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双阿司匹林交联血红蛋白(DCLHb)对大鼠全身血流动力学和局部血液循环的剂量反应效应。

Dose response effect of diaspirin crosslinked hemoglobin (DCLHb) on systemic hemodynamics and regional blood circulation in rats.

作者信息

Barve A, Sen A P, Saxena P R, Gulati A

机构信息

Department of Pharmaceutics & Pharmacodynamics, University of Illinois at Chicago 60612, USA.

出版信息

Artif Cells Blood Substit Immobil Biotechnol. 1997 Jan-Mar;25(1-2):75-84. doi: 10.3109/10731199709118899.

DOI:10.3109/10731199709118899
PMID:9083628
Abstract

Diaspirin crosslinked hemoglobin (DCLHb, Baxter Healthcare Corporation) a hemoglobin-based blood substitute has been found to increase mean arterial pressure (MAP) in a dose limiting manner. The present study was undertaken to determine dose-dependent effects of DCLHb on systemic hemodynamics and regional blood circulation. DCLHb (10% solution) in doses of 133, 400 and 1200 mg/kg i.v. was given to urethane anaesthetized rats. Normal saline (12 ml/kg) served as a control. Cardiovascular parameters were determined using a radioactive microsphere technique. DCLHb in the doses of 133, 400 and 1200 mg/kg i.v. produced a 46%, 67% and 65% increase in MAP, respectively. Total peripheral resistance (TPR) increased significantly with 133 and 400 mg/kg dose, while cardiac output increased significantly with 400 and 1200 mg/kg dose. There was no change in heart rate. A dose of 133 mg/kg of DCLHb produced a significant decrease in blood flow to the musculoskeletal system, kidney and liver. DCLHb in the dose of 400 and 1200 mg/kg significantly increased blood flow to the heart, gastrointestinal tract (GIT), mesentery & pancreas and skin. All doses of DCLHb produced a significant increase in vascular resistance to the musculoskeletal system and liver. DCLHb in the dose of 133 mg/kg increased resistance to the GIT. heart, skin and kidneys, while the dose of 400 mg/kg increased resistance to the kidneys. A dose of 1200 mg/kg decreased coronary vascular resistance. It is concluded that cardiovascular effects appear to be different with higher (1200 mg/kg) and lower (133 mg/kg) doses of DCLHb.

摘要

双阿司匹林交联血红蛋白(DCLHb,百特医疗保健公司生产)是一种基于血红蛋白的血液替代品,已被发现会以剂量限制的方式升高平均动脉压(MAP)。本研究旨在确定DCLHb对全身血流动力学和局部血液循环的剂量依赖性影响。将10%溶液形式的DCLHb以133、400和1200mg/kg静脉注射给氨基甲酸乙酯麻醉的大鼠。生理盐水(12ml/kg)作为对照。使用放射性微球技术测定心血管参数。静脉注射133、400和1200mg/kg剂量的DCLHb分别使MAP升高46%、67%和65%。133和400mg/kg剂量时总外周阻力(TPR)显著升高,而400和1200mg/kg剂量时心输出量显著增加。心率无变化。133mg/kg剂量的DCLHb使肌肉骨骼系统、肾脏和肝脏的血流量显著减少。400和1200mg/kg剂量的DCLHb使心脏、胃肠道(GIT)、肠系膜和胰腺以及皮肤的血流量显著增加。所有剂量的DCLHb均使肌肉骨骼系统和肝脏的血管阻力显著增加。133mg/kg剂量的DCLHb增加了对GIT、心脏、皮肤和肾脏的阻力,而400mg/kg剂量增加了对肾脏的阻力。1200mg/kg剂量降低了冠状动脉血管阻力。结论是,较高(1200mg/kg)和较低(133mg/kg)剂量的DCLHb的心血管效应似乎有所不同。

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