳＤ）修补患者随机分为对照组（组Ｉ，１０例）及复方丹参组（组Ⅱ，１０例）组Ⅱ于切皮前３０分与复温时至心脏复跳前，分别静脉滴主ＳＭＣ２００ｍｇ／ｋｇ，组Ｉ在同一时间给阳等量平衡盐液，两组于术前（Ｔ０），     

青心酮对大鼠被动吸烟胎儿宫内生长迟缓的疗效观察

选择１５０只健康ＳＤ妊娠大鼠，均于妊娠Ｄ４～Ｄ２０天仿Ｙｏｕｎｏｓｚａｉ法制备胎儿宫内生长迟缓模型。按治疗药物随机分为６组。观察复方氨基酸和青心酮的疗效。结果：（１）模型组的胎仔平均体重、身长和肝重量都明显低于对照组（Ｐ＜０．０１）。胎仔发育参数各用药组与模型组比较有显著差异（Ｐ＜０．０１）。各用药组之间无明显差异（Ｐ＞０．０５）。（２）孕鼠血红蛋白（Ｈｂ）、红细胞压积（Ｈｔ）水平在模型组明显高于其它５组（Ｐ＜０．０１），各用药组之间无明显差异（Ｐ＞０．０５）。各组胎仔平均体重与母血Ｈｂ、Ｈｔ呈负相关。（３）孕鼠血浆Ｅ３，６－ｋｅｔｏ－ＰＧＦ１ａ水平模型组明显低于其它５组（Ｐ＜０．０１），而ＴＸＢ２无明显改变，ＴＸＢ２／６－ｋｅｔｏ－ｐＧＦ１ａ比值模型组明显高于其它５组（Ｐ＜０．０１）。结果说明青心酮治疗胎儿宫内生长迟缓的药效与其调整ＴＸＡ２－ＰＧＩ２失衡有关。     

体外震波碎石前后血浆和尿液PGI2与TXA2的变化及其临床意义

应用放射免疫技术，对１４例非梗阻性单纯肾结石患者ＳＥＷＬ前后血浆和尿液中ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１ａ水平进行了动态检测。结果显示，血浆ＴＸＢ２在ＥＳＷＬ后第一天明显升高（Ｐ＜０．００１），而６－ｋｅｔｏ－ＰＧＦ１α无显著意义的改变（Ｐ＞０．０５），两者的比值也随ＴＸＢ２而升高（Ｐ＜Ｏ．００１），第三天时都降至基础水平；尿液中上述指标也出现类似变化。我们认为，ＥＳＷＬ后早期肾脏内ＴＸＡ２合成与释放增加，ＴＸＡ２与ＰＧＩ２平衡失调，有可能参与了肾损害的病理生理过程。     

体外循环时小剂量抑肽酶对纤溶系统和血小板的影响

心脏直视手术体外循环时应用小剂量抑肽酶，观察其对纤溶系统和血小板的影响。３０例随机分为对照组和抑肽酶用药组。用药组仅一次在预充液中加入小剂量抑肽酶２×１０６ＫＩＵ。分别于转流前、转流３０分钟、转流结束时及转流停止后２小时测定ＰＬＧ、ＦＤＰ、ＰＫ、ＴＸＢ２、ｔ－ＰＡ、６－ｋｅｔｏ－ＰＧＦ１α，ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α浓度。术后２４小时纵隔心包引流量用药组较对照组减少出血４１．７％，Ｐ＜０．０１。电镜观察用药组血小板改变不明显；对照组呈现破碎、脱颗粒、微管扩张、聚集。作者认为小剂量抑肽酶能有效地抑制高纤溶活性，可保护血小板功能，减少术后出血。     

气管插管应激时血浆血栓素A2和前列环素含量变化

为比较气管插管应激时血浆血栓素Ａ２（以ＴｘＢ２表示）和前列环素（以６－ｋｅｔｏ－ＰＧＦ１ａ表示）的变化，２２例患者随机分为芬太尼组和对照组，两组患者均给予硫喷妥钠４ｍｇ／ｋｇ和琥珀胆碱１。５ｍｇ／ｋｇ诱导后插管，结果显示诱导后５分内，对照组ＳＢＰ、ＤＢＰ、ＭＡＰ、ＨＲ、ＰＡＷＰ、ＴＰＲ及血浆ＴＸＢ２含量较芬太尼组明显升高（Ｐ＜０。０５），对照组ＴＸＢ２的升高与ＭＡＰ及ＴＰＲ的升高呈高度正相关系，对     

