VUMC Reporter: VUMC team nets $9.5 million to study autonomic nervous system

[Guest guest]

Don Summers has sent you an article from the VUMC Reporter

http://www.mc.Vanderbilt.Edu/reporter/index.html>

Dr. on will be one of the physicians attending our meeting in Chicago

Sept. 12-15 2001

See our Website www.shydrager.com for more information.

You may read this story online at:

http://www.mc.Vanderbilt.Edu/reporter/index.html?ID=2182>

------

Fortunately, there are some things we don’t have to think about doing. We don’t

have to consciously keep our hearts beating steadily; we don’t have to change

our blood pressure to avoid fainting when we stand. The autonomic nervous system

takes care of these things for us.

But it can run into problems. A group of VUMC investigators has received a $9.5

million, five-year Program Project Grant (PPG) from the National Heart, Lung,

and Blood Institute to study disorders of the autonomic nervous system. The

grant is a renewal and expansion of a PPG that was first awarded in 1997.

“We doubled the size of our initial program, and the reviewers seemed to like

it,” said Dr. on, professor of Medicine, Pharmacology, and

Neurology, director of the Clinical Research Center, and principal investigator

of the grant. “It is said to be the only fully patient-oriented research PPG in

the heart institute.”

Program Project Grants support a group of investigators “with the idea that we

can do more together than we could ever do on our own,” on said. “We’ve

put together a group of investigators with the mission of understanding the

pathophysiology of autonomic nervous system disorders so we can treat these

disorders more effectively.”

Disorders of the autonomic nervous system usually cause very high or very low

heart rates or blood pressures, on said. The most common of these

disorders is orthostatic intolerance — a syndrome characterized by an increase

in heart rate (at least 30 beats per minute) on standing. For someone who

suffers from orthostatic intolerance, the simple act of standing causes a racing

heart, nausea, headache, dizziness, and even fainting. The disorder affects more

than 500,000 people in the United States.

“Orthostatic intolerance can be debilitating,” on said.

on and a core group of investigators formed the Vanderbilt University

Autonomic Dysfunction Center in 1978 to treat and study patients with

orthostatic intolerance and other disorders of the autonomic nervous system. “We

were the first center to specifically focus on these disorders,” on said,

“so we have probably seen more patients than any other center in the world.”

The long history of patient care and research in this area provides an

invaluable tool for on and his co-investigators — a database of clinical

information accumulated over the years. And now DNA data are being collected and

added to the database, on said. The large number of patients has allowed

center investigators to identify previously unrecognized syndromes and develop

new treatments.

“When we discover a new cause for one of these clinical autonomic syndromes,”

on said, “that rapidly leads to improved therapy, and in some cases, it

leads to unique and specific therapy that can reverse the clinical symptoms.”

The overall goal of the current PPG is to achieve better understanding of how

the brain exerts control over the autonomic nervous system, and how that control

plays out in regulating the cardiovascular system. “This program should lead

directly to improved therapy in cardiovascular disease,” on said.

The projects and their leaders are:

• Project 1, led by on, will focus on the changes that occur in human

subjects when the norepinephrine transporter — a sort of molecular vacuum

cleaner that removes neurotransmitter from the synapse — is blocked. Project 1

also will seek to understand why variable amounts of plasma leak out of the

blood vessels when individuals stand, on said.

• Project 2, led by Randy D. Blakely, Ph.D., Allan D. Bass Professor of

Pharmacology and director of the Center for Molecular Neuroscience, will search

for genetic alterations in the norepinephrine transporter in cardiovascular

disorders linked to autonomic dysfunction. This project will be the first

systematic attempt to find such genetic changes, Blakely said. The project will

also look for evidence of disrupted cardiovascular function and transporter

mutations in patients more typically evaluated in psychiatric medicine, for

example patients with depression or attention deficit hyperactivity disorder.

• Project 3, led by Dr. Italo Biaggioni, associate professor of Medicine and

Pharmacology, will study the role of nitric oxide — a chemical that relaxes

smooth muscle and dilates blood vessels — in governing blood pressure control.

• Project 4, led by Dr. Rose M. on, professor of Medicine, will examine

baroreflex failure and its clinical manifestations. The baroreflexes maintain

arterial blood pressure within a narrow range, in order to protect blood flow to

critical organs like the brain. Baroreflex failure causes patients to have

severe volatile high blood pressure.

• Project 5, led by Dr. N. , Rudolph H. Kampmeier Professor of

Medicine, will study the mechanism by which hypoglycemia (low blood sugar) and

other stressors can lead to autonomic dysfunction in patients with diabetes.

[Guest guest]

THANK GOD! I am jumping up and down happily in my mind. .

Hopefully, Dr. on will come up with a new drug like he did

before (i.e. Proamatine). Hopefully, the Vanderbilt Group will develop

new and improved drug therapy and more knowledge of the autonomic

system. People here have been helping me cross my legs, raise and lower

them, sit me down, up , walk, sleep, dress, bath, p.t.., water therapy,

turn on and off air conditioners, fans, and on and on.

