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Dr. André Diedrich and collaborators in the Vanderbilt University Autonomic Dysfunction Center have received a grant from the National Institute on Aging to develop a bionic blood pressure control system for patients with multiple system atrophy, also called Shy-Drager syndrome. (photo by Dana Johnson)

Bionic blood pressure device being developed at Vanderbilt

BY: LEIGH MACMILLAN

9/06/2002 - Wild swings in blood pressure are the norm for patients suffering from multiple system atrophy, a progressive neurodegenerative disorder of the autonomic nervous system. When these patients stand, their blood pressure plummets; when they are lying down, it soars.

It is a medical challenge to treat both hypotension and hypertension in the same patient, said Dr. André Diedrich, research assistant professor of Medicine.

“These patients cannot stand up. They are severely disabled and unable to work,” he said. “Drugs sometimes help, but they never restore function completely. We need new treatment options.”

Diedrich and collaborators in the Vanderbilt University Autonomic Dysfunction Center have received a grant from the National Institute on Aging to develop a bionic blood pressure control system for patients with multiple system atrophy, also called Shy-Drager syndrome. Diedrich is hopeful that someday these patients could be outfitted with a bionic system that would automatically sense their changing blood pressure and stimulate nerves to keep it within normal limits.

“Of course it’s very futuristic,” Diedrich said, “but the idea is that — like the pacemaker for the heart — we would create a pacemaker for blood pressure.”

Diedrich’s “pacemaker for blood pressure” would replace a defective baroreflex response in multiple system atrophy patients. The baroreflex system is a control system that fine-tunes blood pressure, keeping it within a normal range of values. The system depends on “baroreceptors” — specialized receptors located in the blood vessels — that sense blood pressure and notify an area of the brain called the vasomotor center when adjustments are needed. The vasomotor center, in turn, adjusts blood pressure by controlling sympathetic nerve traffic and thereby changing heart rate and blood vessel constriction.

“The idea is to replace the vasomotor center with a type of microcomputer system which will sense the blood pressure and will somehow stimulate the nerves to change blood pressure,” Diedrich said.

The bionic system depends on the patients having intact sympathetic nerves that can be stimulated — which is the case for multiple system atrophy patients. Diedrich participated in the studies, which demonstrated that, in contrast to previous beliefs, these patients do have functional sympathetic nerves, but that these nerves are no longer controlled by the brain.

Diedrich and colleagues will use a rat model system in which the baroreflex has been surgically interrupted to develop prototypes of their bionic baroreflex. They will stimulate nerves in the spinal column using a variety of frequencies and study the blood pressure responses. These early studies will inform the development of algorithms that allow computerized blood pressure control.

The investigators have selected epidural nerve stimulation as a model because they hope to test their ideas in patients with previously implanted epidural spinal stimulators for pain relief. The FDA-approved epidural spinal stimulator system can deliver varying frequencies and amplitudes of stimulation to achieve maximal pain relief. Depending on the frequencies used for stimulation, Diedrich said, blood pressure modulation may also occur.

“For pain relief, the stimulator works in a certain mode, but if you change that mode, by varying the frequency or amplitude, you might see large effects on blood pressure,” he said. There is a period of time following stimulator implantation, Diedrich said, when patients try different frequencies and amplitudes of stimulation in order to find the optimal mode for preventing pain. “We simply want to record how the blood pressure changes as patients perform this optimization.” These simple blood pressure recordings could open the door for using these epidural stimulators to regulate blood pressure.

Preliminary studies in animals demonstrated the feasibility of the approach. “If we gave low frequency stimulation, we decreased the blood pressure, and if we gave high frequency stimulation, we increased the blood pressure,” Diedrich said. “If this is true in human beings, it would be perfect for our patients with multiple system atrophy.”

Diedrich’s grant is a special type of NIH grant called a Small Business Technology Transfer (STTR) grant. The STTR program is intended to facilitate the application of technologies invented at academic institutions to practical use in society. It funds projects that involve cooperation between university scientists and small businesses. Diedrich will be working with TkTx Co., founded by former Vanderbilt faculty members Drs. Arlene Stecenko and Kenneth Brigham. He will also collaborate with Dr. Peter E. Konrad, assistant professor of Neurological Surgery, and with Drs. Kenji Sunagawa and Takayuki Sato, specialists in the field of bionics at the National Cardiovascular Center in Osaka, Japan.

Up to 100,000 Americans are estimated to suffer from multiple system atrophy and could benefit from a bionic blood pressure device, Diedrich said. And the device might be useful to other patients with an uncoupling of the baroreflex system, such as those with spinal cord injuries, he said.

Diedrich started his efforts to develop a bionic blood pressure control system with funding from Vanderbilt’s Intramural Discovery Grant program, which he credits for his success in securing a NIH grant. “As a young scientist I did not have much opportunity for funding,” he said. “The Discovery Grant I received through Vanderbilt really allowed me to do the preliminary studies that led now to this STTR grant.”

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