MIT's Mini Respirator Breathes Life Into Mutant Mice

Sometimes, however, this genetic manipulation has unintended consequences. Among other things, it can cause respiratory failure that can kill the 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). (Individual animals can cost some $200 on the market.)

"With the new machine we now have a newborn clinic, more or less, for mice."

Dr. Poon developed the machine 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.)

HOW IT WORKS

As with the iron lung, the mouse is put into a cylindrical chamber, its head sticking out one end. A rubber cuff around the animal's neck seals the chamber. The pressure in the chamber is then oscillated up and down, causing the animal's lungs to inflate and deflate.

In contrast, today's conventional 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, which is patent pending, incorporates several novel features. For example, the double pistons that drive the pressure fluctuations in the chamber prevent the application of too much pressure, which can close the animal's airways.

In addition, the machine allows researchers to explore different modes of ventilation, all revolving around the frequency of the pressure applied in the chamber. For example, the 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 write in the JAP article.

PRELIMINARY TESTS

Preliminary tests of the machine with one kind of mutant mice are promising. The ventilated mice survived over 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 gadgets to help babies trigger ventilators. One is patented, the other 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.