Effects of recombinant humanen dothelial-derived interleukin-8 on hemorhagic shock in rats

目的：研究重组人内皮细胞衍生的白细胞介素－８（ＩＬ８）对失血性休克的作用．方法：大鼠股动脉放血至ＭＡＢＰ５３２ｋＰａ，维持９０ｍｉｎ，复制晚期失血性休克模型．输血后，静脉注射ＩＬ８２５０μｇ·ｋｇ－１．放免法测定血浆ＥＴ１和６ＫＰＧＦ１α含量．结果：给予ＩＬ８后，ＭＡＢＰ显著提高，休克状态改善，２ｈ存活率相应提高；休克晚期血浆ＥＴ１水平比正常明显升高（２１±４ｖｓ８２±１８ｎｇ·Ｌ－１，Ｐ＜００１），血浆６ＫＰＧＦ１α含量明显降低（１０７±１２ｖｓ１５７±１１ｎｇ·Ｌ－１，Ｐ＜００１）．ＩＬ８显著降低血浆ＥＴ１水平（１０±４ｎｇ·Ｌ－１，Ｐ＜００１），提高血浆６ＫＰＧＦ１α含量（３６８±１６ｎｇ·Ｌ－１，Ｐ＜００１）．结论：ＩＬ８具有较好的抗休克作用．     

非胰岛素依赖型糖尿病患者血浆D-二聚体的变化及其意义

为探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者凝血及纤溶活性，采用ＥＬＩＳＡ双抗体夹心法测定了３５例ＮＩＤＤＭ患者的血浆Ｄ－二聚体。结果：ＮＩＤＤＭ患者血浆Ｄ－二聚体水平为１．６３ｍｇ／Ｌ±０．１４ｍｇ／Ｌ），明显高于正常对照组（０．３３ｍｇ／Ｌ±０．０９ｍｇ／Ｌ）（Ｐ＜０．０５）；有血管病变组Ｄ－二聚体为２．６２ｍｇ／Ｌ±０．６８ｍｇ／Ｌ，高于无血管病变组（０．６９ｍｇ／Ｌ±０．６８ｍｇ／Ｌ），差异有显著性（Ｐ＜０．００１）；血浆Ｄ－二聚体与ＦＢＧ、ＴＣ、ＴＧ相关分析表明Ｄ－二聚体与ＦＢＧ、ＴＧ呈正相关（分别为ｒ＝０．５８，Ｐ＜０．００１；ｒ＝０．０３５，Ｐ＞０．２；ｎ＝１４），与ＴＣ呈负相关（ｒ＝－０．０４５，Ｐ＞０．２，ｎ＝１４）。８例ＮＩＤＤＭ患者治疗后血浆Ｄ－二聚体较治疗前显著降低，分别为１．１１±０．８１，３．６５±１．２２，Ｐ＜０．０５）。提示ＮＩＤＤＭ患者体内存在高凝和继发纤溶活性亢进，血浆Ｄ－二聚体是反映ＮＩＤＤＭ患者高凝和缺血性疾病的诊断、疗效观察的良好指标。     

白芍总甙对B淋巴细胞增殖和白介素1生成的调节作用

白芍总甙（ＴＧＰ）对脂多糖（ＬＰＳ）诱导的小鼠脾淋巴细胞增殖反应的量效曲线呈钟形，用贴壁法除去脾细胞中巨噬细胞（ＭΦ）或加入１０μｍｏｌ·Ｌ１吲哚美辛（Ｉｎｄ）可使ＴＧＰ量效曲线的下降支消失，再加５％同系小鼠腹腔ＭΦ中或前列腺素Ｅ２（ＰＧＥ２）０．０２２０μｍｏｌ·Ｌ１可使量效曲线下降支再现．同步检测ＴＧＰ对ＬＰＳ诱导大鼠腹腔ＭΦ产生ＰＧＥ２与白介素１（ＩＬ１）．结果表明，ＴＧＰ０．５－３ｌ２．５μｇ·ｍＬ１对ＬＰＳ诱导的ＩＬ－１产生曲线呈钟形．而ＴＧＰＬＰＳ的ＰＧＥ２产生曲线呈浓度依赖性地增高；在１２．５－３１２．５μｇ·ｍＬＴＧＰ范围内，１０μｍｏｌ·Ｌ１Ｉｎｄ可使高浓度ＴＣＰＬＰＳ的ＩＬ－１释放曲线明显抬高。提示ＴＧＰ对ＬＰＳ诱导的Ｂ细胞增殖反应和ＩＬ－１诱生的负调节作用都与其促进ＭΦ释放ＰＧＥ２有关．     

