6-keto-PGF1 alpha levels and prostacyclin therapy in 2 adult patients with hemolytic-uremic syndrome

Evidence supports the hypothesis that plasma prostacyclin activity is deficient in hemolytic-uremic syndrome (HUS). We studied 2 adult patients with HUS. Plasma levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Both patients were found to have elevated 6-keto-PGF1 alpha levels. These findings are in contradiction with the prostacyclin deficiency hypothesis and with earlier reports of low or undetectable plasma levels of this metabolite. The patients were treated with IV prostacyclin after a single plasma exchange. The first patient, admitted with advanced renal failure, obtained a rapid remission but renal function did not recover; the second patient, admitted with a less pronounced degree of renal failure, reacted slowly to therapy but renal function partially recovered. We believe that, if any benefit is to be expected from prostacyclin therapy in HUS, it should be started early in the course of the disease.     

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.     

高位硬膜外阻滞对猪急性心肌缺血/再灌注损伤时血浆TXB2和6-keto-PGF1α水平的影响

目的探讨0.5%布比卡因高位硬膜外阻滞对急性心肌缺血/再灌注损伤时血栓素B2(TXB2)和6-酮-前列腺素F1α(6-keto-PGF1α)的影响.方法健康雄性家猪20只,体重(23.0±2.5)kg,随机分为布比卡因组(Ⅰ组)、生理盐水组(Ⅱ组).静注10mg.kg-1硫喷妥钠后,气管插管,静点琥珀胆碱和芬太尼控制呼吸,维持麻醉.T3～4穿刺置入硬膜外导管,按分组分别硬膜外注射0.5%布比卡因和生理盐水各2ml,15min后结扎左冠脉前降支40min.分别在给药前和结扎40min时、开放后1h、3h、5h抽取右心房血,测定血浆TXB2、6-keto-PGF1α的浓度.给药前所测定的心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)作为基础值.结果Ⅱ组各时点血液动力学无明显变化,Ⅰ组HR、MAP和CVP分别下降22%、25%和28%.两组再灌注后1h、3h及5h TXB2、TXB2/6-keto-PGF1α比值逐渐升高,且均显著高于给药前和结扎40min.Ⅰ组升高程度显著低于Ⅱ组(P＜0.05).而6-keto-PGF1α组内组间比较,变化趋势与TXB2恰相反.Ⅰ组有1只因室颤而死亡,Ⅱ组有4只(P＜0.05).结论心肌缺血/再灌注损伤与TXB2和6-keto-PGF1α有一定关系,高位硬膜外阻滞通过调节缺血/再灌注后血栓素A2和前列环素的平衡在一定程度上减轻了心肌缺血/再灌注损伤.     

Increased plasma PGE2, 6-keto-PGF1 alpha, and 12-HETE levels following experimental concussive brain injury

Previous investigations have shown that brain prostaglandin levels are transiently elevated following experimental fluid percussion brain injury. Associated with these increased prostaglandin levels there is free radical production and abnormalities in cerebral arteriolar function. The purpose of this study was to determine whether experimental fluid percussion brain injury in cats is associated with increased systemic levels of prostaglandins and the lipoxygenase product, 12-HETE. Blood samples were collected before and at various periods of time after 2.7 atm of fluid percussion brain injury was produced in adult cats. Prostaglandin and 12-HETE analysis was performed by radioimmunoassay after extraction of the plasma samples. The control levels for 6-keto-PGF1 alpha, PGE2, and 12-HETE were 477 +/- 42, 2,372 +/- 431, and 13,328 +/- 1,769 pg/ml, respectively. Following injury all three eicosanoids reached peak plasma levels by 1-5 min after injury. The percentile increases for all eicosanoids were similar and increased from 70 to 110%. The increases were sustained at up to 30 min postinjury and by 1 h after injury were at control levels. As in previous studies, hypertension following injury was maximal by 1 min postinjury and blood pressure had returned to near normal levels by 5 min postinjury. These studies demonstrate prolonged systemic increases in eicosanoids following injury. Since free radical production and vascular damage occur concomitantly with eicosanoid production, the prolonged increases in these products suggest that there is an attainable therapeutic window following injury during which administration of free radical scavengers may decrease radical damage and reduce the consequences of injury.     