移植肾急性排斥时血栓素A2、前列环素代谢改变及其对肾小球滤过率的影响

用放射免疫法检测２１例移植肾急性排斥时，肾移植患者尿液以及血浆血栓素Ｂ２（ＴＸＢ２）和６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）浓度，并检测４例不可逆急性排斥和７例慢性排斥移植肾切除后肾组织ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α含量。发现急性排斥出现时，尿中ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α含量均明显升高，ＴＸＢ２增多出现较早；血浆ＴＸＢ２浓度也显著增加，６－ｋｅｔｏ－ＰＧＦ１α浓度下降。尿液和血浆中ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值增大。正常肾组织标本中，肾髓质ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α含量为皮质的４～５倍，皮髓质中ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值水平相同。不可逆急性排斥肾组织中，肾皮质ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值明显高于髓质。急性排斥时，尿液中ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α比值变化与肾皮质平行。分析表明，急性排斥时，尿液ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值增大和移植肾肾小球滤过率负相关。     

川芎嗪改善大鼠胰腺保存的机理

通过测定保存不同时间后未移植胰腺组织内６－酮－前列腺素Ｆ１α及血栓素Ｂ２含量，对川芎嗪改善胰腺保存效果的作用机制作出初步探讨。６－ｋｅｔｏ－ＰＧＦ１α及ＴＸＢ２测定结果显示：加川芎嗪对６－ｋｅｔｏ－ＰＧＦ１α无明显影响，对ＴＸＢ２则能显著性降低，６ｋｅｔｏ－ＰＧＦ１α；ＴＸＢ２的比值在加川芎嗪组最大，认为川芎嗪主要通过抑制ＴＸＡ２合成，升高ＰＧＩ２：ＴＸＡ２的比２值，发挥ＰＧＩ２的保护作用，抑制Ｔ     

Arachidonic acid metabolism and effectiveness of aprotinin treatment during cardiopulmonary bypass]

Arachidonic acid metabolism was investigated in 30 open heart cases, utilizing nonpulsatile cardiopulmonary bypass (CPB), consisted of 15 untreated cases (Group I) and 15 cases treated with aprotinin mostly given into CPB circuit during CPB (Group II). In group I, arterial blood concentration of thromboxane B2 (TXB2, stable metabolite of thromboxane A2, pg/ml) significantly increased from 45.9 +/- 40.5 preoperatively to 560.2 +/- 381.5 (p less than 0.01) at 30 minutes of CPB (total bypass) and to 830.5 +/- 591.1 (p less than 0.005) at the end of CPB (partial bypass). TXB2 levels in pulmonary artery (PA) and left atrium (LA) did not significantly increase just before, 5 minutes of CPB as compared with preoperative value. At the end of CPB TXB2 levels in PA (625.0 +/- 186.3) and LA (817.0 +/- 320.0) were significantly higher than preoperative value. However there was no significant difference between PA and LA values. Contrarily in group II TXB2 levels were significantly suppressed as compared with the value at each corresponding time in group I. beta-thromboglobulin levels also changed almost parallel to TXB2 levels in both groups. In conclusion, arachidonic acid metabolic disorders could occur in CPB circuit rather than in pulmonary circulation during CPB. Aprotinin administration into CPB circuit suppressed to some extent the platelet activation.     