烟碱对白细胞介素1β诱导的培养牛脑微血管内皮细胞表达E-选择素的增强作用

目的··：观察烟碱对牛脑微血管内皮细胞（ＢＣＭＥＣ）表达Ｅ－选择素的影响。方法··：离体培养新生牛脑微血管内皮细胞;血细胞计数仪测定ＢＣＭＥＣ粘附大鼠血单核细胞（ＭＮ）的数目;应用ＥＬＩＳＡ法检测ＢＣＭＥＣ表达Ｅ－选择素的量。结果··：高浓度烟碱（１０－５ｍｏｌ·Ｌ－１）单独作用于ＢＣＭＥＣ２ｈ后,使ＢＣＭＥＣ对ＭＮ的粘附率从１２．９％±ｓ０．４％增至１５．７％±ｓ０．６％,且ＢＣＭＥＣ也可表达少量的Ｅ－选择素;而当烟碱与ＢＣＭＥＣ作用２ｈ后,再经白细胞介素１β（ＩＬ－１β）诱导４ｈ,烟碱可浓度依赖性（１０－７ｍｏｌ·Ｌ－１－１０－５ｍｏｌ·Ｌ－１）地增强ＩＬ－１β的诱导作用,增加ＢＣＭＥＣ对ＭＮ的粘附率以及Ｅ－选择素的表达量;抗Ｅ－选择素单克隆（ＡＥｍＡｂ）能显著阻断ＩＬ－１β诱导ＢＣＭＥＣ后对ＭＮ的粘附率。结论··：烟碱增强ＩＬ－１β诱导的脑微血管内皮细胞表达Ｅ－选择素的作用。     

白芍总甙治疗类风湿性关节炎的临床药理研究

对２９例类风湿性关节炎（ＲＡ）患者进行了白芍总甙（ＴＧＰ）的开放性临床试验．结果表明，大剂量ＴＧＰ（１．２～１．８ｇ·ｄ－１）服用８ｗｋ，对ＲＡ患者有明显疗效．不仅改善临床症状与体征以及降低血球沉降率与类风湿因子滴度，而且对ＲＡ患者的异常免疫功能，如外周血单个核细胞产生ＩＬ－１水平；外周血淋巴细胞的致分裂素反应与产生ＩＬ－２水平以及ＩＬ－２受体密度；抑制性Ｔ细胞的数目等均有机能依赖性恢复作用。与氨甲喋呤（ＭＴＸ）的比较试验表明．ＴＧＰ的抗关节炎作用起效较ＭＴＸ早．但疗效较温和，对ＲＡ患者异常免疫功能的影响也不完全相同，且ＴＧＰ的耐受性远较小剂量ＭＴＸ为优。本试验还表明．ＩＬ－１可作为监护ＴＧＰ疗效和调整剂量的一种灵敏而简便的指标。     

松龄血脉康对糖尿病虱血浆一氧化氮、前列环素和内皮素—1水平的影响

目的：研究松龄血脉康对糖尿病（ＤＭ）患者血浆一氧化氮（ＮＯ）、前列环素（ＰＧＩ２）和内皮素－１（ＥＴ－１）水平的影响。方法：６０例２型ＤＭ患者随机分为实验组和对照组,２组一般治疗基本相同。实验组加用松龄血脉康,１．５ｇ,ｔｉｄ。连用１２ｗｋ。测定治疗前后空腹血糖（ＦＢＧ）、糖化血红蛋白Ａ１ｃ（ＧＨｂＡ１ｃ）及血浆ＮＯ、ＰＧＩ２、ＥＴ－１水平。结果：治疗前２组各项指标比较差异无显著性（Ｐ〉０．０５）。治疗后实验组血浆ＮＯ、ＰＧＩ２水平较治疗前显著上升（Ｐ〈０．０１）。ＥＴ－１显著下降（Ｐ〈０．０１）;ＦＢＧ、ＧＨｂＡ１ｃ无明显变化（Ｐ〉０．０５）。对照组治疗前后所有指标均无明显变化（Ｐ〉０．０５）。结论：松龄血脉康可改善ＤＭ虱血管内皮细胞功能,能有效调节ＤＭ患者血浆ＮＯ、ＰＧＩ２、ＥＴ－１水平,对ＤＭ具有一定的辅     

