Cryptic Masons Medical Research Foundation, Inc. (CMMRF) THE SUPPORT

CMMRF Funding for Indiana Center for Vascular Biology and Medicine
Updated June 3, 2003

The research that CMMRF funds falls into two basic areas: vascular remodeling and Angiogenesis.

Vascular Remodeling

Vascular remodeling basically deals with changing or reshaping the arteries and/or arterial walls to assist in the treatment of arteriosclerosis. One approach to conduct this that has been studied was the use of an arterial catheter to deliver medication to the site of an arterial blockage. However, Dr. March soon discovered that this method was relatively ineffective due to the amount of the medication that was "washed away" and carried throughout the arterial system by the blood. This led to the development of coronary sac delivery.

Coronary Sac Delivery

The heart floats in a sac of fluid and the action of beating continually bathes the heart ? in the fluid contained within the sac. Dr. March theorized that if medication were placed within this sac, then it would remain in the affected area and would not be "washed away" by normal blood flow. This method of delivery increased the effectiveness of the medication, or efficacy, substantially over that of arterial delivery, This means that less medication can be used, and the medication that is used is more effective since it stays in the affected area once delivered. The medication must work in an outside?in type of treatment where the medication bathes the exterior wall of the artery and soaks, through the vessel wall to reach the affected area. Delivery is accomplished by inserting a catheter into the chest cavity. A small apparatus at the end of the catheter then pulls a section of the sac away from the heart so a needle can penetrate the sac and deliver the prescribed medication, A number of medications and genetic treatments have been delivered in this maDner in laboratory experiments, but recently, a great deal of success has been achieved with the drug Taxol.

Taxol
Taxol is a popular cancer fighting drug whose chemical name is paclitaxel. This drug was already known to alter the cells of the body. When applied through coronary sac delivery, Taxol causes the artery to enlarge. It increases both the total circumference of the artery and the interior circumference of the lumen, or inner afterial wall. Basically, the vessel wall thickness stays fairly constant and most of the increase is seen in the interior of the artery. Taxol is a drug that is already in use. Hurnan trials v4th paclitaxel on stent coatings are currently underway.

Angiogenesis
Anglogenesis is the process of causing new arteries to grow, providing a new path around a blockage. Coronary sac delivery can be used with many drugs and genetic agents for this type of treatment. Dr. March has recently begun experimentation with a genetic agent that does not respond well to coronary sac del.ive.Ty. This agent is simply not effective in an outside?in type of delivery system and the results have caused Dr. March to investigate another method of treatment delivery.

Verious Retrograde Procedure
Dr. March still wanted to prevent the genetic agent from "washing away" so he began experimenting with temporarily blocking the artery to hold the genetic agent in the affected area. After a few experiments, he concluded it would be much safer for the patient if a vein was blocked rather than an artery, forcing the medication back through? the capillaries and arterioles (sxnall blood vessels wbich connect the arteries and the veins) and into the arteries and the target blockage. On average, the blood pressure in an artery is between 80 and 100 millimeters of mercury while the average blood pressure in a vein is between 20 and 30, or roughly one quarter to one third the pressure. An angioplasty?like balloon is used to block the vein and raise the local pressure to 200 to 300, or ten to fifteen times the normal pressure. The genetic agent is then forced backward through the system and into the affected area. The procedure is relatively new and its overall effectiveness has yet to be determined.

The Life Vest
One of the most novel paths of research being pursued is the feasibility of an apparatus that emits electromagnetic signals (radio waves) while it is worn over the heart, encouraging the arteries to grow natural bypasses around a blockage. This procedure is based on the idea that proteins have specific, dynamic frequencies at which they vibrate. If this frequency can be determined, then signals can be sent oil that frequency to encourage the cells to behave in, a particular maw?ler. This has been done successfully by bone specialists to encourage the rapid heahng of breaks , particularly in the spine and long bones of the legs. Dr. March theorized that if it would work for bones, it should work for arteries. A test apparatus has been designed and surgically implanted into a pig (the coronary system of a pig is very similar to that of a human, making it an excellent test subject for coronary research). The ability of the device to cause the pig to grow a bypass in the affected ?area is being studied. The truly difficult part of the research however, is going to be determining the frequency of the arterial wall. cells. This is a trial and er?ror process. Imagine how long it would take to scan the entire FM band on your radio if there was only one station and you had to find it with no guidelines or clues as to where it might be. Once these two major hurdles have been overcome, Dr. March hopes to realize the idea of a totally non?invasive method of treating arteriosclerosis.

The Closer
The most recent development to emerge from the laboratory supported by CMMRF is The Closer S System, an apparatus designed to assist in an angioplasty procedure. Normally during an angioplasty, a patient lies flat on his back while a catheter is inserted into the femoral artery just below the groin. The catheter then moves through the arterial system to the coronary artery system. The catheter is removed along the same path after the procedure. A nurse then applies pressure to the entry wound for 45 to 90 minutes. In the past, the patient would be required to lie flat on his back for up to 12 hours to insure that the entry wound begins to heal properly and to avoid bleeding problems. Dr. March saw that the patients found the enforced hours of immobilization unacceptable. The concept he developed is basically a surgical needle fitted to the end of a catheter. When the catheter is removed from the artery. The Closer sutures the arterial wall closed. After using The Closer, there is no need to apply pressure to the wound and the patient can get up from the table as early as several minutes after the procedure. The Closer was approved for clinical use in December 2000 and it was used on more than 500,000 patients in 2001 alone. Dr. March has pointed out that this was a larger number of patients than he would have been able to treat in his entire career as a clinical physician. The Closer took 8 years to go from an initial concept to clinical use, and it was only a minor modification to an existing procedure. Imagine the time frames we can expect for a completely new idea in coronary care to reach clinical use, such as vascular remodeling. Our research is certain to change the future of medicine, but patience will be required.

Our perseverance will be rewarded with new, life changing treatments for devastating vascular diseases. Support from the Cryptic Masons Medical Research Foundation will fuel the research that is certain to change the future of medicine.

"Our researchers are working today to develop the medicine of tomorrow." - Keith March, M.D., Ph.D. Director, IU School of Medicine ICVBM Cryptic Mason Chair in Vascular Biology and Medicine

 

                     
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