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Vascular Reactions in Septic Shock and Multiple Organ Failure

感染性休克和多器官衰竭中的血管反应

基本信息

批准号：
14571453
负责人：
TSUNEYOSI Isao
金额：
$ 1.66万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

We investigated vascular reactions in human arteries, such as gastro-epiploic arteries, internal mammary arteries, and radial arteries, obtained from patients who were undergoing coronary artery bypass surgery(CABG).1)Systematic investigations of the actions of phosphodiesterase(PDE)3 inhibitors on different human vascular tissues have not been performed. Our results suggest different activities among the three PDE3 inhibitors in human arteries located in different regions. Moreover, these drugs differ in their potencies against the contractile responses to agonists such as NE and thromboxane A_2 in these arteries.2)The direct actions of dopamine on human arterial coronary bypass grafts are not well known. We investigated its effects on isolated rings cut from radial arteries(RA), gastroepiploic arteries(GEA), and internal mammary arteries(IMA) harvested from patients undergoing coronary artery bypass surgery. Our results suggest that differing affinities of the drug for DA_1- and α_1-adrenergic receptors may underline its variable contractile and vasorelaxing effects among these arteries.3)We investigated the direct effect of dexmedetomidine(DEX) on human resistance arteries in vitro. Gastroepiploic arteries were isolated from the omentum of gastrectomy specimens, the vascular endothelium was denuded, and the smooth muscle mechanical responses were measured. Our results indicate that DEX has dual α_2-adrenergic agonist and α_1-adrenergic antagonist actions in human isolated gastroepiploic arteries. The data presented here predict that DEX would have little direct effect on vascular reactivity under normal clinical conditions where steady-state plasma levels of DEX are generally less than 10^<-7> M. However, the direct α_2 agonist and α_1 antagonist actions observed with higher concentrations of DEX could significantly affect vascular tone under certain conditions.

我们研究了从接受冠状动脉旁路手术（CABG）的患者中获得的人体动脉（如胃网膜动脉、内乳动脉和桡动脉）的血管反应。1）尚未对磷酸二酯酶（PDE）3抑制剂对不同人体血管组织的作用进行系统研究。我们的研究结果表明，三种PDE 3抑制剂在人体动脉中的不同部位具有不同的活性。此外，这些药物对NE和血栓素A_2等激动剂引起的收缩反应的抑制作用也不同。2）多巴胺对人动脉冠状动脉搭桥术的直接作用尚不清楚。我们研究了其对从接受冠状动脉搭桥手术的患者中采集的桡动脉（RA）、胃网膜动脉（GEA）和乳内动脉（IMA）的离体环的影响。结果表明，地塞米松对DA_1和α_1肾上腺素能受体的亲和力不同，可能是其不同的收缩和舒张作用的重要原因。3）研究了地塞米松对人阻力动脉的直接作用。从胃切除标本的网膜分离胃网膜动脉，剥脱血管内皮，测量平滑肌的力学反应。结果表明，DEX对人胃网膜动脉具有α_2-肾上腺素能激动剂和α_1-肾上腺素能拮抗剂双重作用。本文提供的数据预测，在DEX的稳态血浆水平通常低于10 μ M的正常临床条件下，DEX对血管反应性几乎没有直接影响<-7>。然而，在某些条件下，较高浓度的DEX观察到的直接α_2激动剂和α_1拮抗剂作用可显着影响血管张力。