Angioplasty

The heart, like any other muscle in the body, needs a steady supply of oxygen-rich blood. If the coronary arteries are partially blocked, the blood flow will be greatly reduced, resulting in chest pain or a heart attack. Up until recently, if chest pain could not be controlled by medication, open heart surgery was the only alternative. Research on rabbits, dogs and other animals has led to the development of a new procedure to open blocked coronary arteries.

This procedure, called angioplasty, is now in common use among cardiovascular specialists. It takes only a few hours to complete and does not require the administration of general anaesthesia.

In angioplasty, a thin tube, or catheter, is inserted into a large artery in the arm or groin and advanced up the aorta toward the heart. From there, it is carefully threaded into the narrowed coronary artery. The tip of the tube is equipped with a tiny balloon, which opens the blockage when inflated.

Cardiac catheterization is used prior to this procedure to determine exactly where the arteries are blocked. Blood vessels are filled with a dye so that the blockage can be seen. Often the angioplasty procedure itself can directly follow cardiac catheterization, requiring only a few hours of the patient's time, and the entire procedure generally has about a 3-day recovery period. This short time frame for the procedure and recovery makes angioplasty a tremendous advance over open heart surgery.

Cardiac Surgery

The function of the heart is to keep oxygen-rich blood circulating through the body. The cells of the body need a steady supply of oxygen, particularly those in the brain. To serve this purpose, the heart acts as a pump, divided into four chambers which are connected by tiny flaps of tissue called valves.

The chambers of the heart work together to keep blood circulating. At the end of each cycle, veins return the blood to the right atrium, the first of the four chambers. The oxygen in this blood has been depleted and the blood must be delivered to the lungs, where carbon dioxide is exchanged for oxygen. From the right atrium, the blood flows through the tricuspid valve and into the second chamber, the right ventricle. The right ventricle contracts when it is filled, pushing the blood through the pulmonary artery which leads to the lungs.

From the lungs, the blood travels through the pulmonary veins to the third chamber, the left atrium. When the left atrium is filled, it forces the blood through the mitral valve to the left ventricle. From there, it is pushed into a major blood vessel, called the aorta, for distribution throughout the body.

The contractions of these four chambers are co-coordinated by electrical impulses from a tissue called the pacemaker, which is located in the right atrium. Normally, about 70 signals are sent out from the pacemaker each minute, making the heart's chambers contract in the proper sequence.

Since the heart is made of muscle, it must have its own blood supply, which is provided by the coronary arteries. Heart disease can result from damage to the heart muscle, the valves, the pacemaker or the coronary arteries. If the muscle is damaged, the heart is unable to pump properly. If the valves are damaged, blood cannot flow normally from one chamber to the next. If the coronary arteries are damaged, the heart muscle does not receive proper nourishment from the blood. If the conducting system, or some muscle area, is damaged, the pattern of muscle activation is altered. In severe cases this can lead to poor pump activity or death.

Transplantation: The Gift of Life

Transplantation of organs is one of the miracles of twentieth century medicine. Viewed as impossible in the 1950s, organ transplants have become today's life-giving therapy.

The aim of transplantation research is to have the immune system accept the presence of the transplanted organ, while retaining the ability to fight infection.

Stepping Stones to Successful Transplantation in the 20^th Century:

• Alexis Carrell received the Nobel Prize in 1912 "in recognition of his work on vascular structure and the transplantation of blood vessels and organs." He was the first to demonstrate that animals tolerated grafts from their own tissues (autographs), but rejected those from unrelated animals.
• Medawar studied the rejection of skin grafts between strains of mice. He learned that successive attempts to graft skin from unrelated mice result in even more rapid rejection.
• Graft rejection can be prevented in mice and chickens if foreign cells from the future donor are introduced into the recipient when it is immunologically immature (i.e., in fetal or neonatal life). A skin graft would, for instance, survive if transplanted to an unborn mouse, but fail if given to an adult mouse (Medawar, MacFarlane, Burnet).
• Skin grafts between non-identical twin calves are not rejected because the calves share a common blood circulation in utero and are exposed to each other's blood cells before birth.
• MacFarlane, Burnet and Fenner (1949) deduced from experiments on animals that the body can distinguish "self" from "non-self." For this they received the Nobel Prize in 1960.
• Billingham and Medawar (1951) showed that corticosteroid hormones from the adrenal grand can delay skin graft rejection in animals such as rabbits. Dempster showed that steroids could ameliorate rejection of kidney transplants in dogs ("rescue therapy"). Thus it was shown that the previously-assumed insurmountable barrier to transplantation could be overcome. This knowledge was used to extend the useful duration of skin allografts in badly burned children, and also led to the recognition of graft-versus-host disease.

