ARTERIAL WALL 02 AT BIFURCATIONS AND STENOSES

脑血管疾病是美国第三大死亡原因

Cerebrovascular diseases are the third leading cause of death in the United States and are the primary cause of stroke. Arterial wall hypoxia may play a role in initiating and/or exacerbating the disease process. This research project will investigate the hypothesis that arterial wall oxygen supply is reduced after hemodynamic injury. A synergistic approach will be taken, combining histological studies, oxygen and pH microelectrode studies, and theoretical computer studies. Measurements will be obtained under well controlled conditions in vitro using isolated, perfused carotid artery and abdominal aorta segments from normal rabbits (control group 1), and from rabbits where either the carotid artery (group 2) or the abdominal aorta (group 3) has been surgically stenosed by reducing the diameter with a silk ligature. Stenoses will be made from 1 to 3 months prior to the experimental studies, allowing time for hemodynamic injury and alteration of blood vessel wall properties. Tissue oxygen consumption rates, diffusion coefficients and solubility coefficients will be estimated from oxygen microelectrode data. Lactic acid accumulation during anoxia will be estimated from tissue pH changes measured with pH microelectrodes. Measurement sites will include (a) the bifurcations downstream from the stenosis, (b) proximal and (c) distal sites. A technique for marking microelectrode tips will be used to identify the sites. Anatomical and experimental parameters will be used in computer simulations to predict how oxygen supply to the wall will change under other conditions. The microelectrode techniques and theoretical modeling developed in this research project will provide a basis for continued work on related arterial wall pathology associated with cigarette smoking, atherogenic diet, diabetes, hypertension and other risk factors. The long term objective is to provide new information which can be used to evaluate mechanisms whereby hypoxia may accelerate the atherosclerotic process, and to identify preventative interventions.