The 150-year-old riddle of what makes nitroglycerin work as a cardiovascular treatment appears to have been solved by a team of American and Japanese scientists.
But the answer also raises important questions about the safety of the drug as a treatment for chest pain.
In fact, the researchers now advise that, until further studies are conducted, nitroglycerin should be prescribed only in moderation, and not at all to patients already taking a large number of other medications.
"You take it for granted that when a drug is given that we know what we're doing, and that has not been the case for nitroglycerin," said study co-author Dr. Jonathan S. Stamler, of the department of medicine and the Howard Hughes Medical Institute at Duke University Medical Center. "We now finally understand how this drug works for the first time, and that the drug may not be useful in many of the forms it is now given."
Nitroglycerin is one of the oldest cardiovascular drugs -- in continuous use by doctors since 1847. Its benefits for the relief of chest pain were first observed in the Swedish explosives factory of Alfred Nobel -- founder of the Nobel Peace Prize -- where the compound was a key ingredient in dynamite.
The invention helped make Nobel a rich man, with the added bonus of making some of his workers feel better while on the job. Eventually, nitroglycerine's blood vessel-dilating properties became clear, even though the mechanism driving this effect remained murky. The medication ultimately became one of the mainstays of cardiac treatment, but in the absence of the kind of rigorous scientific scrutiny new drugs receive today.
Seeking to shed light on the drug's mechanics, Stamler and his colleagues report in this week's online issue of the Proceedings of the National Academy of Sciences on their work with two groups of mice: one normal and one genetically altered.
The altered mice lacked a specific enzyme, called mtALDH, that's present normally within the cell's 'energy factories,' the mitochondria.
When nitroglycerin was given to the normal mice -- in doses comparable to those given to human patients -- the researchers witnessed a drop in blood pressure that would normally be expected after drug application.
However, when nitroglycerin was given to the mice lacking mtALDH, the drug had no effect on blood pressure.
Based on this result, the team concluded that the mtALDH enzyme is key to nitroglycerin's ability to lower blood pressure.
They explain that mtALDH initiates the breakdown of nitroglycerin into nitric oxide, a 'vasodilator' that opens up blood vessels and lowers blood pressure. Nitric oxide has an important regulatory role in blood vessel dilation, and is normally present in the bloodstream.
But solving the nitroglycerin puzzle may bring a new set of problems.
For one, the interaction between nitroglycerin and certain classes of prescribed medications could cause trouble, the researchers note.
Drugs such as sulfonylureas, used by diabetics; and chloral hydrates, used by patients with sleep disorders; tend to lower mitochondrial enzyme activity and may thereby reduce the effectiveness of nitroglycerin. Even the common use of alcohol or acetaminophen (such as Tylenol) can have a similar effect.
In addition, patients whose mitochondrial enzymes are generally less active -- a genetic condition found most commonly among certain Asian populations -- might not respond well to nitroglycerin, they said.
Finally, Stamler's group worry that cardiac patients using the drug on a long-term basis might, in fact, be damaging their mitochondria over time.
This effect may account for the long-observed drop in nitroglycerin's ability to lower blood pressure when used over the long term.
More seriously, Stamler said, such damage may also lead to a worsening of overall cardiovascular condition -- in effect, rusting out heart cells through oxidation.
Diabetics are at a particular risk for these types of cardiovascular complications due to nitroglycerin use since they typically experience mitochondrial damage even before taking the drug.
"It's really quite an amazing thing," said Stamler. "Nitroglycerin has a very romantic association with science and scientific endeavor. But there is good reason to believe the drug may not be efficacious and might even be dangerous. It's perhaps interesting to point out that Alfred Nobel himself suffered from heart disease, but even he refused to take nitroglycerin -- thinking that no one in his right mind would take an explosive."
"People can be very concerned -- and I am very concerned," added Stamler --cautioning that nitroglycerin's worth as a treatment option can only be validated by large-scale studies.
Dr. David A. Kass, a professor of medicine and biomedical engineering at Johns Hopkins Medical Institutions in Baltimore, countered that while further studies are never a bad idea he sees no evidence to suggest that anyone taking nitroglycerin should be alarmed.
"It's not that we've identified something that's very troubling and disturbing, or that people are dying," he said. "I don't think there's any meaningful data to suggest that nitrates taken chronically, in fact, kill you. There's certainly data to suggest that nitrates taken chronically are ineffective. And this study has described a new mechanism for why you might lose this effectiveness. But whether this leaves you more vulnerable or not I think is very speculative."
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Health Tip: Finding an Eye Doctor
Regular eye exams are key to maintaining healthy eyes.
The National Eye Institute offers these tips for finding the right eye-care professional:
Ask family and friends about ophthalmologists or optometrists they use. Ask your family doctor for a recommendation. Contact a state or county association of ophthalmologists or optometrists. Ask your insurance company whether it has a list of eye-care professionals covered under your plan.
