Brain Vascular Studies in Cardiac and Orthopedic Surgery

心脏和骨科手术中的脑血管研究

基本信息

批准号：
8044670
负责人：
WILLIAM ROY BROWN
金额：
$ 50.79万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-04-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8044670
关键词：
Acute Address Adult Respiratory Distress Syndrome Age Air Anatomy Animal Model Animals Antibodies Area Argon Arterial Lines Attenuated Award Blood Blood - brain barrier anatomy Blood Circulation Blood Proteins Blood Vessels Blood specimen Bone Marrow Brain Brain Edema Brain Injuries Canis familiaris Cannulas Carbon Dioxide Cardiac Cardiac Surgery procedures Cardiopulmonary Bypass Carotid Arteries Celloidin Cellular Stress Cerebrospinal Fluid Cerebrovascular Circulation Cerebrum Cessation of life Chills Chronic Clinical Clinical Trials Commit Confocal Microscopy Coupled Creatine Diffusion weighted imaging Edema Embolism Encapsulated Endothelium Equipment Etiology Event Exhibits Extravasation Fatty acid glycerol esters Floods Friends Functional disorder Funding Gases Glomerular Filtration Rate Heart Heat-Shock Proteins 70 Heating Histopathology Human Hypoxia Image Analysis Imagery Imaging Techniques Incidence Infarction Inflammation Injection of therapeutic agent Injury Intervention Investigation Ischemia Kidney Knee Prosthesis Laboratories Lasers Left atrial structure Lesion Lipids Liquid substance Location Lung Magnetic Resonance Imaging Measurement Methodology Methods Modeling Neurologic Neurologic Dysfunctions Neurological outcome Operative Surgical Procedures Orthopedic Surgery procedures Orthopedic Surgical Procedures Orthopedics Outcome Partial Pressure Particulate Patent Foramen Ovale Pathology Patients Perioperative Procedures Prosthesis Proteins Publications Recovery Renal function Replacement Arthroplasty Research Research Personnel Resolution Sensitivity and Specificity Sepsis Syndrome Serum Simulate Source Staining method Stains Structure of jugular vein Study models Suction Surgeon System Techniques Testing Therapeutic Embolization Thick Thoracic cavity structure Tight Junctions Time Training Transfusion Translating Vacuum Vascular System Venous Water Weight Work bone brain tissue capillary bed cerebrovascular design experience hypoxia inducible factor 1 improved innovation neurobehavioral neuropsychological pressure prevent professor public health relevance surgical research valve replacement vascular bed

Acute Address Adult Respiratory Distress Syndrome Age Air Anatomy Animal Model Animals Antibodies Area Argon Arterial Lines Attenuated Award Blood Blood - brain barrier anatomy Blood Circulation Blood Proteins Blood Vessels Blood specimen Bone Marrow Brain Brain Edema Brain Injuries Canis familiaris Cannulas Carbon Dioxide Cardiac Cardiac Surgery procedures Cardiopulmonary Bypass Carotid Arteries Celloidin Cellular Stress Cerebrospinal Fluid Cerebrovascular Circulation Cerebrum Cessation of life Chills Chronic Clinical Clinical Trials Commit Confocal Microscopy Coupled Creatine Diffusion weighted imaging Edema Embolism Encapsulated Endothelium Equipment Etiology Event Exhibits Extravasation Fatty acid glycerol esters Floods Friends Functional disorder Funding Gases Glomerular Filtration Rate Heart Heat-Shock Proteins 70 Heating Histopathology Human Hypoxia Image Analysis Imagery Imaging Techniques Incidence Infarction Inflammation Injection of therapeutic agent Injury Intervention Investigation Ischemia Kidney Knee Prosthesis Laboratories Lasers Left atrial structure Lesion Lipids Liquid substance Location Lung Magnetic Resonance Imaging Measurement Methodology Methods Modeling Neurologic Neurologic Dysfunctions Neurological outcome Operative Surgical Procedures Orthopedic Surgery procedures Orthopedic Surgical Procedures Orthopedics Outcome Partial Pressure Particulate Patent Foramen Ovale Pathology Patients Perioperative Procedures Prosthesis Proteins Publications Recovery Renal function Replacement Arthroplasty Research Research Personnel Resolution Sensitivity and Specificity Sepsis Syndrome Serum Simulate Source Staining method Stains Structure of jugular vein Study models Suction Surgeon System Techniques Testing Therapeutic Embolization Thick Thoracic cavity structure Tight Junctions Time Training Transfusion Translating Vacuum Vascular System Venous Water Weight Work bone brain tissue capillary bed cerebrovascular design experience hypoxia inducible factor 1 improved innovation neurobehavioral neuropsychological pressure prevent professor public health relevance surgical research valve replacement vascular bed