七氟醚预处理联合后处理对大鼠心肌缺血再灌注时血栓素A2和前列腺素I2的影响

目的 评价七氟醚预处理联合后处理对大鼠心肌缺血再灌注时血栓素A2和前列腺素I2的影响.方法 健康雄性Wistar大鼠50只,体重250～280 g,采用随机数字表法,将大鼠随机分为5组(n=10):假手术组(S组)、缺血再灌注组(I/R组)、七氟醚预处理组(Spr组)、七氟醚后处理组(Spo组)和七氟醚预处理联合七氟醚后处理组(Spr+po组).I/R组、Spr组、Spo组和Spr+po组采用结扎左冠状动脉前降支30 min时进行再灌注的方法制备心肌缺血再灌注模型,S组仅在左冠状动脉前降支下穿线.Spr组进行七氟醚预处理:于缺血前30 min吸入2.5%七氟醚15 min,洗脱15 min;Spo组进行七氟醚后处理:再灌注前1 min开始吸入2.5%七氟醚,持续5 min;Spr+po组进行七氟醚预处理和后处理.再灌注2 h时取动脉血样,测定血MB型磷酸肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cTnI)、血栓素B2(TXB2)、6-酮-前列腺素F1α(6-keto-PGF1α)的水平和血小板最大聚集率,并计算TXB2与6-keto-PGF1α的比值(TXB2/6-keto-PGF1α).取心肌组织,电镜下观察病理学结果,进行线粒体损伤评分,并测定线粒体的比表面和面数密度.结果 与S组比较,I/R组血CK-MB、LDH、cTnI、TXB2、6-keto-PGF1α的水平、TXB2/6-keto-PGF1α血小板最大聚集率及线粒体损伤评分升高,线粒体的比表面和面数密度降低(P<0.05或0.01);与I/R组比较,Spr组和Spo组血CK-MB、LDH、cTnI的水平、TXB2/6-keto-PGF1α和线粒体损伤评分降低,血6-keto-PGF1α浓度、线粒体的比表面和面数密度升高(P<0.05或0.01);与Spr组和Spo组比较,Spr+po组血CK-MB、LDH、cTnI、TXB2的水平、TXB2/6-keto-PGF1α血小板最大聚集率和线粒体损伤评分降低,血6-keto-PGF1α浓度、线粒体的比表面和面数密度升高(P<0.05).Spr+po组心肌损伤程度轻于Spr组和Spo组.结论 与七氟醚预处理或后处理比较,两种方法联合应用可抑制血栓素A2的释放和促进前列腺素I2的释放,从而进一步减轻了大鼠心肌缺血再灌注损伤.

Abstract：

Objective To investigate the effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion (I/R) in rats. Methods Fifty healthy male Wistar rats weighing 250-280 g were randomly divided into 5 groups (n = 10 each) : sham operation group (group S) , I/R group, sevoflurane preconditioning group (group Spr), sevoflurane postconditioning group (group Spo)and combination of sevoflurane preconditioning and postconditioning group (group Spr + po). Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion in anesthetized rats. In group S the anterior descending branch was only exposed but not ligated. Group Spr received 15 min inhalation of 2.5 % sevoflurane and 15 min wash-out 30 min before ischemia. Group Spo received 5 min inhalation of 2.5% sevoflurane 1 min before reperfusion. Arterial blood samples were taken at 2 h of reperfusion for determination of the levels of MB isoenzyme of creatine kinase (CK-MB) , lactate dehydrogenase (LDH) , cardiac troponin I (cTnI), thromboxane B2(TXB2), and 6-keto-prostaglandin (6-keto-PGF1α) and platelet maximum aggregation rate. TXB2/6-keto-PGF1α ratio was calculated. The myocardial tissues were taken for microscopic examination. Mitochondria] injury was assessed by using Flameng score and stereology (Specific surface, δ and Numerical density on area, NA) .Results Compared with group S, the levels of CK-MB, LDH, cTnI, TXE2 and 6-ketoPGF1α, TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly increased, while δ and NA were significantly decreased in group I/R (P < 0.05 or 0.01) . The levels of CK-MB,LDH and cTnI, TXB2/6-keto-PGF1α ratio and Flameng score were significantly lower, and 6-keto-PGF1α level, δand NA were significantly higher in Spr and Spo groups than in group I/R ( P < 0.05 or 0.01) . The levels of CKMB, LDH, cTnI and TXB2 , TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly lower and 6-keto-PGF1α level,δ and NA were significantly higher in group Spr + po than in Spr and Spo groups(P < 0.05). Conclusion Sevoflurane preconditioning-postconditioning can reduce myocardial I/R injury through inhibiting the release of thromboxane A2 and promoting the release of prostaglandin I2 in rats.     

