Research ArticleCardiovascular Disease

ALDH2 Activator Inhibits Increased Myocardial Infarction Injury by Nitroglycerin Tolerance

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Science Translational Medicine  02 Nov 2011:
Vol. 3, Issue 107, pp. 107ra111
DOI: 10.1126/scitranslmed.3002067

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Damping the Dynamite in Nitroglycerin

As a component of dynamite, nitroglycerin’s job is to destroy. As a commonly used drug, this vasodilation-inducing agent is profoundly healing and is often prescribed to alleviate angina—chest pain that arises from arteries narrowed by cardiovascular disease. Now, Sun et al. show that this drug’s destructive nature may rear its ugly head in when used to treat patients with acute myocardial infarction.

In rats, continuous treatment with nitroglycerin for 16 hours before a myocardial infarction increased cardiac damage and diminished cardiac function. These detrimental effects of nitroglycerin resulted from ischemia-induced aldehydic adduct formation, likely because nitroglycerin inhibits ALDH2, a key enzyme that clears these toxic aldehydes. The nitroglycerin-induced heart pathology in the rats was inhibited when the drug was administered with Alda-1, which activates ALDH2. Another drug used to treat angina, isosorbide dinitrate, which does not modulate ALDH2 function, shows no exacerbation of the damage caused by a myocardial infarction. Ultimately, controlled clinical trials will determine the net benefit of nitroglycerin and test whether these findings from animal studies apply in humans. If they do, clinicians may want to reconsider the use of prolonged nitroglycerin treatment in patients likely to experience a myocardial infarction. Alternatively, the addition of ALDH2 activators such as Alda-1 to nitroglycerin regimens could protect patients against these negative effects of nitroglycerin, while preserving its healing benefits.

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