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: 2028810
• 负责人: BRUCE J LEONE
• 金额: $ 8.31万
• 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 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2028810
• 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.

这个项目将检验血液稀释、输血的效果 治疗，与人重组血红蛋白对全球和局部心脏的影响 大鼠实验性冠脉病变时的心肌功能 动脉狭窄。我们将检验血液稀释这一中心假设 对缺血右心室的影响有显著差异 与缺血的左心室相比。实验室的两种模式 使用犬类制剂的冠状动脉狭窄将被采用：关键 左冠状动脉前降支狭窄，重度右冠状动脉狭窄 冠状动脉狭窄。将检查全球血流动力学功能 (体、肺和脑室压力、心输出量、时间 左、右室等容松弛常数(Tau) 左、右室压对时间的导数 [LV dP.dt和RV dP.dt]，冠脉血流)； 心肌功能声学测量)将被用来表征 右翼不同区域(正常和流动受损)的反应 从左心室到血液稀释。血液稀释对权利的影响 左心功能将在一系列实验中描述 旨在阐明1)全球血流动力学和 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)耐受流量 随着时间的推移，对血液稀释诱导的轻度缺血的损害心肌； 3)急性血液稀释耐受性：重组人的影响 血红蛋白；4)逆转缺血，输血治疗 血液稀释诱导的缺血，并与血液稀释以逆转血流 严重的脑缺血。关于容忍权利和权利的特征 左心室，局部血流正常和受损，至轻度 和严重的血液稀释，并描绘出是否适合 预防或减轻血液稀释引起的输血治疗 缺血，可能导致同种异体输血减少。 携带氧气的血液替代品的血液替代疗法 长期以来一直在寻求，特别是在患者的液体补充治疗方面 患有冠状动脉疾病。人类重组血红蛋白是一种新的， 具有物理特性的基因工程血红蛋白类似物 与葡聚糖相似，但能够将氧气输送到外周 组织，因此可能具有显著的优势 常规液体疗法在冠状动脉功能不全中的应用。我们 将检测和比较人类重组血红蛋白和 右旋糖苷在左、右室缺血模型中的应用 遗传性血液置换治疗的潜在益处 经过改造的人造血液。