Mayo Clinic researchers have developed a drug treatment to stop the dizziness, light-headedness and fainting that patients experience who suffer from a common form of impaired nerve transmission known as "autonomic failure."
The failure of autonomic nerve function leads to the sudden drop in blood pressure that causes dizziness, and is a frequent side effect of diabetes and Parkinson’s Disease, among others. It occurs when a patient suddenly changes body position, from lying down to standing up. The medical term for this sudden dip in blood pressure is "orthostatic hypotension."
Results from the Mayo Clinic study of 15 patients treated with the drug pyridostigmine are so encouraging that medical journal editorial writer Ronald Schondorf, M.D., Ph.D., describes it as "a potentially ideal therapeutic agent." Commenting on the Mayo Clinic research report that appears in this month’s Journal of Neurology and Neurosurgical Psychiatry, http://jnnp.bmjjournals.com, Dr. Schondorf says in the accompanying editorial that "it is evident that a drug that would function without troubling side effects would be very desirable."
No drug treatments that are free of side effects are currently available to treat orthostatic hypotension. The most dangerous side effect of available treatments is increased stress on the heart from high blood pressure when the patient is lying down.
Phillip Low, M.D., Mayo Clinic neurologist and senior author of this study, describes the significance of the work this way: "What this drug does is reduce the fall in blood pressure when patients stand up. That’s good. That’s what we want because it stops the dizziness. At the same time, the drug has no effect on the lying-down blood pressure -- that’s also good, because that doesn’t stress the heart and brain. So we have the best of both worlds; no dizziness and no stress on the heart and brain. It really works like a magic bullet that way." Mayo Clinic’s Research
In their study, Dr. Low and colleagues focused on the body’s system that detects a fall in blood pressure called baroreflex. It’s a two-part system that sends a message to the brain. The first part of baroreflex tells the heart to speed up. The second part of the baroreflex sends messages down the spinal cord into the blood vessels, signaling them to constrict to bring blood pressure back up. Dr. Low and colleagues concentrated on autonomic signaling.
In their study they report that the signaling system is a two-neuron system that meets at a body part that is like a relay station for nerve messages. It’s called the autonomic ganglia.
The presence of the drug pyridostigmine improves nerve communication at this site at the time when patients with impaired baroreflex most need it: when they stand up.
The drug pyridostigmine works by blocking a compound that otherwise would break down a key nerve-communicating chemical. This block allows the key nerve-communicating chemical to do its job so the blood vessels get the message to stop blood pressure from falling.
Explains Dr. Low: "When you are lying down, nerve traffic through that ganglia is very minimal. When you stand up, nerve traffic picks up. But as a result of the blocking done by pyridostigmine, nerve traffic through the ganglia is enhanced so the ganglia can communicate more effectively the message to blood vessels to constrict."
Researchers also found another positive effect of the drug: It relieves a second common condition patients with autonomic failure experience, constipation. The drug helps by increasing activity in the colon.
This research was performed at Mayo Clinic’s General Clinical Research Center.
Background: The Problem
The change of the body from the lying-down, horizontal position to the standing-up, vertical position is performed effortlessly by most people. When there is no autonomic nerve damage, the body flawlessly and automatically accommodates this by moving most of the three cups of blood that need to be transferred from the chest to the blood vessels of the lower trunk within 10 seconds. It does this by speeding up the heart rate and adjusting vessel tension. The remainder of the blood is transferred within three to five minutes. But in patients who have suffered damage to the baroreflex that maintains normal blood pressure, these compensatory pumping and vessel-stress adjustments are not made.
The Mayo Clinic pioneered the diagnosis and advanced treatment of autonomic nerve function disorder in 1983 when Dr. Low designed the first laboratory and a comprehensive series of tests for evaluating patients with this disorder. He is director of the Mayo Autonomic Disorders Project. As the first program grant for autonomic disorders to be funded by the National Institutes of Health, it is currently running three NIH studies.
Dr. Low says that as encouraging as these early results with the drug pyridostigmine are, results from the NIH-funded trials now underway at the Mayo Clinic are needed to confirm these early findings. If they do, the drug will likely then be a candidate for general prescriptive use.
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