Brain damage that occurs during certain heart surgeries may be reduced by stopping a natural chemical from overstimulating brain nerve cells to the point of self-destruction, a Johns Hopkins animal study suggests.
Scientists, who likened the process to a gatekeeper blocking flood waters from breeching the cell walls and triggering cellular "suicide," will present their results Oct. 8 at the American College of Surgeons' annual meeting in San Francisco.
"Our results provide the first evidence that a toxic overload of the chemical glutamate plays a role in the development of programmed brain cell death when the heart is stopped during hypothermia, and indicate that blocking glutamate receptors on the cell surface reduces this kind of cell death," says Elaine E. Tseng, M.D., the study's lead author and a surgery fellow.
Brain damage sometimes occurs during cardiac surgery when the heart is stopped for a long period using hypothermia, or greatly lowering the patient's body temperature to reduce the need for oxygen and then draining the blood from the body. Some of the damage occurs through apoptosis, a form of programmed cell death in which the brain cells follow built-in instructions to kill themselves.
Hopkins scientists performed cardiac pulmonary bypass surgery on 12 dogs placed on hypothermic circulatory arrest for two hours to learn what triggers brain cell apoptosis in these circumstances and how to combat it. Six dogs received a drug, called MK-801, to determine if it would block glutamate from overexciting brain cells and starting apoptosis. Glutamate is a neurotransmitter, that transmits messages between brain nerve cells and acts as a stimulant throughout the central nervous system.
Results show the dogs receiving the drug had significantly fewer brain cells undergo apoptosis than the other dogs. The drug works by binding to glutamate receptors on the surface of brain cells before the glutamate can, thus blocking too much of the chemical from entering. In both groups of dogs, apoptosis began eight hours after hypothermic circulatory arrest, while necrosis (cell death by swelling and disintegration) appeared at 72 hours, but the cell damage was less severe in the dogs receiving the drug, the results show.
The study's other authors were Malcolm V. Brock, M.D., Molly S. Lange, Mary E. Blue, Ph.D., Charles J. Lowenstein, M.D., Juan C. Troncoso, M.D., Michael V. Johnston, M.D. and William A. Baumgartner, M.D.