Press Releases

Mayo Clinic in Rochester
Tuesday, October 05, 2004

Mayo Clinic Finds Effective Remedy for Blood Pressure Drop When Standing Up

ROCHESTER, Minn. -- Mayo Clinic neurologists have discovered a drug application smart enough to alleviate orthostatic hypotension -- problems with sinking blood pressure when standing up from a sitting position -- without the unwanted effect of also causing patients' blood pressure to soar when lying down.

"This is a significant step forward for these patients," says Phillip Low, M.D., Mayo Clinic neurologist and lead study investigator. "This would be a good drug to provide the first line of treatment."

The drug, pyridostigmine, has been used for years for myasthenia gravis, a neuromuscular transmission disorder. Dr. Low hypothesized that it would also improve nerve cell transmission for orthostatic hypotension patients and trigger the reflex that controls blood pressure in all positions.

Of the 58 patients in Dr. Low's study, one-third were able to stop taking any other orthostatic hypotension medications, and others were able to lower the amount of other drugs needed. Orthostatic hypotension is especially common in those over age 70. In general, blood pressure control lessens as one ages, according to Dr. Low. Common causes of orthostatic hypotension include diabetes, autonomic neuropathy, multiple system atrophy, pure autonomic failure and Parkinson's disease. Certain drugs, such as diuretics and medication used to control blood pressure, are also common catalysts for the condition. Studies conducted at Mayo Clinic by Peter Dyck, M.D., neurologist, indicate 10 percent of diabetics have orthostatic hypotension.

The challenge with trying to fix this condition, according to Dr. Low, is that most medications that increase blood pressure raise blood pressure in all positions. Thus, the drugs would work for patients with orthostatic hypotension when they stood up, but their blood pressure would be too high when lying down, increasing their risk of stroke. Dr. Low felt that this price was too high, and that treating with medications that raised blood pressure while standing but raised blood pressure while lying down amounted to trading one problem for another.

"We wanted a ‘smart drug' that would only increase blood pressure when standing up, and not when lying down," says Dr. Low. Pyridostigmine works at the level of the autonomic ganglion, which has minimal nerve signaling traffic when lying down. When standing up, however, nerve signaling traffic in the autonomic ganglion increases, so the researchers theorized that a drug that affected the autonomic ganglion would improve orthostatic hypotension patients' standing blood pressure but not increase the blood pressure while lying down.

After a small, open trial of 15 subjects in which the pyridostigmine performed effectively as hoped, the investigators proceeded to the current double-blinded study of 58 patients. The patients either received placebo, pyridostigmine alone or pyridostigmine in combination with one of two low dosages of midodrine, a drug previously proven to improve orthostatic hypotension.

The effects of the drugs were measured one hour post-treatment. Pyridostigmine significantly improved the patients' standing blood pressure without elevating blood pressure while lying down. The positive effects of the drug were even further improved when combined with low-dose midodrine. Improvement of blood pressure was associated with improvement of symptoms while standing.

Side effects from pyridostigmine were minor and transient, including some abdominal cramping or need to go to the bathroom more often than usual.

Paola Sandroni, M.D., another Mayo Clinic neurologist, conducted a follow-up study of the first 45 patients in the study led by Dr. Low; the follow-up study occurred an average of 19.5 months after the first trial. Detailed information was available on 32 patients, and 75 percent reported either good or excellent results from the pyridostigmine treatment. Approximately one in four were able to manage on pyridostigmine alone, and one in three needed other medications, yet were able to reduce the dose of the other medication (e.g., midodrine or fludrocortisone).

"By the time they come to see us at Mayo Clinic, the majority of our orthostatic hypotension patients have had multiple treatments and have not done very well," says Dr. Low. "They are very grateful to have found this drug [pryridostigmine]."

The next step in the orthostatic hypotension research will involve seeking out an even smarter drug combination involving pyridostigmine that might work on multiple levels.