Advances in Surgical Aspects of Transplantation:

• Surgical techniques for transplantation of kidneys were developed in dogs. Subsequent techniques were developed for transplantation of livers, hearts and lungs.
• Bone marrow transplantation was studied in rabbits, mice and dogs.
• The science of cryobiology (freezing) made possible the storage, first of rabbit skin, then of organs in general, for months at -79^o C.
• Barnard and his team practiced surgical techniques for three years on cadavers and anaesthetized live animals before they did the first human heart transplant in 1967.
• Lower and Shumway worked for many years on dogs to improve cardiac surgical techniques. Despite their technically-excellent surgery, human transplants failed because they could not control the rejection reaction. Shumway achieved permanent success in 1970.
• Thomas performed the first successful human bone marrow transplant in 1956.
• Murray and colleagues proved that kidney transplantation was possible. Caine showed that the drug Amarine (azathioprine) could prevent kidney transplant rejection in dogs. Murray and Thomas were awarded the Nobel Prize (1990) for their groundwork studies. This work was done largely on dogs. The Nobel citation said that the discoveries were "crucial for those tens of thousands of severely ill patients who can either be cured or given a decent life when other treatments are without success."

Facing the Rejection Problem:

• Borel in Switzerland isolated cyclosporine from a fungus he found in Norway (1977). White in England found that cyclosporine much improved the acceptance of transplanted hearts in rats and pigs, and kidney transplants in dogs.
• Tissue typing for good matching of donor organ and recipient developed as immunological knowledge grew (histocompatibility and cytotoxic cross-matching). Snell pioneered studies of transplantation genetics in mice to identify the antigenic differences among strains of mice.
• International registries were established to enable rapid access to appropriate organs as they became available.
• The structure and function of the major histocompatibility complex genes was deduced by Dausset, Snell, and Benacerraf. Animals such as mice and rabbits were crucial for this work. These researchers were awarded the Nobel Prize in 1980.
• The recognition that there are numerous types of lymphocytes was made possible by the discovery of monoclonal antibodies. These antibodies are formed by fusing cancer cells with spleen cells of an experimental animal. These antibodies are the basis of one of the most effective forms of therapy for the rapid reversal of transplant rejection. Kohler and Milstein were awarded the 1984 Nobel Prize for their discovery of monoclonal antibodies.
• Since then, surgical techniques, medical management and new drugs (all tested on animals), as well as various drug combinations, have allowed successful single and double lung transplants, liver, kidney and pancreas transplants, multiple organ transplants, and small bowel transplants.

The Need:

Many terminally ill uremic patients are young and otherwise healthy. Many young people suffer from cystic fibrosis and need double lung transplants. For those lucky enough to receive organ transplants, a return to a completely healthy state and normal life is achieved in 80 percent of kidney and heart transplants; 70 percent of liver transplants; and 90 percent or corneal transplants.

However, there is a shortage of organs for transplantation. As fewer appropriate organs become available (due to less drunken driving, seat belts, and better medical and surgical treatments of trauma), waiting lists for organs become longer and longer. Every year in Canada there are thousands of people on waiting lists for organ donations; only about 40 per cent of those waiting are able to receive organ transplants.

The Next Step - Xenotransplantation:

The logical next step is cross-species transplantation. New knowledge and new drugs to enable effective control of tissue rejection open up the possibility that organs transplanted between closely-related species could function normally. Although optimal anti-rejection drug protocol is not yet known, research holds the hope that sometime in the future, patients who would die because a human organ is not available might be successfully transplanted.

For more information on transplantation choose one of the links below:

Bone Marrow

Cornea

Heart

Kidney

Liver

Lung

Skin

Other