白芍总甙对正常人与类风湿性关节炎患者单核细胞和淋巴细胞功能的影响

０．１～２．５ｍｇ·Ｌ－１白芍总甙（ＴＧＰ）对正常人的ＬＰＳ诱导外周血单个核细胞产生ＩＬ－１．ＰＨＡ－Ｐ诱导淋巴细胞增殖反应和ＩＬ－２产生均呈现浓度依赖性的双向作用；ＴＧＰ还可浓度（０．１～１２．５ｍｇ·Ｌ－１）依赖性地降低正常人淋巴细胞上ＩＬ－２Ｒ的密度．ＴＧＰ能使类风湿性关节炎（ＲＡ）患者低下的ＰＨＡ－Ｐ致分裂素反应与ＩＬ－２产生能力恢复正常，使外周血中减少的Ｔｓ细胞数目回到正常水平．但可使ＲＡ患者ＰＢＭＣ过度产生ＩＬ－１降低至正常范围．并能显著降低ＲＡ患者增高的淋巴细胞ＩＬ－２Ｒ的密度。上述结果表明．ＴＧＰ对ＲＡ患者有明显的机能依赖性免疫调节作用．ＴＧＰ对ＲＡ的治疗作用可能与其调整ＲＡ患者异常的免疫功能有关。     

萘丁美酮代谢物MNAA对人尿褪黑素水平的影响

采用高效液相荧光法（ｅｘλ＝２９５ｕｍ，ｅｍλ＝３４０ｎｍ）同步检测人尿中萘丁美酮（ＮＡＢ）的主要代谢物６－甲氧基－２－萘乙酸（ＭＮＡＡ）及褪黑素（ＭＴ）。５名男性志愿者于１８点口服５００ｍｇＮＡＢ后，尿中ＭＴ累积量仍呈昼夜变化节律，其累积量分别从未服药前的每１２小时２７４．０±５８ｐｍｏｌ（夜晚）和７７．６±２５ｐｍｏｌ（白天）减少至１４５．６±３２ｐｍｏｌ（夜晚）和５０．３±１２ｐｍｏｌ（白天）（Ｐ值均小于０．０１）。依照尿中的ＭＮＡＡ消除速率对中点时间作曲线，求得ＭＮＡＡＴ为２２．５ｈ，ＴＰＫ为１４．２ｈ，与已知报告的血浆中数值相近。相关分析证明，ＭＴ累积量抑制与ＭＮＡＡ消除速率相关（ｒ＝０．９６４４，Ｐ＜０．０５）。ＭＮＡＡ在尿中９６ｈ的累积量仅占口服５００ｍｇＮＡＢ的３．５％，高于ＨａｄｄｏｃｋＲＥ采用同位素得出１％的结论。     

延髓腹外侧头端注射莫索尼定对大鼠血压,心率和肾交感神经放电…

目的：观察延髓腹外侧头端（ＲＶＬＭ）注射莫索尼定（Ｍｏｘ）对麻醉大鼠血压（ＢＰ）、心率（ＨＲ）及肾交感神经放电（ＲＳＮＡ）的影响。方法：麻醉大鼠ＲＶＬＭ注射１μＬ Ｍｏｘ１，１０，１００μｍｏｌ·Ｌ＾－１，同步记录ＢＰ，ＨＲ及ＲＳＮＡ。结果：Ｍｏｘ１，１０，１００μｍｏｌ·Ｌ＾－１分别使ＢＰ从１３．９±１．０ｋＰａ降至１３．０±１．７ｋＰａ（Ｐ〈０．０５），１３．８±１．８ｋＰａ至１１．４±１．５     

