Science of the soldier’s heart
One of the more curious medical maladies is a condition euphemistically called “soldier’s heart” or “head rush” disorder.
The formal medical description is “orthostatic intolerance,” a disorder of the autonomic nervous system that causes a racing heart, nausea, headache, dizziness and fainting when a person stands up. It affects more than 500,000 people in the United States.
Researchers at Vanderbilt University Medical Center have made significant contributions—dating back 70 years—to understanding this disorder and how the nervous system regulates heart rate and blood pressure.
Their research, supported in a substantial way by the National Heart, Lung, and Blood Institute (NHLBI), illustrates how the study of a relatively rare disease can help advance an entire field. It also demonstrates the importance of public-private partnerships in research.
The autonomic nervous system is the crucial link between the brain and the cardiovascular system. It controls vital systems including blood pressure and heart rate for the most part without conscious control or sensation.
Part of the autonomic nervous system, the sympathetic nervous system, responds to stressors of various kinds by releasing the neurotransmitter norepinephrine. In turn, norepinephrine binds to adrenergic receptors to increase heart rate and blood pressure.
Advances in the treatment of orthostatic intolerance include the use of fludrocortisones, synthetic steroids that raise blood pressure. They were introduced in 1956 by the late Grant Liddle, M.D., former chair of Medicine at Vanderbilt.
On the flip side, John Oates, M.D., founding director of the Vanderbilt Division of Clinical Pharmacology, discovered that methyldopa lowered blood pressure by impairing noradrenergic function.
In 1978, David Robertson, M.D., and his wife, Rose Marie Robertson, M.D., established at Vanderbilt the first center devoted exclusively to the study of autonomic disorders. With a current database of 2,900 patients, the Autonomic Dysfunction Center may be the world’s largest registry of autonomic disorders.
In 1986, the Vanderbilt group reported that a rare, inherited deficiency in the enzyme that makes norepinephrine can cause orthostatic intolerance, and developed a successful drug therapy to treat the deficiency.
In 2000, David Robertson, Randy Blakely, Ph.D., Italo Biaggioni, M.D., and their colleagues described the first genetic defect in orthostatic intolerance—a mutation in the norepinephrine transporter, which regulates the supply of the neurotransmitter in the synapses, or spaces between nerve cells.
Jens Jordan M.D., now at the Franz-Volhard Center for Clinical Investigation in Berlin, discovered while at Vanderbilt in 2000 that drinking water profoundly increases blood pressure in patients with autonomic failure. In 2002, Jordan and coworkers found that drinking water elicited a previously unrecognized physiological reflex and can be used to treat orthostatic intolerance and prevent fainting.
The researchers have since described the mechanisms of other autonomic disorders, including abnormalities in the choline transporter, which is essential to the production of the neurotransmitter acetylcholine.
In 1997, the Vanderbilt researchers received a major Program Project Grant (PPG) from the NHLBI to support their studies of autonomic cardiovascular regulation. That grant has been renewed twice, most recently this summer.
It is the only cardiovascular PPG based solely on clinical, patient-oriented research.
Researchers currently are exploring how variations in the choline transporter may contribute to heart rhythm disorders, the role of the autonomic nervous system in the cardiovascular and metabolic alterations associated with obesity, and how factors such as exercise can affect the autonomic response to hypoglycemia (low blood glucose) in people with diabetes.
David Robertson, who also directs the Elliott V. Newman Clinical Research Center at Vanderbilt, says patients are “absolutely critical” members of the research team. Their experiences have helped advance understanding about how bright light, hyperventilation and drinking water can affect blood pressure.
“I wish we could better harness that knowledge,” he says. “I wish we could learn the things that people have discovered in themselves. If we could harness that, it could really be great for medical science.”