Tuesday, August 16, 2005

Nitroglycerin: Not for Everyone with Chest Pain?
By Pat French

Nitroglycerin, in addition to being a main component of the explosive TNT, has been used to diagnose and treat angina — chest pain resulting from blocked coronary arteries — since the 1800s. According to a new study, however, it may not benefit everyone with such chest pain.

Jonathan Stamler, MD

In the August 23 issue of the Proceedings of the National Academy of Sciences, Duke investigator Dr. Jonathan Stamler and colleagues show that a specific enzyme is required for this to occur. In their study, mice that lacked a particular enzyme within the mitochondria, aldehyde dehydrogenase or mtALDH, showed no little to no change in blood flow when they were given nitroglycerin, regardless of the dose used. Mice who did possess the enzyme showed the typical drop in blood pressure when nitroglycerin was given, in direct correlation to the dose used.

"Doctors have prescribed nitroglycerin for the relief of chest pain for some 150 years, yet the mechanism by which the drug works has remained a matter of debate," Stamler told dukemednews.org. "The findings confirm that mtALDH is critical for nitroglycerin action."

Given this premise, there appear to be two groups for whom the use of nitroglycerin might be ineffective, or even harmful. The first is the group of people who carry a genetic mutation that results in underproduction of the mtALDH enzyme, which is common in Asian populations. Also possibly affected are people who regularly take drugs that can blunt the action of the enzyme, such as chloral hydrate (a sleeping aid), acetaminophen (Tylenol), sulfonylurea drugs for treating diabetes (DiaBeta, Micronase), and nitrates themselves, if used for long periods. Alcohol also might affect the ability of the enzyme to break down nitroglycerin, the researchers said in the article.

"The results should bring closure to long-standing scientific controversy, and will likely change the way physicians deliver nitroglycerin therapy to patients," said Stamler. "These findings should certainly motivate a reassessment of this class of drugs."

In the future, it might be possible to predict the response of a given person to nitroglycerin treatment via genetic testing. Until then, Stamler warns against the indiscriminate, sustained use of nitroglycerin, especially among patients who may already have mitochondrial damage, such as those with diabetes.

Other authors of the study were Zhiqiang Chen, Matthew Foster, Jian Zhang, Lan Mao, Howard Rockman and Douglas Hess, all from Duke; Toshihiro Kawamoto, of the University of Occupational and Environmental Health in Japan; Kyoko Kitagawa, of Hamamatsu University in Japan; and Keiichi Nakayama, of Kyushu University in Japan.

There was no funding source indicated for the research.