黄芪多糖对烧伤小鼠细胞免疫功能的作用

应用小鼠烧伤模型，对黄芪多糖（ＡＰＳ）的免疫增强作用进行了体内外研究。结果表明：体内应用ＡＰＳ（２５０ｍｇ·ｋｇ－１，ｑｄ，连续５ｄ），可明显提高烧伤小鼠Ｔ淋巴细胞转化，ＩＬ－２的产生及ＩＬ－２Ｒ的表达；体外分别应用５０、１００、２５０ｍｇ·Ｌ－１的黄芪多糖，发现其可纠正烧伤小鼠Ｔ淋巴细胞转化，ＩＬ－２的产生及ＩＬ－２Ｒ表达的受抑状态，并促进巨噬细胞产生ＩＬ－１，抑制ＰＧＥ２合成，且呈剂量依赖关系；体外去除烧伤小鼠脾细胞中的巨噬细胞后，ＡＰＳ对Ｔ淋巴细胞转化，ＩＬ－２产生及ＩＬ－２Ｒ表达的调节作用消失。提示ＡＰＳ对烧伤小鼠的免疫调节作用依赖于巨噬细胞，通过调节其分泌ＩＬ－１，抑制ＰＧＥ２合成，而促进ＩＬ－２产生及ＩＬ－２Ｒ表达，进而增强Ｔ淋巴细胞增殖。     

地塞米松,噻庚啶,山莨菪碱和地诺前列酮对内毒素休克TNFα产？…

目的：研究地塞米松（Ｄｅｘ）噻庚啶（Ｃｙｐ）,山莨菪碱（Ａｎｉ）和地诺前列腺酮（Ｄｉｎ）对脂多糖（ＬＰＳ）诱导的肿瘤坏死因子（ＴＮＦα）,基因表达的影响和抑制ＴＮＦ,产生的抗体休克作用。方法：Ｗｉｓｔａｒ大鼠静脉注射ＬＰＳ（ＥｃｏｌｉＯ１１１Ｂ４,５ｍｇ．ｋｇ＾－１）复制内毒素休克模型,Ｎｏｒｔｈｅｒｎ印迹杂交分析肝脏ＴＮＦαｍＲＮＡ表达,放射免疫法测定血浆ＴＮＦα的含量。结果：ＬＰＳ攻击后２ｈ肝     

Beneficial actions of RO 15-1788, a benzodiazepine receptor antagonist, in hemorrhagic shock

We studied RO 15-1788, a new benzodiazepine receptor antagonist, [ethyl 8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo (1, 5a) (1, 4) benzodiazepine-3-carboxylate] to determine its effects in a murine model of hemorrhagic shock. Hemorrhaged rats treated with RO 15-1788 maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values compared to rats receiving only the vehicle (final MABP 114 +/- 4 vs 82 +/- 4 mmHg, p less than 0.001). Moreover, RO 15-1788 decreased the release of the lysosomal hydrolase, cathepsin D (p less than 0.02) into the circulation and blunted the plasma accumulation of free amino-nitrogen groups (p less than 0.01). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in RO 15-1788 treated rats subjected to hemorrhagic shock than in those given the vehicle (18 +/- 2 vs 42 +/- 4 U/ml, p less than 0.01). Additionally, in vitro analysis indicated that RO 15-1788 antagonizes PAF induced coronary vasoconstriction and cardiac depression observed in perfused rat hearts, as well as inhibiting PAF induced platelet aggregation in cat platelet rich plasma. Our results suggest that antagonism of PAF actions can contribute significantly to the beneficial effects of RO 15-1788 in hemorrhagic shock.     

cGMP介导以注入L—精氨酸诱导的大鼠血管加压素释放效应

目的：探讨ｃＧＭＰ是否介导Ｌ－精氨酸（一氧化氮合酶物）引起的血管加压素（ＡＶＰ）释放增多效应。方法：用放射免疫法测定大鼠血浆中ＡＶＰ水平。结果：侧脑室分别注射Ｌ－精氨酸和８－溴－ｃＧＭＰ（一种可透过膜的ｃＧＭＰ衍生物）能刺激血浆ＡＶＰ水平增加［分别从（３．２±０．５）升至（５．８±１．４）ｎｇ·Ｌ＾－１，从（２．６±０．３）升至６６．６±０．４）ｎｇ·Ｌ＾－１，Ｐ〈０．０１］，同时注射Ｌ－精氨酸和     

肝素对生长因子诱导的大鼠肺动脉平滑肌细胞分裂和增殖的影响

目的：探讨肝素是否能抑制生长因子诱导的大鼠肺动脉平滑肌细胞（ＰＡＳＭＣ）分裂和增殖。方法：应用含１０％ＦＢＳ的Ｍ－１９９培养液培养大鼠ＰＡＳＭＣ。细胞分裂及细胞增殖分别用［ｍｅｔｈｙｌ－＾３Ｈ］ＴｄＲ和细胞计数监测。结果：ＦＢＳ（１０％），以及ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ＾－１），ＦＧＦ（５０μｇ·Ｌ＾－１），或ＩＬ－１α（１００ｎｇ·Ｌ＾－１）联合应用均能增加大鼠ＰＡＳＭＣ分裂。肝素（     

