Angiogenesis

Within this experimental area, there are a number of projects which must be initially addressed to adequately establish a foundation for research studies and clinical applications.

Developing methods to initiate new arterial blood inflow
These ongoing studies were started by using growth factors in association with coronary artery bypass grafts into areas of the heart rendered ischemic by placing an occlusive device around a coronary artery and waiting 3 weeks for an ischemic area of the heart to develop. The bypass graft was placed into the ischemic muscle with growth factors injected around the graft. Evaluation of the area was carried out after 3-4 weeks of recovery. Histological evaluation, blood flow changes, fluoroscopy, and echocardiography evaluation were used to determine the efficacy of the procedures.

Utilization of new growth factors
Through the various methods of genetic engineering, we will be able to isolate, clone and concentrate new growth factors and enhance the activity of the presently available factors. In this way, we will be able to tailor the activity with other ischemic cell products to maximally utilize the growth stimulus for new arterial growth.

Combination of growth factors
There are quite a few compounds being tested to enhance new arterial growth in various tissues including cardiac muscle. Very little has been done to examine the efficacy of combining different growth factors and to examine the efficacy of combining different growth factors and to determine the possible synergistic effect of these techniques. Also, certain metabolic byproducts are generated in ischemic muscles that may provide a stimulatory response to enhance growth factor effectiveness.

Delivery methods for cellular placement of growth factors
One of the major problems in the area of angiogenesis is not only isolating the growth factors, but delivering them to ischemic tissue and having them stay in place until a response is generated. Various methods are being tested which include a viral vector in which the growth factor is placed within a noninfective virus and injected into the ischemic tissue. Another avenue that we would like to pursue, is the use of biodegradable beads onto which growth factor has been attached. These beads would be placed into the muscle either by surgery or a catheter delivery method. The slow release of the growth factor from these beads is necessary to maintain an environment conducive to stimulating arterial growth. Development of these beads will be necessary for clinical use after FDA approval.

Enhancing the positive outlook for the "non-surgical" cardiac patient
The technique to grow new arteries will greatly change the future of the "cardiac patient" that has undergone the whole gamut of corrective techniques and still has not received relief from the symptoms of chest pain, shortness of breath and the ability to enjoy physical activity. By stimulating new arterial growth, these patients will be "cured" and not just temporarily patched and mended while the disease process of atherosclerosis continues. The ultimate application of this technique may eliminate the need for certain types of cardiac surgery.