Project 170367

A large percentage of Canadians suffer from coronary artery disease; coronary artery bypass graft (CABG) surgery is the treatment of choice for these people. Although the intent of performing CABG is to improve coronary bloodflow, a common complication is a sudden narrowing of the transplanted artery days/weeks after surgery (caused by contraction of a muscle around the artery). Current approaches aimed at preventing this problem -- ranging from drugs to physical interventions (e.g., stents; balloons; replacement) -- are too often inadequate and only used once the problem appears. A superior method for actual prevention of this post-surgical complication is desperately needed. A novel technique which is gaining a great deal of attention in the airway/asthma field may fill this gap. In asthma, a muscle which wraps around the airway contracts, making it hard to breath. Thermoplasty involves the direct application of heat energy to that muscle, provoking little or no immediate response in the patient; however, 12 weeks later, the muscle is gone, although other important cell types are still present and look completely normal. Most importantly, the asthma has been permanently treated. We intend to explore whether thermoplasty can be used to prevent the post-surgical constriction of the implanted arteries seen in CABG through the following three experiments: Specific aim #1: examine the sensitivity of pig arteries to direct application of heat energy. Specific aim #2: address the question of whether it is possible to adapt this approach to the treatment of the donor/graft arteries immediately before grafting into the recipient. We have attached abundant preliminary data which, together with our track record, attest to our ability to complete this project. This procedure is simple, cost-effective, easily adapted to the clinical setting, with the potential to greatly reduce or even eliminate the incidence and/or severity of post-operative complications.

computational and experimental approaches to study CK2 function