AN OFF-PUMP CORONARY ARTERY BYPASS GRAFT ANIMAL MODEL IN BABOONS

狒狒非体外循环冠状动脉搭桥动物模型

• 批准号: 8172659
• 负责人: Francisco Inacio Bastos
• 金额: $ 0.43万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172659
• 关键词: Adverse effects; Anatomy; Animal Model; Animals; Arteries; Botox; Botulinum Toxin Type A; Bypass; Cessation of life; Characteristics; Chest; Computer Retrieval of Information on Scientific Projects Database; Coronary Artery Bypass; Data; Dose; Family suidae; Fingers; Funding; Grant; Healed; Human; In Vitro; Injection of therapeutic agent; Institution; Investigation; Ischemia; Literature; Longitudinal Studies; Mediastinitis; Myocardial Infarction; Myography; Operative Surgical Procedures; Papio; Patients; Pharmaceutical Preparations; Plastics; Positioning Attribute; Preparation; Publications; Publishing; Pump; Raynaud Disease; Reporting; Research; Research Personnel; Resources; Review Literature; Sepsis; Source; Spasm; Sternum; Sudden Death; Testing; Time; United States National Institutes of Health; Wound Infection; experience; healing; human study; internal thoracic artery; operation; prevent; radial artery

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In humans, coronary artery bypass grafts (CABG) are performed using the patient's internal thoracic artery (ITA) or the radial artery (RA) for the bypass conduits. These arteries are used because of demonstrated long term patency superiority to other vessels. However during surgery and for several days or weeks after the surgery, these grafts can experience sudden severe spasm that can cause ischemia, myocardial infarction, or sudden death. Drugs are given during the surgery and afterwards to prevent the possibility of spasm but they are not long acting and require frequent repeated dosing. Additionally the drugs sometimes have serious or troublesome side effects that make them unpopular and sometimes dangerous for the patients. The ideal drug would be one that required only one application to the graft at the time of surgery, had no systemic or side effects, and lasted for weeks or months. Clostridium botulinum toxin type A (Botox) is a commercially available drug that has those favorable characteristics. Though it is commonly used in plastic and general surgery, our review of the literature reveals no published data on the specific use to block coronary bypass graft spasm. There is one report in animals that Botox reduced uterine artery spasm and a single human study in which patients with Raynaud's disease (severe spasm of the arteries to the fingers) had the spasm relieved within 5 minutes of injection with Botox. It is our additional hypothesis that Botox may be useful in CABG surgery in humans. Our first step was to perform in vitro studies to see if Botox would block vessel spasm. We just completed in vitro myography tests of multiple segments of discarded human internal thoracic artery and have shown that Botox significantly blocks the tendency for spasm when compared to controls. These results are in preparation for publication. We now need an animal model with the possibility of long term survival in order to continue our investigations. The usual animal for coronary bypass operations is porcine. However the pig is only good for short term survival studies. Its chest cage anatomy and tendency to lay on its sternum after surgery almost always results in sternal non-healing, wound infection, mediastinitis, sepsis, and early post-op death making long term studies almost impossible. We have not been able to find literature references describing coronary bypass surgery performed in the baboon; however, we postulate it would be ideal for the long term studies we need to make leading to human studies. The first step in this endeavor was to determine if the baboon's internal thoracic artery or radial artery have the size, anatomical position, and handling characteristics necessary to technically perform a bypass operation in the baboon.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在人类中，冠状动脉旁路移植术（CABG）是使用患者的胸廓内动脉（ITA）或桡动脉（RA）作为旁路导管进行的。 使用这些动脉是因为已证明其长期通畅性优于其他血管。 然而，在手术期间和手术后的几天或几周内，这些移植物可能会经历突然的严重痉挛，可能导致缺血，心肌梗死或猝死。 在手术期间和手术后给予药物以防止痉挛的可能性，但它们不是长效的，需要频繁重复给药。 此外，这些药物有时会产生严重或麻烦的副作用，使它们不受欢迎，有时对患者有危险。 理想的药物是在手术时只需要在移植物上应用一次，没有全身或副作用，并持续数周或数月。 A型肉毒梭菌毒素（Botox）是一种具有这些有利特征的市售药物。 虽然它通常用于整形外科和普外科，但我们的文献回顾显示，没有关于其具体用于阻断冠状动脉旁路移植物痉挛的已发表数据。 有一项动物研究报告称肉毒杆菌毒素可减少子宫动脉痉挛，还有一项人体研究显示，患有雷诺氏病（手指动脉严重痉挛）的患者在注射肉毒杆菌毒素后5分钟内痉挛缓解。这是我们的额外假设，肉毒杆菌毒素可能是有用的冠状动脉搭桥手术在人类。 我们的第一步是进行体外研究，看看肉毒杆菌毒素是否会阻止血管痉挛。 我们刚刚完成了对多段丢弃的人体胸廓内动脉的体外肌造影测试，并表明与对照组相比，肉毒杆菌毒素显著阻止了痉挛的趋势。 这些结果正在准备发表。 我们现在需要一种能够长期存活的动物模型，以便继续我们的研究。 冠状动脉搭桥手术的常用动物是猪。 然而，猪只适合短期生存研究。 其胸腔解剖结构和手术后躺在胸骨上的倾向几乎总是会导致胸骨不愈合、伤口感染、纵膈炎、败血症和术后早期死亡，使得长期研究几乎不可能。 我们尚未找到描述在狒狒中进行冠状动脉搭桥手术的参考文献;然而，我们假设这将是我们需要进行的长期研究的理想选择，从而导致人体研究。 这项奋进的第一步是确定狒狒的胸廓内动脉或桡动脉是否具有在狒狒中进行旁路手术所需的尺寸、解剖位置和处理特征。