5. atherosclerosis or arteriosclerosis
Atherosclerosis develops in various arteries in whole body. Diabetes mellitus (blood sugar level becomes too high and kidney, eyes, heart, arteries, and nerves are diseased), hyperlipidemia (blood cholesterol or triglyceride is too much)、hypertension, smoking, obesity, stress, chronic renal failure/hemodialysis, metabolic syndrom, aging, and other various factors can cause atherosclerosis. Controlling healthy style of life such as proper dieting and exercise, punctual activity is important. Those patients who think the above things not being done are recommended to consult the family doctor or general physician. We also recommend regular check-up.
As a specialist of cardiovascular surgery, I explain about atherosclerosis from the viewpoint.
Q: What kind of treatment are there for atherosclerosis of heart?
means mainly coronary artery disease. Please see the pages of "ischemic heart disease (coronary artery disease)" in this home page. Left figure shows a typical case of coronary bypass grafting surgery (CABG).
Internal thoracic artery (ITA, previously named internal mammary artery) has a remarkable merit of resistance to artherosclerosis, and is the best graft material for CABG surgery.
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Q: What type of atherosclerosis are there for Aorta?
A: For aortic atherosclerosis please see the pages of aortic disease in this home page. Aortic atherosclerosis includes Aortic aneurysm where Aorta dilate to something like a bag or big pipe, and in a wide sense, Aortic dissection where the Aortic wall detach into 2 layers (inner layer and outer one).
Q: Atherosclerosis of legs can cause necrosis, right?
A: Atherosclerosis of legs, especially ASO (arteriosclerosis obliterans) is now a big problem of whole society. Those who have diabetes mellitus or chronic renal failure/hemodialysis often have the ASO.
Burger's disease which usually bothers young patients has a different cause of the disease from ASO, but it has leg ischemia (i.e., shortness of blood supply) which seems similar to ASO. When the arteries of legs become narrowed and finally occluded, the leg become necrotic (figure), which causes not only pain but also death. In the situation, the necrotic leg should be amputated, in order to save the patient's life.
According to some report, in Japan over 10 thousand people have their legs amputated because of the disease. After the amputation, the patient's life may be saved, but at the sacrifice of his/her quality of life. Those who have a job may lose it. Senile patients can no longer look after himself/herself and the lack of exercise can make general condition worse.
Recently cholesterol emboli which is related to catheter intervention is increasing. Cholesterol emboli occlude the leg arteries, causing severe pain and necrosis of the leg, often necessitate amputation.
If you have your leg, foot or toe fingers become cold, or blue colored, early consultation to the specialist is recommended. If you do not know the specialist of leg ischemia, you can consult cardiologist or general physician or vascular specialist.
Q: What kind of treatment is there if ASO of leg gets worse?
When a large-size artery of the leg becomes narrowed due to atherosclerosis, catheter intervention (PTA) can help recover the blood flow to the leg. Condition of the leg can improve. When catheter intervention is not feasible, bypass surgery can help improve the ischemic leg; the bypass surgery includes aorto-femoral bypass, femoro-popliteal bypass or even more distal bypass surgery.
When the bypass surgery is not feasible, or when the bypass does not have enough blood flow, other strategy will be necessary. For example, some drug can make the blood easier to flow, some other can make the blood cell flexible and make it easier to go though narrow vessels, and some drug infusion can dilate the narrowed arteries and improve the condition of the ischemic leg.
Q: When the conventional treatment fails, is there any other method to cure the leg?
When the conventional treatment as described above does not restore blood supply to leg and when the leg is on the verge of amputation, new treatment named angiogenesis may be an answer. Angiogenesis is a regenerative medicine or tissue engineering.
Left figure shows the effects of slow release of bFGF for ishcemic leg in an animal experimental study.
bFGF is a natural protein in human or animals and can make new vessels especially arteries.
After the treatment of bFGF slow release, a lot of visible vessels are made.
We did similar experimental studies using rats with diabetes mellitus or high cholesterol. After confirming safety and effectiveness, we started clinical trial as described below.
In the field of regenerative medicine, transplant of bone marrow cells especially mononuclear cells to the ischemic leg is a known method. We developed new method to further improve the results. We employ 4-week sustained release method which had been developed by Professor Yasuhiko Tabata at Institute of Frontier Medicine in Kyoto University. We did bFGF sustained release for 7 patients with leg ischemia. In most patients the leg pain dissappeared or improved, and leg skin ulcer healed. Being encouraged by the results, we are preparing another clinical trial in an Asian country, since the trial in Kyoto University Hospital is now stopped. We put priority to safety and are preparing the new clinical trial especially from the legal and ethical viewpoints.
The picture compares the leg before and after the treatment of bFGF slow release in a patient with Burger's disease. The method has similar resutls in patient with ASO.
Since the clinical trial (Phase I-II) is to confirm the safety, we used minimum amount of bFGF. Thus, when we use full dose of bFGF, even better results are expected.
In the future, omnipotent cell such as ES cell and iPS cell may be promising. At the moment, they remain experimental, and effects or safety are unknown. Thus we study bFGF which is a natural protein and has less concern of the problems.
Q: How is the regenerative medicine using bFGF?
Slow release of bFGF protein has several merits:
１．The method is not a gene therapy and does not use vector. Thus there is no concern of future disease such as cancer development.
２．bFGF remains in the injection site (i.e., leg), and does not go to other part of the body. Blood level of bFGF after the treatment is just the same as healthy people. Thus, there is eventually no concern of effects or side effects of bFGF in other part of the body.
３．The method does not use drugs (e.g. G-CSF) that pushes cells out of bone marrow, and thus no concern of the influence of the drug.
Moreover, bFGF can create small arteries which can carry more blood than capillaries. Bone marrow mononuclear cell are reported to create mainly capillaries. Arteries can last longer than capillaries.
Microscopic photo (above) shows that slow release of bFGF made more large-bore vessels than mononuclear cells.
４．The method needs only intramuscular injection and it can be completed in 15 minutes. It is minimally invasive.
In the future, the method will be done in out-patient department, but for now, we do it under lumbar anesthesia in the operating room to take a safer side.
