OFF-PUMP CAB TO EVALUATE THE EFFECT OF BOTOX? ON ARTERIAL GRAFTS

Texas Biomedical Research Institute, San Antonio TX

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Abstract

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 patients 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.