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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在人类，冠状动脉搭桥术(CABG)是使用患者的胸内动脉(ITA)或桡动脉(RA)作为搭桥管道。使用这些动脉是因为与其他血管相比，这些动脉显示出长期的通畅性优势。然而，在手术期间以及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，可能会导致缺血、心肌梗死或猝死。手术期间和手术后都会给药，以防止痉挛的可能性，但它们的作用时间不长，需要频繁重复服药。此外，这些药物有时会有严重或麻烦的副作用，使它们不受欢迎，有时对患者来说是危险的。理想的药物应该是在手术时只需对移植物进行一次应用，没有全身或副作用，并且持续数周或数月。 A型肉毒梭菌毒素(Botox)是一种具有这些有利特性的商业化药物。虽然它通常用于整形和普通外科手术，但我们对文献的回顾显示，没有公开的数据表明它可以阻断冠状动脉旁路移植的痉挛。有一份动物研究报告表明，肉毒杆菌可以减少子宫动脉痉挛，而在一项单一的人类研究中，雷诺氏病(严重的手指动脉痉挛)患者在注射肉毒杆菌后5分钟内痉挛缓解。这是我们的附加假设，即肉毒杆菌毒素可能在人类冠脉搭桥术中有用。 我们的第一步是进行体外研究，看看肉毒杆菌是否能阻止血管痉挛。我们刚刚完成了对多段废弃的人胸内动脉的体外肌电图测试，结果表明，与对照组相比，肉毒杆菌显著阻止了痉挛的倾向。这些结果正在为出版做准备。 我们现在需要一个具有长期存活可能性的动物模型来继续我们的研究。进行冠状动脉搭桥手术的动物通常是猪。然而，猪只适用于短期的生存研究。它的胸腔解剖结构和术后倾向于躺在胸骨上，几乎总是导致胸骨无法愈合、伤口感染、纵隔炎、脓毒症和术后早期死亡，使得长期研究几乎是不可能的。我们还找不到文献资料描述在狒狒身上进行的冠状动脉搭桥手术；然而，我们认为这将是我们需要进行的长期研究的理想选择，从而导致人类研究。 这项工作的第一步是确定狒狒的胸内动脉或放射状动脉是否具有从技术上为狒狒执行搭桥手术所需的大小、解剖位置和操作特性。

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.