This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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