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项目摘要

DESCRIPTION (provided by applicant): This proposal is focused on a clinically important area where we can once again have an immediate impact; preventing surgery-induced microembolic injury to the brain. Air and lipid microemboli enter the circulation during both cardiac and orthopedic surgery, causing ischemia, endothelial dysfunction, and inflammation. These emboli may occlude vessels or they can be extruded through the vascular bed and irritate the endothelium, resulting in acute and chronic neurologic, renal, and splanchnic injury. Our studies show that during cardiac surgery the major source of the lipid microemboli is from the blood salvaged from the surgical field and returned to the patient. Air emboli can come from several sources, such as from cannulae or foam in the blood. In the brain, the passage of microemboli causes blood-brain barrier (BBB) breakdown, and in other vascular beds it is associated with the systemic inflammatory response syndrome. Magnetic resonance imaging (MRI) studies reveal one out of three patients may suffer a new brain lesion following cardiac procedures. In orthopedic patients, during the pressurization of the medullary canal, fat from the bone marrow is extruded into the venous circulation. The fat embolization may cause acute respiratory distress syndrome, neurologic dysfunction, or death. We will use our dog model of cardiac surgery to study brain injury from lipid and air emboli. We will investigate air emboli introduced into the cardiopulmonary bypass (CPB) circuit in two locations, in three forms: air in the venous cannula; agitated air in water in the arterial line; and agitated air in blood (protein-coated gaseous microemboli; foam) in the arterial line. We will investigate whether air emboli can be prevented during open heart surgery by flooding the operative field with argon, a low partial pressure gas. We will also determine whether knee prosthesis surgery using a state of the art reaming system, with chilling and rinse- vacuum methodology is safer than traditional bone reaming. The outcomes will include: brain edema; intravital visualization and recording of intravascular emboli; BBB leakage into the cerebrospinal fluid; emboli count in the CPB circuit, carotid artery, and jugular vein using the EDAC. Quantifier; cerebral blood flow; stereological analysis of vascular endothelial tight junctions; quantification of brain tissue hypoxia (HIF-1); quantification of cellular stress (Hsp70); emboli counts in the brain, lungs, and kidneys; and lipid microemboli in blood samples. We will perform MRI on six groups of dogs which simulate surgical embolic events. Histological evidence will be compared to MRI studies to evaluate the MRI resolution, specificity, and sensitivity to detect the damage from emboli. The MRI analyses will include diffusion-weighted imaging (DWI), spin echo T1, and fast spin echo T2. PUBLIC HEALTH RELEVANCE: We will perform experimental cardiac and orthopedic surgeries in dogs that should provide evidence that certain surgical innovations can reduce the incidence of brain injury and even death. We expect these surgical innovations to reduce the amount of air and fat emboli that enter the bloodstream and circulate to the brain.

描述（由申请人提供）：该提案集中在一个临床上重要的领域，我们可以再次产生直接影响；防止手术引起的大脑微生物损伤。空气和脂质微栓塞在心脏和骨科手术期间进入循环，引起缺血，内皮功能障碍和炎症。这些栓塞可能会阻塞血管，或者可以通过血管床挤出并刺激内皮，从而导致急性和慢性神经系统损伤。我们的研究表明，在心脏手术期间，脂质微栓塞的主要来源来自手术领域的血液，并返回给患者。空气栓塞可能来自多个来源，例如来自插管或血液中的泡沫。在大脑中，微栓塞的通过会导致血脑屏障（BBB）崩溃，在其他血管床中，它与全身性炎症反应综合征有关。磁共振成像（MRI）研究表明，三分之二患者可能会在心脏手术后遭受新的脑病变。在骨科患者中，在髓管加压期间，骨髓中的脂肪被挤压到静脉循环中。脂肪栓塞可能会导致急性呼吸窘迫综合征，神经功能障碍或死亡。我们将使用我们的心脏手术狗模型来研究脂质和空气栓塞的脑损伤。我们将研究在两个位置的心肺旁路（CPB）电路中引入的空气栓塞，分为三种形式：静脉插管中的空气；在动脉线上的水中搅动空气；并在动脉线上搅动血液中的空气（蛋白质涂层的气态微栓塞；泡沫）。我们将通过用低压力气体的Argon淹没手术区，调查在心脏手术期间是否可以预防空气栓塞。我们还将确定使用先进的旋转系统（带冷令人震惊和冲洗）的膝关节假体手术是否比传统的骨头更安全。结果将包括：大脑水肿；血管内栓子的静脉内可视化和记录； BBB泄漏到脑脊液中；使用EDAC，在CPB电路，颈动脉和颈静脉中计数栓子计数。量词;脑血流；血管内皮紧密连接的立体分析；脑组织缺氧的定量（HIF-1）；细胞应激的定量（HSP70）； Emboli在大脑，肺和肾脏中计数；和血液样本中的脂质微栓塞。我们将对模拟手术栓塞事件的六组狗进行MRI。将组织学证据与MRI研究进行比较，以评估MRI分辨率，特异性和敏感性以检测栓子的损害。 MRI分析将包括扩散加权成像（DWI），自旋回波T1和快速自旋回波T2。公共卫生相关性：我们将对狗进行实验性心脏和骨科手术，这些手术应提供证据表明某些手术创新可以减少脑损伤甚至死亡的发生率。我们期望这些手术创新可以减少进入血液并循环到大脑的空气和脂肪栓塞量。