Prostacyclin reversal of lethal endotoxemia in dogs.
Prostacyclin reversal of lethal endotoxemia in dogs.
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前列环素逆转狗致死性内毒素血症。
DOI：
10.1172/jci110125
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Hechtman,HB
中科院分区：
文献类型：
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作者：
Krausz,MM;Utsunomiya,T;Feuerstein,G;Wolfe,JH;Shepro,D;Hechtman,HB
重度内毒素血症是一种微栓塞和血管内凝血被认为起重要作用的疾病，用前列环素（PGI2）进行实验治疗。在24只狗的研究中，8只注射1.75 mg·kg - 1内毒素的对照动物在24小时内死亡。6只静脉注射100 mg/kg阿司匹林的动物在内毒素30分钟后死亡。10只狗注射100 ng PGI2·kg−1·min−1，持续3 h，注射30 min后存活24 h （P< 0.025）。注射内毒素导致：(a)平均动脉压最大下降62% (P< 0.001)；(b)短暂性平均肺动脉压翻倍（P< 0.001）；(c)心脏指数初始下降70% (P< 0.001)；(d)血小板从213,700降至13,700/mm3(P< 0.001)，白细胞从7,719降至< 750/mm3(P< 0.001)；(e)尿量下降（P< 0.001）；(f)血纤维蛋白原降低34% (P< 0.01)，纤维蛋白降解产物bbb50 μg/ml升高（P< 0.001）；(g)循环组织蛋白酶D滴度升高5倍（P< 0.005）； (h)血中去甲肾上腺素（P< 0.005）、多巴胺（P< 0.005）、肾上腺素（P< 0.001）升高。阿司匹林治疗导致平均动脉压（P< 0.001）和平均肺动脉压（P< 0.005）升高，但心脏指数、尿流量、血小板、白细胞、纤维蛋白降解产物和组织蛋白酶D水平与未治疗对照组相似。pgi2输注后：(a)心脏指数迅速上升至基线水平；(b)停止pgi2治疗后晚期平均动脉压升高（P< 0.005） (c)尿量恢复；(d)循环血小板升高至仍低于基线但高于未治疗对照动物的水平（P< 0.05）；(e)对循环白细胞水平无影响；(f)纤维蛋白降解产物降至11.2 μg/ml (P< 0.05)；(g)组织蛋白酶D水平下降至比未治疗对照组低60% (P< 0.025)；(h) 4 h血浆去甲肾上腺素水平降至基线（P< 0.005）。虽然pgi2的作用方式尚不清楚，但它在实验性内毒素血症的治疗中是有效的。
Severe endotoxemia, a condition where microembolization and intravascular coagulation are thought to play important roles, was treated experimentally with prostacyclin (PGI2). In a study of 24 dogs, 8 control animals injected with 1.75 mg·kg−1of endotoxin died within 24 h. Six animals given intravenous aspirin 100 mg/kg, 30 min after endotoxin died. 9 of 10 dogs infused with 100 ng PGI2·kg−1·min−1for 3 h, given 30 min after the injection of endotoxin survived 24 h (P< 0.025). Injection of endotoxin resulted in a: (a) maximal 62% fall in mean arterial pressure (P< 0.001); (b) transient doubling of mean pulmonary arterial pressure (P< 0.001); (c) initial 70% drop in cardiac index (P< 0.001); (d) decline in blood platelets from 213,700 to 13,700/mm3(P< 0.001), and leukocytes from 7,719 to < 750/mm3(P< 0.001); (e) depressed urine output (P< 0.001); (f) 34% decrease in blood fibrinogen (P< 0.01) and an increase in fibrin degradation products > 50 μg/ml (P< 0.001); (g) fivefold increase in circulating cathepsin D titer (P< 0.005) and (h) increase in blood norepinephrine (P< 0.005), dopamine (P< 0.005), and epinephrine (P< 0.001). Aspirin treatment led to an increase in mean arterial pressure (P< 0.001) and mean pulmonary arterial pressure (P< 0.005), but cardiac index, urine flow, platelets, leukocytes, fibrin degradation products, and cathepsin D levels remained similar to untreated controls. After infusion of PGI2there was a: (a) prompt increase of cardiac index to base-line levels; (b) late increase in mean arterial pressure (P< 0.005) after the discontinuation of PGI2treatment (c) restoration of urine output; (d) increase in circulating platelets to levels still below base line but above untreated control animals (P< 0.05); (e) no effect on circulating leukocyte levels; (f) fall in fibrin degradation products to 11.2 μg/ml (P< 0.05); (g) decline in cathepsin D levels to values 60% lower than the untreated controls (P< 0.025); and (h) reduction in plasma norepinephrine levels to base line at 4 h (P< 0.005). Although the mode of PGI2action is not clear, it is effective in the treatment of experimental endotoxemia.