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Device provides breathing help for research mice

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A miniature respirator developed by MIT engineers is breathing life into newborn mice.

The machine, essentially a tiny version of the iron lung used to treat human polio patients, was built for mutant mice suffering from respiratory distress. These animals, bred to have specific genetic characteristics, are important to the study of genetics and human disease. For example, they can be models for different ailments, allowing researchers to test potential therapies.

Sometimes, however, this genetic manipulation has unintended consequences. Among other things, it can cause respiratory failure that can kill the valuable animals.

"Until now there was nothing available to resuscitate these mice, which represent a major commitment of research time and money," said Dr. Chi-Sang Poon, a principal research scientist in the Harvard-MIT Division of Health Sciences and Technology (HST). (Animals can cost some $200 apiece). "With the new machine we now have a newborn clinic, more or less, for mice."

Dr. Poon developed the full prototype machine -- which is a little bigger than a shoebox -- with Kumaran Kolandaivelu, an MIT undergraduate at the time who is now an HST graduate student. The two are coauthors of a paper on the work in the February issue of the Journal of Applied Physiology. Mr. Kolandaivelu won the 1995 Whitaker Senior Student Bioengineering Design Award from the Biomedical Engineering Society for work reported in the current paper.

As with the iron lung, the mouse is put into a cylindrical chamber (about 5 cm by 2 cm in diameter) with its head sticking out one end. A rubber cuff around the animal's neck seals the chamber. The pressure in the chamber is then raised and lowered repeatedly, causing the animal's lungs to inflate and deflate.

Today's conventional human respirators deliver air via a tube in the neck. This isn't feasible for mice, however, because the animals are too small. "Even if you could insert a tube into the trachea, any bit of moisture would clog up the airways," Dr. Poon said.

The MIT machine, for which a patent is pending, incorporates several novel features. For example, the double pistons that drive the pressure fluctuations in the chamber also prevent the application of too much pressure, which can close the animal's airways.

The machine also allows researchers to explore different modes of ventilation, all revolving around the frequency of the pressures used in the chamber. For example, pressure can be applied in synchrony with the animal's breathing, or at much higher frequencies. "Such adaptability is needed since newborn [mice] have never been tested before, and the proper ventilation techniques are not certain," Dr. Poon and Mr. Kolandaivelu wrote in the JAP article.


Preliminary tests of the machine with one kind of mutant mice are promising. The ventilated mice survived more than 50 percent longer than the absolute life expectancy of these mutants without ventilation. "Indeed, the mutants died only after being weaned from the ventilator," the researchers write.

Dr. Poon has been working on problems related to respiration for some 20 years. In addition to his work with the mouse respirator, he has developed a new ventilation technique for human babies that has been tested on rabbits. He has also invented two different devices to help babies trigger ventilators. One is patented, the other has a patent pending.

Harvard Apparatus Inc., a local scientific instrumentation company, licensed the mouse respirator and will soon market a commercial version. The research was sponsored by the National Heart, Lung, and Blood Institute, the National Science Foundation and the Office of Naval Research.

A version of this article appeared in MIT Tech Talk on March 4, 1998.

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