含抑肽酶低温灌注液减轻体外循环肺损伤

目的;研究体外循环期间低温保护液肺动脉灌注对肺脏的保护作用。方法;１２只杂种犬随机均分为２组。主动脉阻断后,对照组右肺动脉灌注４℃乳酸林格液,实验组灌注４℃肺保护液。开放主动脉后和停ＣＰＢ后５,３０,６０,９０分钟;分别取各组肺静脉血标本行生化分析,测定肺功能,并行组织学检查。     

Plasma level and effects of thromboxane A2 and 6-keto-PGF1 alpha in patients with acute obstructive suppurative cholangitis

The changes of the plasma thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, the stable metabolites of TXA2 and PGI2, respectively and their effects on platelet counts, platelet aggregation and hypotension were studied in patients with AOSC. The results showed that the plasma TXB2, 6-keto-PGF1 alpha and 6-keto-PGF1 alpha/TXB2 ratios in these patients were markedly increased, however, the platelet counts markedly decreased and platelet aggregation inhibited significantly. After operation, they recovered to normal gradually. There were negative correlation between TXB2 with platelet count and 6-keto-PGF1 alpha with platelet aggregation, as well as both TXB2 and 6-keto-PGF1 alpha with blood pressure. TXA2 was an important factor which lead to platelet decrement and take part in the pathological course of disseminated intravascular coagulation (DIC) and multiple organ failure (MOF), but PGI2 might play an important role in improving microcirculation and preventing DIC and MOF through the inhibition of platelet aggregation.     

Effects of aprotinin on prostaglandin metabolism and platelet function in open heart surgery.

The effects of the protease inhibitor, aprotinin, on plasma prostaglandin levels and platelet function during and after cardiopulmonary bypass (CPB) were studied in a group of 23 patients which consisted of 11 untreated patients (control group) and 12 aprotinin-treated patients (aprotinin group). Thromboxane B2 (TXB2, a stable metabolite of thromboxane A2) and beta-thromboglobulin levels in the control group increased significantly during CPB compared with preoperative values. These increases were significantly suppressed in the aprotinin group. 6-Keto-PGF1 alpha (stable metabolite of prostacyclin) increased significantly during CPB in both groups, and there was no significant difference between the two groups. In the aprotinin group, the TXB2/6-Keto-PGF1 alpha ratio decreased significantly during CPB compared with the preoperative value, whereas no significant decrease was observed in the control group. Platelet counts decreased significantly during and after CPB in both groups. Platelet aggregability decreased significantly during CPB in the control group, whereas no significant decrease was found in the aprotinin group. In conclusion, aprotinin treatment improved prostaglandin metabolism and preserved platelet function during open heart surgery.     

Intestinal and arterial plasma thromboxane and prostacyclin levels in shock: effects of indomethacin

The role of thromboxane and prostacyclin in circulatory shock of intestinal origin was investigated in anesthetized dogs by measuring their stable metabolites, thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, respectively, in superior mesenteric vein (SMV), right ventricle (RV), and aorta during superior mesenteric artery occlusion-induced (SMAO) shock and by inhibiting prostanoid synthesis with indomethacin (IM). Release of the SMAO caused a dramatic decrease in mean arterial blood pressure and a significant increase in 6-keto-PGF1 alpha levels in SMV, RV, and aorta within 5 min. Thereafter, 6-keto-PGF1 alpha concentration decreased so that at 60-min postrelease it was not significantly different from the control values. TXB2 levels rose continuously during shock. IM significantly attenuated the magnitude of postocclusion hypotension and reduced both TXB2 and 6-keto-PGF1 alpha production.     

Effect of a thromboxane synthetase inhibitor on eicosanoid synthesis and glomerular injury during acute unilateral glomerulonephritis in the rat

Eicosanoid synthesis was studied in a model of in situ glomerulonephritis (gn) in the rat. Unilateral gn was induced by perfusion of left kidneys with 200 micrograms cationized human IgG followed by intravenous (i.v.) autologous anti-human IgG antiserum. Rats developed proteinuria in the first 24 hours and hypercellular gn with leukocyte infiltration in the left kidney. Synthesis of thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and 6-ketoprostaglandin F 1 alpha(6-keto-PGF 1 alpha) was measured at 6, 12, 18 and 24 hours in isolated glomeruli by radioimmunoassay. In nephritic glomeruli there was a nine-fold rise in TXB2 at six hours (5.35 ng/mg glomerular protein) when compared to control (0.6 ng/mg). TXB2 was still elevated at 24 hours (2.7 +/- 1 ng/mg; control 0.7 +/- 0.2 ng/mg). There were no consistent changes in PGE2 or 6-keto-PGF 1 alpha. No changes were found in right kidneys of nephritic or control rats. Treatment of nephritic rats with a selective thromboxane synthetase inhibitor, dazmegrel (20 mg/kg 8 hourly intraperitoneally), suppressed glomerular TXB2 at 24 hours. TXB2 was also inhibited in right (non-nephritic) kidneys and serum. Dazmegrel did not inhibit proteinuria or glomerular hypercellularity. We conclude there is a major increase in glomerular TXB2 in this model which does not play an essential role in the development of proteinuria or cellular infiltration.     