单穴电针对腰椎间盘突出症患者腰腿痛及外周血血栓素B2、前列环素的影响

目的:探讨电针治疗腰椎间盘突出症的有效方法及其外周促循环镇痛机制。方法:将98例腰椎间盘突出症按入组先后随机分成治疗组(53例)与对照组(45例),分别给予局部单穴电针与常规取穴电针治疗(共8次),观察电针前后疼痛程度变化(共9次),以及血栓素B2血浆(TXB2)、前列环素(6-keto-PGF1α,6-K)和T/K比值的变化(共2次)。结果:两组治疗后患者疼痛程度均明显减轻(P<0.001),但治疗组比对照组更明显,存在着组间差异(P<0.001)。治疗结束后两组外周血TXB2和T/K比值均显著降低(P<0.001),而6-K则显著升高(P<0.001),各项指标治疗组比对照组变化更明显,存在着组间差异(P<0.001)。结论:局部单穴电针疗法对腰椎间盘突出症较常规取穴电针有更好的临床疗效,其作用机制可能与良性调节患者外周血TXB2、6-X及其T/K有关。     

吸入麻醉药对人血浆和血小板血栓素B2生成与血小板聚集的影响

目的：探讨吸入麻醉剂氟烷、安氟醚和异氟醚对人血浆血栓素Ｂ２（ＴＸＢ２），血小板ＴＸＢ２生成与血小板聚集的影响。方法：血浆ＴＸＢ２和血小板ＴＸＢ２的生成量用放免分析法测量，血小板聚集率用比浊法测量。结果：吸入１ＭＡＣ氟烷３０分钟后，血浆ＴＸＢ２浓度、二磷酸腺苷（ＡＤＰ）和肾上腺素（Ｅ）诱导的血小板ＴＸＢ２生成量与血小板聚集率显著下降，吸入１ＭＡＣ安氟醚３０分钟后，血浆ＴＸＢ２浓度和血小板ＴＸＢ２生成量与血小板聚集率亦显著下降，其降低的程度比氟烷轻。吸入１ＭＡＣ异氟醚对上述指标无明显影响。血小板ＴＸＢ２生成的减少与血小板聚集率的下降呈显著正相关。结论：氟烷显著抑制血小板聚集，安氟醚次之，异氟醚对血小板聚集无明显影响。其机制可能与氟烷和安氟醚通过抑制血小板上血栓素Ａ２受体的亲和力，降低ＡＤＰ和Ｅ诱导的血小板ＴＸＢ２的生成有关。     

针刀疗法对L3横突综合征兔血浆血栓素B2及6-酮-前列腺素水平的影响

目的:观察针刀疗法对L3横突综合征兔血浆TXB2、6-keto-PGF1α水平的影响.方法:将实验兔18只随机分为针刀干预组、模型对照组、正常对照组,每组6只,于造模后10 d、15 d、25 d、30 d检测结果,进行统计学分析.结果:针刀干预组10 d、15 d、25 d、30 d TXB2含量与模型组比较差异无显著性(P>0.05),6-keto-PGF1α含量、TXB2/6-keto-PGF1α比值与模型组差异有非常显著性(P<0.01).结论:针刀干预使6-keto-PGF1α、TXB2/PGF1α比值呈良性改变,从而改善局部微循环,促进炎症吸收,增强了组织修复再生能力.     

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.     

活血化瘀中药对激素性股骨头坏死血浆TXB2与6-keto-PGF1α影响的实验研究

目的：探讨活血化瘀法在激素性股骨头坏死的治疗作用。方法：用内毒素加激素注射造成兔股骨头坏死，测定其血浆TXB2和6-keto-PGF1α的动态变化，以此作为血瘀证的观察指标。结果：光镜观察示模型组股骨头骨小梁变细、空骨陷窝增加，成骨细胞数量减少，并出现TXB2与6-keto-PGF1α比值失平衡，这些表现随着时间的推移逐渐加重；而用复方生脉成骨胶囊治疗能逆转股骨头坏死，保护血管内皮，恢复TXB2与6-keto-PGF1α的平衡。结论：激素性股骨头坏死与血瘀证之间有密切关系，用活血化瘀中药可防止股骨头坏死的发展。     