A Program Project Grant for research in autonomic disorders, which was first awarded to Dr. Low by the National Institutes of Health in 1996, funded this study.

http://www.mayoclinic.org/news2004-rst/2451.html

PUBLIC RELEASE DATE: 14-NOV-2000
Contact: Carole Bullock or Bridgette McNeill
504-670-4000
American Heart Association

Food in flight fights fainting spells and heart attacks

NEW ORLEANS, Nov. 15 - Having a quick snack and a non-alcoholic drink before boarding a plane can lower your chances of becoming an in-flight emergency statistic, according to a study presented today at the American Heart Association's Scientific Sessions 2000.

"There are many reports that in-flight medical emergencies are generated at the rate of one person per 800 to1,900 flights," says primary researcher Makoto Matsumura, M.D., of the Saitama Medical School in Japan. More than half of these involve the loss of consciousness and heart attack. Factors such as anxiety, the environment inside the cabin, dehydration, prolonged sitting and alcohol use have been suggested as causes of these emergencies, but no one has researched these explanations or how the problem can be prevented. This study is the first to evaluate the role of food and fluids in preventing fainting and heart attacks in air travelers. The researchers say that eating and drinking before boarding was expected to raise the volume of blood circulating in the body.

"Having something to eat and drink is the simplest method of increasing the circulating blood volume for air travelers. Most are probably doing it before boarding anyway, but people need to know it is easy for their bodies' oxygen levels to drop if they don't eat or drink before boarding," says Matsumura. "Medical personnel and travelers should know that hunger can cause in-flight emergencies, and fluid is probably even more effective in preventing emergencies. Older individuals and those with high blood pressure or vascular disorders are especially at risk for these types of emergencies."

Researchers theorized that in-flight fainting spells and cardiopulmonary emergencies could be related to a change in blood-circulation. Low cabin pressure at higher altitudes causes blood vessels in the peripheral circulation and organs to expand as the body attempts to increase its oxygen supply. However, the amount of blood pumped by the heart remains the same. Therefore, everyone on the plane - from infants to the elderly, crew and passengers - could have a relative reduction in oxygen supply throughout their bodies.

"Many people experience an unpleasant feeling in-flight. I sometimes get a headache or feel cold or tired, which is similar to the slight sickness caused by low in-flight air pressure. Treatment is usually unnecessary. However, in some cases, a doctor is needed during a flight in case the person is having a heart attack," says Matsumura. "We wanted to know what causes this oxygen reduction." Blood pressure does not change if the circulating blood volume is high enough. However, it is possible to have a blood-pressure decrease and oxygen deficiency in the organs if the amount of blood circulating in the body is too low to accommodate expanded blood vessels, and this may be affected by dehydration, says Matsumura.

The study was performed in a hypobaric (low barometric pressure) training laboratory for Japan's Air Force pilots in which barometric pressure can be completely controlled. Researchers simulated conditions equal to the pressure of a flight to 10,000 feet. Using non-invasive measures, they measured heart function, blood flow and oxygen saturation of both brain and organ tissues in 12 normal volunteers. The tests were performed after a 12-hour fast and after eating and drinking.

In the fasting volunteers, reduced cabin air pressure caused no change in heart function or blood flow volume, but blood pressure decreased by about 4 mm/Hg, and oxygen saturation decreased in the peripheral arteries by about 11 percent, and in the brain by about 6 percent.

Eating and drinking caused no significant change in blood pressure, but it did increase cardiac output and blood flow to the brain as tracked through the right carotid artery. Food and fluid intake also improved the levels of oxygen in the peripheral organs by 21 percent, and in the brain by 48 percent over the fasting individuals.

So how much do people need to eat and drink to ward off an emergency situation?

"It is a difficult question to answer," Matsumura acknowledges. "We asked the volunteers to have at least 16 ounces of a soft drink with electrolytes at lunch. Then we measured their body weight. The average weight gain after lunch was about 2.5 pounds, which is appropriate in normal cases. If a large amount of food and fluid increases the circulating volume too much, it may induce heart failure in people who have heart disease." Electrolytes are molecules of calcium, potassium, sodium and other elements that gain a slight electric charge when dissolved in water and are involved in the normal function of the body's cells. These substances are often added to sports drinks.

Researchers plan to increase the number of subjects in future studies that will test the content and volume of food and fluid intake against changes in oxygen saturation and blood flow.

Co-authors are Ryozo Omoto, Shunei Kyo and Akio Nakamura.

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