Dr. Bridges is engaged in a research project funded by the National Heart Lung and Blood Institute entitled: “Translational Studies in Heart Failure Gene Therapy.” We have developed new techniques to enhance vector mediated gene delivery to skeletal and cardiac myocytes. Our work involves both large animal experiments using cardiopulmonary bypass in dogs and sheep and isolated perfused rodent hearts. Our laboratory emphasizes large animal cardiac gene delivery protocols that utilize cardiopulmonary bypass to optimize gene delivery. Our platform technology is called “Molecular Cardiac Surgery With Recirculation Delivery” (MCARDTM). We were the first to use cardiopulmonary bypass coupled with cardiac isolation to dramatically enhance the efficiency of global vector-mediated gene delivery to the heart. In collaboration with Dr. Stedman’s group, we have generated intellectual property resulting in several issued and pending U.S. and foreign patents in the general field of gene delivery to striated muscle.

Most recently, we have developed a new cardiac surgical procedure (MCARDTM) and associated hardware that allows for complete isolation of the heart in situ and global myocardial gene delivery. Preliminary data derived from these experiments has demonstrated efficient global transduction of cardiac myocytes in the adult large animal heart. This approach appears to be more efficient at transducing cardiac myocytes in the adult large animal heart than any previously published approach. We have recently demonstrated improvement in myocardial mechanics in sheep after using the MCARDTM procedure to deliver therapeutic gene (?ARKct) to inhibit GRK2 in sheep. In ongoing studies we are currently translating these exciting results to deliver therapeutic transgenes in a novel ovine model of heart failure. These studies, using clinically applicable technology may ultimately lead to new treatments for heart failure and other cardiac disorders.

We are also engaged in a variety of outcomes research studies in conjunction with the Society of Thoracic Surgeons (STS) Workforce on National Databases and the STS Workforce on Evidence Based Surgery where I serve as Chairman. There is the opportunity to participate in a variety of ongoing studies including the use of aspirin in cardiac surgery, the effect of race on valve surgery outcomes, indications for aortic valve replacement, studies of patient-prosthesis mismatch in aortic valve surgery, the management of atrial arrhythmias associated with general thoracic surgical procedures and guidelines for antibiotic prophylaxis in cardiac surgery.

We work with students/faculty in the Bioengineering Department at Penn in theoretical/ mathematical investigations of cardiac mechanics with specific application to the Batista procedure and heart failure. Using both theoretical models and three dimensional imaging are working toward developing new algorithms for more accurate prediction of the probability of aortic aneurysm rupture and the rate of aneurysm growth