Embargoed until 18-Oct-2000
GOLDFISH AND FIREFLIES POINT WAY TO NEW ANESTHESIAREVERSAL DRUG
SAN FRANCISCO -- Imagine having surgery under general anesthesia and then waking up afterward with no residual drowsiness. That could one day become a reality for surgical patients, thanks to the common goldfish, according to researchers at the University of Utah-Salt Lake City.
Using goldfish and a natural substance called myristic acid, the scientists led by Issaku Ueda, M.D., have come one step closer to understanding the molecular basis for anesthesia's effects on the brain.
The researchers' most recent laboratory work, presented at the American Society of Anesthesiologists annual meeting, builds directly on research first conducted in 1942 showing that anesthesia is reversed by an increase in hydrostatic pressure, the pressure that is exerted by a liquid.
"The ability to reverse anesthesia by increasing pressure means that individual protein molecules in the brain under anesthesia are somehow larger than individual molecules in the state of being awake," explained Dr. Ueda, who has conducted research in this area for more than 30 years.
In a previous study, Dr. Ueda and colleagues analyzed the responses of firefly luciferase enzyme to anesthesia using calorimetry and spectroscopy, techniques that calculate changes in substances and present those changes in units of heat and color.
Luciferase, the substance in lightning bugs that makes them light up, also happens to be exceptionally sensitive to anesthesia. The study revealed that anesthetics relax protein molecules and that myristic acid, a fatty acid found in many foods, tightens them.
The researchers concluded that the relaxation of protein molecules is what makes anesthesia possible. "Without volume expansion, anesthesia does not ensue," Dr. Ueda stated.
Armed with that evidence, they set out to test myristic acid's ability to reverse anesthesia in living subjects.
The researchers filled jars of water with three concentrations of myristic acid and a control jar with plain water. Using an anesthesia machine, they bubbled halothane, a common anesthetic gas, into each jar, placed goldfish in each jar for 30 minutes to completely anesthetize them and then stimulated them with a weak electrical current to gauge differences in the fish's reactions. More goldfish "emerged" from anesthesia (began swimming) in the tank containing the highest concentration of myristic acid. As the level of myristic acid decreased, so did the numbers of goldfish who responded to the electrical charge.
The success of the experiment adds new weight to the theory that the expansion of protein volume is the necessary condition for anesthesia, Dr. Ueda said.
The finding could one day help in the development of a drug capable of reversing anesthesia that would be nontoxic and probably have few side effects, Dr. Ueda said.
Such a drug could also be useful for treating malignant hyperthermia, a rare but potentially fatal reaction to some anesthetic medications. The drug would allow anesthesiologists to reverse the effects of those medications more quickly than they can using current medications.
The researchers plan to continue looking at myristic acid's potential as an anesthesia-reversal agent in additional laboratory studies.
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This research will be presented at the 2000 American Society of Anesthesiologists (ASA) annual meeting in San Francisco, California, on October 14-18. During the annual meeting, you can reach communications staff members between 8 a.m. and 5 p.m. in the ASA press room at the Moscone Center, Room 228, telephone: (415) 978-3710. ASA staff members will be on hand to assist you in scheduling interviews, locating individuals and providing general background information.
Most of the news releases are embargoed until their presentation date. If you cannot attend the meeting, members of the ASA communications department can assist you in arranging interviews with the presenters prior to the meeting.
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For more information about ASA, the 1999 Annual Meeting and the medical specialty of anesthesiology, visit our World Wide Web site: http://www.ASAhq.org
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