Improvement in organ blood flow by inhibition of thromboxane synthetase during experimental endotoxic shock in the rat.
Improvement in organ blood flow by inhibition of thromboxane synthetase during experimental endotoxic shock in the rat.
复制标题
在大鼠实验性内毒素休克期间通过抑制血栓素合成酶改善器官血流。
DOI：
10.1097/00005344-198605000-00012
复制
发表时间：
1986
影响因子：
3
通讯作者：
Corral,D
中科院分区：
文献类型：
--
作者：
Tempel,GE;Cook,JA;Wise,WC;Halushka,PV;Corral,D
内源性休克与花生四烯酸代谢血栓素（Tx）和前列腺素增加有关。本研究考察了两种结构不同的（Tx）合成酶抑制剂对肠道沙门氏菌内毒素（LPS）（15 mg/kg）诱导的龙-埃文斯大鼠心输出量和器官血流量的影响。将咪唑衍生物7（1-咪唑基）庚酸（7- iha）和-(E)-3-[4-（3-吡啶基甲基）苯基]-2-甲基丙烯酸钠（OKY-1581）分别以30 mg/kg和5 mg/kg的剂量静脉注射于内毒素注射前30 min。在轻度乙醚麻醉下，用Sr-85标记微球评估lps后30分钟的心血管功能。注射内毒素使心输出量减少60%（对照组34.0+/-2.7 ml/min/100 g体重），收缩压降低38.9%。两种Tx合成酶抑制剂均能显著（p< 0.05）减轻心输出量的减少，但只有7-IHA能改善血压。7-IHA或OKY-1581预处理显著（p< 0.05）减轻lps诱导的肾灌注减少。休克后肺营养血流量（1.1+/-0.2 ml/min/g肺）下降近70%。两种Tx合成酶抑制剂都阻止了这种减少。LPS休克导致大约30%的脑血流量减少。7-IHA显著（p< 0.05）改善血流，而OKY-1581无明显作用。7-IHA和OKY-1581同样改善了内脏血流。两种抑制剂治疗后，肝血流量均恢复到对照组的水平，比休克对照组低55% （p< 0.05）。同样，7-IHA和OKY-1581预处理后的胃肠道灌注比对照组减少了70%，分别改善了110%和65%。这些观察结果暗示Tx可能在内毒素休克早期介导全身缺血和心血管功能障碍的发展中起作用。
Endotoxic shock is associated with increased metabolism of arachidonic acid to thromboxane (Tx) and prostaglandins. This investigation examined the effects of two structurally dissimilar inhibitors of (Tx) synthetase on Salmonella enteritidis endotoxin (LPS)(15 mg/kg)-induced alterations in cardiac output and organ blood flow in Long-Evans rats. An imidazote derivative, 7 (1-imidazolyl) heptanoic acid (7-IHA), and sodium-(E)-3-[4-(3-pyridyl-methyl) phenyl]-2-methacrylate (OKY-1581) were injected intravenously at 30 and 5 mg/kg, respectively, 30 min before injection with endotoxin. Cardiovascular function was assessed 30 min post-LPS with Sr-85 labeled microspheres under light ether anesthesia. Injection of endotoxin caused a 60% decrease in cardiac output (34.0+/-2.7 ml/min/100 g body weight in control rats) and a 38.9% decrease in systolic arterial pressure. Both Tx synthetase inhibitors significantly (p< 0.05) attentuated the decrease in cardiac output, although only 7-IHA improved blood pressure. Pretreatment with 7-IHA or OKY-1581 significantly (p< 0.05) attenuated the LPS-induced decrease in renal perfusion. Lung nutrient blood flow (1.1+/-0.2 ml/min/g lung) decreased nearly 70% in shock. Both Tx synthetase inhibitors prevented this reduction. LPS shock resulted in approximately a 30% decrease in brain blood flow. 7-IHA significantly (p< 0.05) improved flow, while OKY-1581 was without apparent effect. Splanchnic blood flow was likewise improved by 7-IHA and OKY-1581. Liver blood flow, 55% less than values of the control group in shock (p< 0.05), was returned to values of the controls by both inhibitors. Similarly, gastrointestinal perfusion, 70% less than values of the control group in shock, was improved 110% and 65% by 7-IHA and OKY-1581 pretreatment, respectively. These observations implicate a possible role for Tx in mediating systemic ischemia and the development of the cardiovascular dysfunction in early endotoxin shock.