HEMODILUTION, ARTIFICIAL BLOOD EFFECTS ON HEART FUNCTION

血液稀释、人工血液对心脏功能的影响

• 批准号: 2225378
• 负责人: BRUCE J LEONE
• 金额: $ 9.68万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2225378
• 关键词: artery stenosis; blood /plasma substitute; blood cell count; blood volume; coronary artery; dextrans; dogs; heart function; heart ventricle; hemodynamics; hemoglobin; myocardial ischemia /hypoxia; recombinant proteins

This project will examine the effects of hemodilution, transfusion therapy, and human recombinant hemoglobin on global cardiac and regional myocardial function in the setting of significant experimental coronary artery stenosis. We will test the central hypothesis that hemodilution has significantly different effects on the ischemic right ventricle as compared to the ischemic left ventricle. Two models of laboratory coronary stenosis using a canine preparation will be employed: critical left anterior descending coronary artery stenosis, and critical right coronary artery stenosis. Global hemodynamic function will be examined (systemic, pulmonary and ventricular pressures, cardiac output, time constant of isovolemic left and right ventricular relaxation (tau), first derivative of left and right ventricular pressures with respect to time [LV dP.dt and RV dP.dt, respectively], coronary blood flow); regional myocardial function sonomicrometry) will be used to characterize the response of different regions (normal and flow-compromised) of the right and left ventricle to hemodilution. The effects of hemodilution on right and left ventricle function will be described in a series of experiments designed to elucidate 1) Characterization of the global hemodynamic and regional function response of flow compromised myocardium to hemodilution: tolerable hematocrit range; 2) Tolerance of flow compromised myocardium to hemodilution - induced mild ischemia over time; 3) Tolerance to acute hemodilution: effects of human recombinant hemoglobin; 4) Reversal of ischemia, with transfusion therapy for hemodilution-induced ischemia, and with hemodilution to reverse flow compromised ischemia. Characterization of the tolerance of the right and left ventricles, with normal and compromised regional blood flow, to mild and severe hemodilution, and delineation of the appropriateness of transfusion therapy to prevent or alleviate hemodilution-induced ischemia, may result in decreased homologous blood transfusions. Blood replacement therapy with an oxygen-carrying blood substitute has been long sought, particularly in fluid replacement therapy for patient with coronary artery disease. Human recombinant hemoglobin is a new, genetically engineered hemoglobin analog which has physical properties similar to Dextran, yet is capable of oxygen delivery to peripheral tissues, and thus may have significant advantages as compared to conventional fluid therapy in the setting of coronary insufficiency. We will examine and compare the effects of human recombinant hemoglobin with Dextran in models of left and right ventricular ischemia to assess the potential benefit of blood replacement therapy with genetically engineered artificial blood.

本项目将研究血液稀释、输血 治疗和人重组血红蛋白对整体心脏和局部 在显著实验性冠状动脉病变的情况下的心肌功能 动脉狭窄 我们将检验血液稀释 对缺血性右心室有显著不同的影响， 与缺血性左心室相比。 两种实验室模式 将使用犬制备的冠状动脉狭窄：关键 左冠状动脉前降支狭窄，右冠状动脉严重狭窄 冠脉狭窄 将检查总体血流动力学功能 （全身、肺和心室压力、心输出量、时间 等容左室和右室舒张常数（tau），第一 左心室和右心室压力对时间的导数 [LV分别为dP.dt和RV dP.dt]，冠状动脉血流量）;局部 心肌功能声显微测量）将用于表征 右侧不同区域（正常和血流受损）的反应 左心室血液稀释 血液稀释对右心室功能的影响 和左心室功能将在一系列实验中描述 旨在阐明1）总体血流动力学的表征， 血流受损心肌的局部功能反应 血液稀释：可耐受的红细胞压积范围; 2）流量耐受性 随着时间的推移，血液稀释诱导的轻度缺血损害心肌; 3)急性血液稀释的耐受性：人重组 血红蛋白; 4）缺血恢复，输血治疗 血液稀释诱导的缺血，以及用血液稀释逆转血流 局部缺血 对人权和基本自由的容忍的特点 左心室，局部血流正常和受损，至轻度 和严重的血液稀释，并描述适当的 预防或减轻血液稀释诱导的输血治疗 缺血，可能导致减少同源输血。 使用携氧血液替代品的血液替代疗法 长期以来一直在寻求，特别是在用于患者的液体替代疗法中 冠状动脉疾病 人重组血红蛋白是一种新的， 具有物理性质的基因工程血红蛋白类似物 类似于右旋糖酐，但能够将氧气输送到外周 组织，并且因此与 在冠状动脉功能不全的情况下进行常规液体治疗。 我们 将检查和比较人类重组血红蛋白与 右旋糖酐在左心室和右心室缺血模型中的作用， 血液替代疗法的潜在益处 人造血液