Unwashed shed blood infusion causes deterioration in right ventricular function after coronary artery surgery

We investigated right ventricular function after infusion of unwashed shed blood collected from mediastinal and chest tube drainage. Changes in thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and prostacyclin respectively, were also investigated. The amount of infused shed blood was 484 +/- 76 ml (mean +/- SD). Right ventricular ejection fraction decreased rapidly after the infusion and did not return to its original level until 120 minutes later (P < 0.05). Mean pulmonary artery pressure rose after infusion of the shed blood (P < 0.05). The TXB2 level in the unwashed shed blood was about 20,000 times higher than the preoperative plasma level. The plasma TXB2 level at 30 minutes after the infusion was significantly elevated (P < 0.05), and at 120 minutes it had returned to the original level. Unwashed shed blood may contain vasoactive substances that induce the release of TXA2 and increase right ventricular afterload.     

Experimental study on the pathophysiology of endotoxin shock as analysed by alterations in thromboxane B2 and 6-keto-PGF1 alpha levels

To evaluate the pathophysiological role of thromboxane A2 (TXA2) in endotoxin shock, plasma concentrations of TXA2 and PGI2 following E. coli endotoxin (ET) administration were measured in dogs and rats by radioimmunoassay of their stable metabolites TXB2 and 6-keto-PGF1 alpha, respectively. Also, the effects of TXA2 synthetase inhibitor (OKY046) on eicosanoid levels, haemodynamics and survival were assessed. The following results were obtained: 1) Survival rates of the rats given 50 mg/kg of ET were 31% at 12 hrs and 17% at 24 hrs. Pretreatment with OKY046 markedly improved the survival rates. 2) Plasma concentrations of TXB2 were rapidly elevated in untreated control dogs and rats following ET administration, whereas plasma 6-keto-PGF1 alpha levels were gradually elevated. TXB2/6-keto-PGF1 alpha ratio showed an early elevation at 15 minutes after ET administration. The ratio became lower than base line, thereafter. 3) In contrast to the controls, animals pretreated with OKY046 did not exhibit significant elevations in plasma TXB2 levels. On the other hand, plasma levels of 6-keto-PGF1 alpha were not altered by OKY046 treatment. 4) In the control dogs given ET, the early elevations in pulmonary artery pressure (PAP) and reduction in lung compliance correlated with the early elevation in plasma TXB2/6-keto-PGF1 alpha ratio. 5) In OKY046-treated dogs, the early elevation in TXB2/6-keto-PGF1 alpha ratio was not seen and PAP increase and lung compliance reduction were prevented. The results suggest that TXA2 plays an important pathophysiological role in the development of endotoxin shock.     

Effect of TXA2 on renal lysosomal membrane

ONO-3708, a thromboxane A2 (TXA2) antagonist, was administered by a double blind method during cardiopulmonary bypass (CPB) to study the changes in the plasma and urinary TXB2 levels. Lysosomal enzyme, urinary N-acetyl-beta-glucosaminidase (NAG) was assessed, in order to investigate the in vivo effect of TXA2 on renal lysosomal membrane. Plasma and urinary TXB2 increased significantly (P less than 0.01) during CPB, showing an increase in TXA2 originating from the kidney, in addition to the increased excretion of platelet derived TXA2 during CPB. Urinary NAG increased significantly (P less than 0.01) in the placebo group during CPB and the value of post CPB increased further more (P less than 0.01). In ONO-3708 2 micrograms.kg-1.min-1 group, urinary NAG slightly but not significantly increased during CPB, but was inhibited significantly (P less than 0.01) as compared with two other groups. As shown above, the increased production of TXA2 appears to inhibit the functions of the renal lysosomal membrane in vivo. Furthermore, ONO-3708 has demonstrated a lysosomal membrane stability effect, and it seems reasonable to expect some antishock effect of this drug.