Cooling the body for heart surgery causes an overproduction of the neurotransmitter glutamate, an excitatory amino acid, and can leave the nervous system vulnerable to damage from the start of the cooling process until up to eight hours after recovery, a Johns Hopkins animal study suggests. This contradicts previous theories that brain damage occurred only during the initial recovery period.
Results of the study, supported by the National Institutes of Health and the Nina Braunwald Research Fellowship from the Thoracic Surgery Foundation for Research and Education, will be presented Oct. 14 at the American College of Surgeons' annual meeting in Chicago.
During the cooling process, called hypothermic circulatory arrest (HCA), the body temperature is lowered to reduce the need for oxygen, the heart is stopped and a heart-lung bypass machine takes over circulation in an effort to prevent brain damage. Prolonged HCA, however, may increase the risk of brain damage, leading to problems in learning, memory and involuntary movements.
The researchers measured brain levels of the potentially toxic amino acids glutamate, glycine and citrulline (a marker of nitric oxide) in a group of dogs during closed-chest cardiopulmonary bypass and two hours of HCA. Significant increases in glutamate were observed throughout the cooling process, recovery period and up to eight hours post-recovery. Glutamate overproduction led to increases in glycine and citrulline, which were observed during recovery and two to eight hours post-recovery.
"These findings suggest that pharmacologic strategies to protect the brain from injury and cell death during HCA will require targeting the excitatory amino acid pathway throughout the cooling process," says Charles J. Lowenstein, M.D., assistant professor of medicine at Hopkins and an author of the paper.
The study's other authors were lead author Elaine E. Tseng, M.D.; Malcolm V. Brock, M.D.; Christopher C. Kwon, M.S.; Jorge D. Salazar, M.D.; John R. Doty, M.D.; Michael V. Johnston, M.D.; and William A. Baumgartner, M.D.
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