April 1996
Media Contact: John Cramer
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Challenge: Saving Heart Without Brain Risk

Saving the heart can endanger the brain, but animal research by Johns Hopkins scientists may have taken a step toward reducing the risk.

During open-heart surgery, a heart-lung bypass machine is routinely used to maintain a patient's oxygen supply while the heart is stopped. But in some difficult types of heart surgery, deep hypothermia, or dropping a patient's body temperature to an especially low level, is often used instead of a bypass machine. The cold slows the metabolism of tissues, reducing the need for oxygen and giving surgeons more time to operate on the large arteries and veins around the heart. But stopping the heart without a bypass machine is linked to a high rate of brain damage. Most patients can survive in this state of suspended deep-cold animation for 60 minutes before irreversible brain damage begins, but the damage begins earlier in other patients.

Working with dogs, Hopkins researchers tested whether the brain's increased production of the chemical nitric oxide damages nerve cells after the heart is stopped in deep hypothermia. Nitric oxide is considered one of nature's Swiss-army knives, an all-purpose molecule with a key role in transmitting messages between nerve cells, regulating blood pressure and destroying foreign invaders. Organisms from humans to slime molds naturally produce it.

The investigators stopped the hearts of 17 dogs for two hours using only deep hypothermia, and found that soon afterward the level of nitric oxide had increased in the nerve cells in the brains and cerebrospinal fluid.

"This suggests that stopping the heart without using a heart-lung bypass machine may cause an early and significant build-up of nitric oxide in the brain and that this is what's damaging the nerve cells," says Malcolm Brock, M.D., a surgery fellow and lead author of the study. "Now we can develop strategies to block the action." The study was presented at the Society of Thoracic Surgeons' annual meeting recently.

Paralysis Link to Blood Vessel Surgery Studied

Paralysis after surgery to repair the body's main blood vessel may be caused by a build-up of natural substances that damage the spinal cord, according to a Johns Hopkins study. The results suggest a link between paralysis and prolonged stoppage of blood flow through the aorta, and provide insight that may be used eventually to prevent the problem.

"Stopping the blood flow through the aorta for too long may create a buildup of neurotransmitters that overstimulate the spinal cord, triggering a cascade of chemical reactions that kill the nerve cells and cause paralysis," says Malcolm Brock, M.D., a surgery fellow and lead author of the study.

Hopkins scientists studied 16 patients who underwent surgery to repair aneurysms -- weakened or torn areas -- in the large blood vessels in the chest and abdomen, including the aorta. Without the surgery, patients may die. The patients' cerebrospinal fluid was measured during and after surgery for excitatory amino acids -- building blocks that make up the body's proteins and stimulate production of chemical messengers between nerve cells. The four patients who developed paralysis were found to have significantly higher levels of these amino acids than the 12 patients who had no paralysis.

The study found that the amino acid levels were especially high when the aorta was clamped to stop the blood flow and again 15 hours after surgery. The study was presented recently at the Society of Thoracic Surgeons' annual meeting.

Pigs May Add Another Chapter In Heart Research

Pigs, whose hearts have long proved invaluable to medical research, may have contributed to another finding in the fight against heart disease in people.

Johns Hopkins scientists are studying ways to stimulate cells to form and grow blood vessels in people with end-stage heart disease, which occurs when not enough oxygenated blood reaches the heart. Restoring the blood supply can reduce the symptoms and extend patients' lives. The structure of pigs' hearts is similar to human hearts.

The Hopkins team used lasers to cut tiny channels into pigs' heart muscle and observed increases in the formation of blood vessels supplying those muscles. After creating the channels, researchers analyzed the changes in the heart tissue. A month after the laser treatment, the channels had closed with scar tissue, but the results suggest that the channels allowed blood to pour directly through the heart muscle.

The scientists cautioned that the increased blood supply simply may have been the damaged tissue's general response to an injury and not a specific change in the tissue's molecular makeup that would cause new blood vessels to form and grow, says Kirk Fleischer, M.D., the study's lead author and a surgery fellow.

"This finding adds to our knowledge, but more study is needed to demonstrate existence of a true response that forms and grows blood vessels in heart tissue," says Fleischer, who presented the results at the Society of Thoracic Surgeons' annual meeting recently.

-- JHMI --
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