Beneficial action of a new opiate antagonist (Win 44,441-3) in hemorrhagic shock

The new opiate antagonist Win 44,441-3 (-)-isomer was infused intravenously in cats at a rate of 2 mg . kg-1 . h-1 to determine its effect in hemorrhagic shock. Hemorrhaged cats treated with Win 44,441-3 maintained post reinfusion mean arterial blood pressure (MABP) at a higher value compared to cats receiving only the vehicle. Final MABP was 70 +/- 11 mm Hg for cats receiving vehicle compared to 103 +/- 7 mm Hg for cats receiving Win 44,441-3. These values represent 60 +/- 9% and 85 +/- 6% of initial MABP for the vehicle- and Win 44,441-3-treated cats respectively. Win 44,441-2 (+)-isomer, the inactive stereoisomer of Win 44,441-3, was also infused at 2 mg . kg-1 . h-1 in cats subjected to hemorrhagic shock. The final pressure in this group was 72 +/- 8 mm Hg which is 61 +/- 8% of the initial pressure for this group. Win 44,441-3 and Win 44,441-2 were both ineffective in moderating increases in circulating lysosomal hydrolase activity in shocked cats. Neither isomer stabilized lysosomal membranes or retarded proteolysis in vitro. Plasma myocardial depressant factor was significantly reduced by the opiate antagonist, Win 44,441-3 during shock. Our results show that the systemic infusion of an opiate antagonist improves the hemodynamic state of cats subjected to hemorrhagic shock while the (+)-isomer which lacks opiate antagonist activity produces no such improvement.     

Protective actions of S-nitroso-N-acetylpenicillamine (SNAP) in a rat model of hemorrhagic shock.

The anti-shock effects of an organic nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), were tested in a rat model of hemorrhagic shock. Administration of SNAP at a dose of 10 mcg/kg injection followed by 10 mcg/kg/h infusion neither significantly decreased mean arterial blood pressure (MABP) nor significantly altered bleedout volumes in hemorrhagic rats, indicating that SNAP did not modify the severity of the shock protocol. However, hemorrhaged rats treated with SNAP maintained post-reinfusion MABP at significantly higher values than hemorrhaged rats receiving 0.9% NaCl (final MABP 81 +/- 3.0 mmHg vs. 54 +/- 1.1 mmHg, respectively; p < 0.001). SNAP also significantly increased survival times following hemorrhagic shock (113 +/- 4 min in SNAP treated rats compared with 70 +/- 4.5 min in vehicle treated rats, p < 0.001). The overall survival rates were 87.5% when treated with SNAP and 0% with 0.9% NaCl (p < 0.01). In hemorrhagic shock rats receiving only vehicle, a significant accumulation of neutrophils in intestinal tissue occurred as indicated by a higher MPO activity in intestinal tissue (MPO activity, 1.26 +/- 0.31 vs. 0.14 +/- 0.05U/100 mg in sham hemorrhagic shock rats, p < 0.02). Administration of SNAP significantly attenuated the neutrophil accumulation in the intestinal tissue (MPO activity, 0.42 +/- 0.09U/100 mg, p < 0.05 compared with hemorrhagic rats receiving only the vehicle). Moreover, endothelial dysfunction of superior mesenteric artery rings occurred in hemorrhagic shock rats given only 0.9% NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ghrelin对败血症休克的影响(英文)

目的:研究ghrelin对大鼠晚期败血症休克的防治作用。方法:用盲肠结扎并穿刺法制备大鼠败血症休克模型,在术后即刻和8小时分别从股静脉和皮下注射ghrelin 10 nmol/kg。术后18h测定大鼠的血流动力学指标、血浆ghrelin、乳酸、葡萄糖浓度及心肌ATP含量。结果:与败血症休克组比较,ghrelin治疗组大鼠血压升高了33％,+LVdp/dt_(max)和-LVdp/dt_(max)值分别增加了27％和33％,而LVEDP降低了33％,血糖水平升高了54％,血浆乳酸浓度降低了40％,心肌ATP含量增加了22％(P<0.01)。死亡率由44％降到25％。败血症休克大鼠血浆ghrelin水平比假手术组(149±23)pmol/L增加了51％(P<0.01),血浆ghrelin水平与动脉血压和血糖值呈显著负相关(相关系数分别为-0.721和-0.811,P<0.01)。结论:ghrelin治疗可以部分纠正败血症休克大鼠的血流动力学紊乱和代谢障碍。     