Influence of pressure, flow rate, and pulsatility on release of 6-keto-PGF1 alpha and thromboxane B2 in ex vivo-perfused canine veins

The influence of pressure, flow, and pulsatility on the release of prostacyclin (measured as 6-keto-PGF1 alpha) and thromboxane (measured as TxB2) was assessed in canine jugular veins perfused ex vivo with Hanks' balanced salt solution for five consecutive 15-minute periods. Control segments were perfused at 7 mm Hg with nonpulsatile flow at a rate of 90 ml/min, whereas experimental segments were perfused with pulsatile flow as well as nonpulsatile flow at pressures of 50 or 100 mm Hg and flow rates of 60 or 130 ml/min. Prostacyclin release from control segments during the first 15-minute period was 49.5 +/- 7.4 pg/mm2/15 min, which declined to 13.9 +/- 2.5 pg/mm2/15 min after 60 minutes (p less than 0.002). Arachidonic acid stimulation during the last 15-minute perfusion period increased the release to 56.1 +/- 9.4 pg/mm2/15 min (p less than 0.002). Thromboxane release from control segments was initially 4.4 +/- 1.2 pg/mm2/15 min, which declined to 0.8 +/- 0.2 pg/mm2/15 min after 60 minutes (p less than 0.002), and subsequently increased with arachidonic acid stimulation to 1.3 +/- 0.1 pg/mm2/15 min (p less than 0.01). In contrast to control perfusion conditions, changes in nonpulsatile flow rates did not affect prostacyclin release, whereas thromboxane release was lower when perfused at 60 ml/min. Pressures of 50 and 100 mm Hg increased the initial release of prostacyclin. Similarly, pulsatile flow enhanced prostacyclin release at both low and high pressures, being more pronounced with the latter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial 6-keto-PGF1 alpha and TxB2 release in ex vivo perfused canine vessels: effects of pulserate, pulsatility, altered pressure and flow rate

Certain experimental conditions are known to influence the release of prostacyclin and thromboxane from the vessel wall. The specific effects of altered pulsatility, pressure, and flow rate on intraluminal release of 6-keto-PGF1 alpha and thromboxane B2 were assessed in canine arteries perfused ex vivo for five 15 min periods with arachidonic acid (AA) added during the last period. Control arteries were perfused at 100 mmHg with pulsatile flow of 90 ml/min. Experimental arteries were perfused at 7, 50 and 200 mmHg with pulsatile flow of 90 ml/min, and at 100 mmHg pressure with pulsatile flow of 20, 60, 130 and 180 ml/min, as well as at 100 mmHg with 90 ml/min nonpulsatile flow. Perfusion pump rates of 44 and 96 beats/min were also assessed. The lowest perfusion pressure, 7 mmHg, resulted in a lesser initial release of prostacyclin compared to higher pressures, and there was a tendency to a higher release of prostacyclin with increasing pressures. There was also a tendency for a lesser response to AA in arteries perfused at 200 mmHg, perhaps due to endothelial cell damage. Nonpulsatile flow was associated with a decreased initial release of prostacyclin, and diminished release following addition of AA when compared to pulsatile flow. Altered flow rate elicited no difference in prostacyclin release, although there was a tendency towards a lesser release when perfused at 20 ml/min compared to 130 ml/min or 180 ml/min. Thromboxane release was decreased by nonpulsatile flow but was otherwise unaffected by the experimental conditions tested. It is concluded that pulsatility enhances release of prostacyclin from arteries.(ABSTRACT TRUNCATED AT 250 WORDS)     

骨科大手术前后血浆ET、TXB2、6-Keto-PGF1a的变化及其意义

目的：探讨骨科大手术前后血浆ET、TXB2和6-Keto-PGF1a的变化及其对监测DVT发生的意义。方法：对48例骨科大手术患者术前24h、术后24h和72h分别进行血浆ET、TXB2和6-Keto-PGF1a测定。结果：有9例并发DVT,其术前24h与术后24h和72h的ET、TXB2和6-Keto-PGF1a检测结果有显著性差异（P〈0.05）;并发DVT组与未并发DVT组比较,术前ET、TXB2和6-Keto-PGF1a检测结果无显著性差异（P〉0.05）,术后24h、72h有显著性差异（P〈0.05）。结论：血浆ET、TXB2和6-Keto-PGF1a动态监测,对骨科大手术后并发DVT具有早期诊断价值。     