Health Tip: Safe Use of Baby Strollers
Strollers make babies more transportable and life more convenient. But as handy as they may be, strollers aren't risk free.
Each year, hundreds of children end up in emergency rooms because of falls, pinches and tipovers from strollers, according to the American Academy of Family Physicians.
Here are some safety tips for correct stroller use:
Always supervise your child when he or she is in a stroller. Older kids may try to climb out. Use the restraint system that comes with your stroller. Avoid hanging shopping bags or purses over the stroller's handles. This will help prevent tipping. If your stroller malfunctions and your child is hurt, report the problem to the U.S. Consumer Product Safety Commission or similar government agency.
A well-stocked first-aid kit, kept within easy reach, is a necessity in every home. Having supplies gathered ahead of time will help you handle an emergency at a moment's notice. You should keep one first-aid kit in your home and one in each car. Also be sure to bring a first-aid kit on family vacations.
Choose containers for your kits that are roomy, durable, easy to carry, and simple to open. Plastic tackle boxes or containers for storing art supplies are ideal, since they're lightweight, have handles, and offer a lot of space.
Include the following in each of your first-aid kits:
first-aid manual sterile gauze adhesive tape adhesive bandages in several sizes elastic bandage antiseptic wipes soap antibiotic cream (triple-antibiotic ointment) antiseptic solution (like hydrogen peroxide) hydrocortisone cream (1%) acetaminophen and ibuprofen extra prescription medications (if the family is going on vacation) tweezers sharp scissors safety pins disposable instant cold packs calamine lotion alcohol wipes or ethyl alcohol thermometer plastic gloves (at least 2 pairs) flashlight and extra batteries mouthpiece for administering CPR (can be obtained from your local Red Cross) your list of emergency phone numbers blanket (stored nearby)
After you've stocked your first-aid kits:
Read the entire first-aid manual so you'll understand how to use the contents of your kits. (If your children are old enough to understand, review the manuals with them as well.) Store first-aid kits in places that are out of children's reach but easily accessible for adults. Check the kits regularly. Replace missing items or medicines that may have expired.
Health Tip: Treating Ringworm
Scaly, ring-shaped, pink patches on the skin or scalp may indicate ringworm, a fungal infection.
Children's Healthcare of Atlanta offers these treatment tips:
Check with your doctor before applying treatment. Other skin problems can mimic ringworm. Apply an anti-fungal cream to the rash and one inch beyond the edge of the rash. Keep using the cream for one week after the rash has gone. Avoid scratching the area.
Ringworm doesn't spread easily and is not contagious.
Health Tip: When to Change a Toothbrush
Your child's most important tool for preventing tooth decay and cavities is his or her toothbrush, the Children's Hospital of Philadelphia reminds us.
Here are some pointers for toothbrush selection and care:
When shopping for a toothbrush, select about three appropriate styles and then let your child choose the one he or she likes most. Make sure your child cleans his toothbrush thoroughly after each use, and stores it in a dry place. Change your child's toothbrush every three months, or sooner if the bristles become bent or stiff. If your child gets sick, replace the toothbrush after he's recovered.
Food Fact: Got your bacteria?
Yogurt is crawling with bacteria -- and the more of it you eat, the better. Be sure to buy yogurt with a seal that guarantees it has live, active cultures. These cultures -- especially acidophilus and bifida -- colonize the lower intestines with beneficial bacteria while muscling out disease-causing bacteria. Eating yogurt may help prevent diarrhea in people taking antibiotics. Yogurt is easy to digest, especially for those who are lactose-intolerant, and is an excellent source of calcium, protein, riboflavin (a B vitamin), vitamin B-12 (which may be low in vegetarian diets) and vitamin A. To avoid unwanted saturated fat, choose nonfat or low-fat yogurt.
Fitness Tip of the day: We've got your back!
Back feeling sore after exercising? Take our tip to relieve tension. If back muscles become tight and sore after exercise -- a common feeling -- a great way to relieve this stress is to lie on the floor with a tennis ball between your back and the floor and give yourself a massage.
FAQ of the day: Should I worry about eating proteins at each meal?
Pairing foods to provide all essential amino acids at one meal is no longer considered critical for vegetarians. Plant proteins are not as complete in all essential amino acids as animal proteins, so it became common advice for vegetarians to eat a food low in one essential amino acid in tandem with another that was high in that particular amino acid. But as scientists learned more about protein metabolism, they discovered that the body maintains a pool of amino acids it draws from to fill any gaps from meal to meal. There's no need to worry about matching foods at meals, as long as you eat a varied diet. Soy foods in particular are excellent sources of essential amino acids.