Salutary effects of nitrendipine, a new calcium entry blocker, in hemorrhagic shock

Intracellular accumulation of calcium is thought to play an integral role in the progression of ischemic injury and cell death. We infused the calcium entry blocker, nitrendipine (1.5 micrograms/kg per min), into cats in order to investigate the importance of extracellular Ca2+ influx during hemorrhagic shock. Nitrendipine proved to be a potent hypotensive agent in sham shock cats when infused over a 4 h period (156 +/- 9 to 90 +/- 5 mm Hg) (P less than 0.01). However, in hemorrhaged animals, nitrendipine treatment maintained the post-reinfusion MABP at a significantly higher (P less than 0.01) value than untreated controls (79 +/- 5 vs. 51 +/- 4 mm Hg, respectively). Superior mesenteric artery flow (SMAF) for hemorrhaged animals treated with nitrendipine was significantly higher (9.8 +/- 1.4 ml/min per kg) (P less than 0.01) than that for untreated cats (4.2 +/- 0.4 ml/min per kg), at 2 h post reinfusion. There was no significant increase in SMAF during oligemia in the nitrendipine-treated animals. Nitrendipine was also found to significantly retard the appearance of cathepsin D in the plasma of hemorrhaged cats as well as reduce plasma proteolysis to values not significantly different from sham shock animals. Furthermore, myocardial depressant factor (MDF) activity in the plasma of nitrendipine-treated shock cats was not significantly different from sham shock animals, while the plasma MDF activity for shock cats receiving vehicle increased 3-fold (P less than 0.001). The beneficial effects for nitrendipine in hemorrhagic shock are likely due to both its vasodilator function and its ability to reduce intracellular Ca2+ accumulation during ischemia, thereby reducing disruption of cell membrane systems.     

金属硫蛋白对大鼠硝酸甘油耐药性的影响(英文)

目的:评价金属硫蛋白(metallothionein, Met)在体内是否能改善硝酸甘油耐药的发生。方法:大鼠给予硝酸甘油(nitroglycerin, Nit)贴剂治疗两天(0.05 mg·h~(-1))以产生耐药。于耐药大鼠预先给予ZnCl_2以诱导内源性Met的合成及给予外源性Met15 mg·kg~(-1)·d~(-1)连续2 d。结果:Nit ZnCl_2组大鼠肝脏、血浆Met明显高于对照组(C组)。Nit组大鼠离体主动脉环的舒张反应最低。Nit ZnCl_2组大鼠及Nit Met组大鼠对SNP的降压反应明显强于Nit组。结论:外源性Met或内源性诱导合成的Met可以改善大鼠Nit耐药的发生。     

Salutary consequences of blockade of platelet activating factor in hemorrhagic shock

We studied the effects of a potent, specific platelet activating factor (PAF) antagonist, CV-6209, in a murine model of hemorrhagic shock. Hemorrhaged rats treated with CV-6209 (1 mg/kg) maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values than rats receiving either 0.9% NaCl or a lower dose (0.2 mg/kg) of CV-6209 (final MABP 88 +/- 4 vs. 57 +/- 4, vs. 61 +/- 7 mm Hg, respectively). CV-6209 (1 mg/kg) also significantly attenuated the increase in plasma cathepsin D activity following hemorrhage compared with hemorrhaged rats receiving only its vehicle (i.e. 0.9% NaCl). CV-6209 (1 mg/kg) also significantly decreased the plasma accumulation of free amino-nitrogen compounds and the plasma activity of a myocardial depressant factor (MDF) compared to hemorrhaged rats receiving 0.9% NaCl. Rats receiving CV-6209 (1 mg/kg) exhibited a significantly increased survival rate and survival time post-reinfusion compared to rats receiving only the vehicle. These data indicate that PAF is an important mediator of hemorrhagic shock in the rat and that PAF receptor antagonists may be useful in hemorrhagic shock states.