氟烷、安氟醚、七氟醚肝毒性与TXB_2、6－keto－PGF（1α）含量变化（氟烷性肝炎的研究Ⅲ）

雄性ＳＤ大鼠饮用含苯巴比妥钠（１ｍｇ／ｍｌ）的饮水１周后，随机分为四组，每组８例，分别吸入：Ｃ，１４％Ｏ＿２／８６％Ｎ＿２；Ｅ，１４％Ｏ＿２／８６％Ｎ＿２／１．２ＭＡＣ安氟醚；Ｓ，１４％Ｏ＿２／８６％Ｎ＿２／１．２ＭＡＣ七氟醚；Ｈ，１４％Ｏ＿２／８６％Ｎ＿２／１．２ＭＡＣ氟烷１ｈ。２４ｈ后发现Ｈ组血浆ＡＬＴ活性显著高于其它各组，并有明显的小叶中心性肝细胞坏死及汇管区炎细胞浸润，血窦重度充血。Ｅ组可见部分肝小叶内有小叶中心性坏死及空泡变性。Ｈ组肝匀浆及血浆中ＴＸＢ＿２含量显著高于其它各组。６－ｋｅｔｏ－ＰＧＦ１ａ各组间均无显著差异。提示氟烷性肝炎与ＴＸＡ＿２／ＰＧＩ＿２平衡失调有一定的关系。     

Changes in urinary immunoreactive-TXB2 and 2,3-dinor TXB2 in man following cardiopulmonary bypass

We measured urinary levels of i-TXB2, 2,3-dinor TXB2 and NAG following cardiopulmonary bypass (CPB) and studied their clinical significance. Subjects studied were 8 patients undergoing cardiac surgery. In the CABG group, urinary i-TXB2, 2,3-dinor TXB2 and NAG level increased significantly (P less than 0.05) 3hrs after CPB, but decreased on and after the 1st postoperative day. In the DVR group, these levels showed similar changes, but i-TXB2 and NAG levels were significantly (P less than 0.05) higher than those of the CABG on the 1st or 3rd postoperative day. A significant correlation (r = 0.84, P less than 0.05) was observed between NAG and i-TXB2 on and after 2nd postoperative day. The results suggest that urinary i-TXB2 during the period immediately after CPB is derived from platelets and reflects the functional changes in renal urinary tubules, while urinary i-TXB2 level on and after the 2nd postoperative day reflects the function of the renal urinary tubules.     

Changes in arterial thromboxane B2 and 6-keto-prostaglandin-F1 alpha levels in cirrhotic and non-cirrhotic patients after hepatectomy

Following hepatectomy, arterial concentrations of thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), which are stable metabolites of thromboxane A2(TXA2) and prostaglandin I2(PGI2), were measured by radioimmunoassay in 17 cirrhotic and 9 non-cirrhotic patients to assess the role of TXB2 and PGI2 in patients with liver dysfunction during hepatectomy. In both cirrhotic and non-cirrhotic patients, arterial TXB2 and 6-keto-PGF1 alpha levels significantly increased during hepatectomy and decreased to preoperative levels at the 1st postoperative day (1-POD). The TXB2/6-keto-PGF1 alpha ratio significantly decreased during hepatectomy and at 1-POD. There were no significant differences in changes of TXB2 and PGI2 levels between cirrhotic and non-cirrhotic patients. In cirrhotic patients with poor hepatic reserve, whose ICG K values were less than 0.08, arterial 6-keto-PGF1 alpha levels were significantly higher and the ratio were significantly lower than in cirrhotic patients with good hepatic reserve and non-cirrhotic patients before and after operation. Based on these results, it is concluded that the TXA2/PGI2 ratio becomes low after hepatectomy and the ratio is lower in cirrhotic patients with poor hepatic reserve.