Bless the reviewers for renewing this grant.

Thanks so much for this news! I wish I could make it to Chgo. for the

conference. That is where I grew up.

nancy mullen

HTTP User wrote:

>

> Don Summers has sent you an article from the VUMC Reporter

> http://www.mc.Vanderbilt.Edu/reporter/index.html>

>

> Dr. on will be one of the physicians attending our meeting in Chicago

Sept. 12-15 2001

> See our Website www.shydrager.com for more information.

>

> You may read this story online at:

> http://www.mc.Vanderbilt.Edu/reporter/index.html?ID=2182>

>

> ------

>

> Fortunately, there are some things we don’t have to think about doing. We

don’t have to consciously keep our hearts beating steadily; we don’t have to

change our blood pressure to avoid fainting when we stand. The autonomic nervous

system takes care of these things for us.

> But it can run into problems. A group of VUMC investigators has received a

$9.5 million, five-year Program Project Grant (PPG) from the National Heart,

Lung, and Blood Institute to study disorders of the autonomic nervous system.

The grant is a renewal and expansion of a PPG that was first awarded in 1997.

> “We doubled the size of our initial program, and the reviewers seemed to like

it,” said Dr. on, professor of Medicine, Pharmacology, and

Neurology, director of the Clinical Research Center, and principal investigator

of the grant. “It is said to be the only fully patient-oriented research PPG in

the heart institute.”

> Program Project Grants support a group of investigators “with the idea that we

can do more together than we could ever do on our own,” on said. “We’ve

put together a group of investigators with the mission of understanding the

pathophysiology of autonomic nervous system disorders so we can treat these

disorders more effectively.”

> Disorders of the autonomic nervous system usually cause very high or very low

heart rates or blood pressures, on said. The most common of these

disorders is orthostatic intolerance — a syndrome characterized by an increase

in heart rate (at least 30 beats per minute) on standing. For someone who

suffers from orthostatic intolerance, the simple act of standing causes a racing

heart, nausea, headache, dizziness, and even fainting. The disorder affects more

than 500,000 people in the United States.

> “Orthostatic intolerance can be debilitating,” on said.

> on and a core group of investigators formed the Vanderbilt University

Autonomic Dysfunction Center in 1978 to treat and study patients with

orthostatic intolerance and other disorders of the autonomic nervous system. “We

were the first center to specifically focus on these disorders,” on said,

“so we have probably seen more patients than any other center in the world.”

> The long history of patient care and research in this area provides an

invaluable tool for on and his co-investigators — a database of clinical

information accumulated over the years. And now DNA data are being collected and

added to the database, on said. The large number of patients has allowed

center investigators to identify previously unrecognized syndromes and develop

new treatments.

> “When we discover a new cause for one of these clinical autonomic syndromes,”

on said, “that rapidly leads to improved therapy, and in some cases, it

leads to unique and specific therapy that can reverse the clinical symptoms.”

> The overall goal of the current PPG is to achieve better understanding of how

the brain exerts control over the autonomic nervous system, and how that control

plays out in regulating the cardiovascular system. “This program should lead

directly to improved therapy in cardiovascular disease,” on said.

> The projects and their leaders are:

> • Project 1, led by on, will focus on the changes that occur in human

subjects when the norepinephrine transporter — a sort of molecular vacuum

cleaner that removes neurotransmitter from the synapse — is blocked. Project 1

also will seek to understand why variable amounts of plasma leak out of the

blood vessels when individuals stand, on said.

> • Project 2, led by Randy D. Blakely, Ph.D., Allan D. Bass Professor of

Pharmacology and director of the Center for Molecular Neuroscience, will search

for genetic alterations in the norepinephrine transporter in cardiovascular

disorders linked to autonomic dysfunction. This project will be the first

systematic attempt to find such genetic changes, Blakely said. The project will

also look for evidence of disrupted cardiovascular function and transporter

mutations in patients more typically evaluated in psychiatric medicine, for

example patients with depression or attention deficit hyperactivity disorder.

> • Project 3, led by Dr. Italo Biaggioni, associate professor of Medicine and

Pharmacology, will study the role of nitric oxide — a chemical that relaxes

smooth muscle and dilates blood vessels — in governing blood pressure control.

> • Project 4, led by Dr. Rose M. on, professor of Medicine, will examine

baroreflex failure and its clinical manifestations. The baroreflexes maintain

arterial blood pressure within a narrow range, in order to protect blood flow to

critical organs like the brain. Baroreflex failure causes patients to have

severe volatile high blood pressure.

> • Project 5, led by Dr. N. , Rudolph H. Kampmeier Professor of

Medicine, will study the mechanism by which hypoglycemia (low blood sugar) and

other stressors can lead to autonomic dysfunction in patients with diabetes.

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