Neuronal rescue by refrigeration: drug tests yield a chilling surprise

Science News, March 10, 1990 by Rick Weiss

Whatever the future of MK-801, Buchan and Pulsinelli's findings provide new incentive for researchers to investigate the value of inducing lowered body temperatures in patients who have just suffered a heart attack or stroke. For years, surgeons performing operations that may temporarily limit oxygen supplies to the brain have reduced the risk of surgery-related brain damage by chilling patients in advance--generally by placing them in a cooled room and by infusing them with chilled intravenous fluids. And reports of children who have remained submerged in near-freezing water for prolonged periods without apparent brain damage indicate that low brain temperatures during oxygen deprivation can also protect brain neurons. Their new work, Buchan and Pulsinelli say, now clearly indicates that hypothermia of even a few degrees, soon after a loss of oxygen, can have an equally impressive neuroprotective effect.

Given those findings, Pulsinelli and others maintain that a degree of refrigeration might prove useful as an emergency therapy in victims of heart attacks or strokes. But for now, physicians note, hospitals are not prepared to induce hypothermia on an emergency basis.

"The question is, can you do it quickly enough?" says Buchan, now at the University Hospital in London, Ontario. He and others wonder whether any kind of drug can safely lower core temperatures with sufficient rapidity in human beings, whose body masses are substantially greater than those of any animals currently under such investigation.

Along with the challenge of dropping body temperatures quickly, researchers have yet to determine just how cold is cold enough. European researchers, who have reported successfully preventing brain damage in oxygen-deprived newborns by dunking them in chilled water for up to 15 minutes, have noted that longer exposures to temperatures below 29[degrees]C may prove detrimental. Similarly, while some early attempts to chill heart attack victims to 25[degrees]C effectively rescued brain neurons, Buchan says the treatment wreaked metabolic havoc elsewhere in the body. Among other things, the very low temperatures triggered coagulation problems and cardiac arrhythmias.

Recently, researchers have suggested cooling such patients to a more moderate 33[degrees]C. But ideally, Buchan says, physicians would like to cool the brain to these temperatures without having to chill the rest of the body -- thus avoiding the various metabolic side-effects of hypothermia, including the adrenalin release that comes with intense shivering.

Buchan says one approach would be to inject cold saline directly into some of the cavities, or sinuses, in the brain. But so far, he says, no one has tested the approach in a clinical trial.