In an ironic twist, researchers report that the classic heart-protecting medication nitroglycerin may actually cause heart attacks to be more severe if given over a prolonged period. But administering another medication along side it may bring the risk back down to virtually nil, so that its protective effect alone can be experienced.
Hospitals typically give nitroglycerin in cycles: 16 hours on the medication, and eight hours off. But the new findings suggest that even this length of cycle time may not be completely safe.
Nitroglycerin has long been given to people who are suffering angina (chest pain) and to heart attack patients to improve blood flow. The medication works by opening up blood vessels so that the heart can receive more oxygen-rich blood. But when given over a prolonged period of time, as it often is in hospitals, an effect called desensitization can occur, in which blood flow is actually reduced, making the heart attacks that do occur more severe.
Though nitroglycerin treatment is old, delving into its full effects in the laboratory is new. Study author Daria Mochly-Rosen says, “Here is a practice in medicine used for over 100 years. Nitroglycerin is so old that a proper clinical trial has never been formally done. Our study says it’s time for cardiologists to examine the value of nitroglycerin treatment that extends for hours at a time.”
Luckily, the researchers also found an effective fix. Giving an enzyme activator Alda-1 seemed to reverse the damaging effects of nitroglycerin. One of the reasons that nitroglycerin can eventually be harmful to the heart is that it destroys an enzyme called ALDH2. This enzyme is responsible for converting nitroglycerin to nitric oxide, the compound that dilates blood vessels and increases blood flow. So by destroying the enzyme, nitroglycerin is dampening the very process in which it plays its helpful rule.
Summing up her results, Mochly-Rosen said, “Basically it’s a cautionary tale... what we found is that if you use [nitroglycerin] for too long, the enzyme that helps protect against tissue damage — ALDH2 — dies. With our animal model, we demonstrated that the loss of this enzyme makes the outcome from the heart attack worse. Nitroglycerin is not benign.” On the other hand, said Mochly-Rosen, “if we had Alda-1 on board, we protected them.”
It’s strange that a practice that’s been around for so long can still present mysteries to researchers. But, as the study shows, learning more about these processes can lead to effective remedies. Hopefully clinicians will take this research into account in the future, as they administer treatments to people who have suffered chest pains or heart attack.
The research was published in the November 2, 2011 issue of Science Translational Medicine, and carried out at Stanford University.