Hydroxyl radical generation, levels of tumor necrosis factor-alpha, and progression to heart failure after acute myocardial infarction Original Research Article

Objectives We used acetylsalicylic acid (ASA) as a probing agent to quantify hydroxyl radical (radical dotOH) in Controls and patients with coronary artery disease and to prospectively investigate radical dotOH production in patients with myocardial infarction (MI) complicated by heart failure (HF). Background Oxidative stress status (OSS) is a mechanism for transition to HF in experimental heart injury models, but evidence for its causal role in humans is still limited. Methods Thirty healthy subjects (Controls), 12 patients with stable angina (Group 1), and 74 patients with ST-segment elevation MI (Group 2) were enrolled. A dose of 250 mg Flectadol was given intravenously before each blood collection to determine the 2,3-dihydroxybenzoic acid/salicylic acid (DHBA/SA) ratio. We also quantified vitamin E and coenzyme Q10 to monitor antioxidant reserve, as well as tumor necrosis factor (TNF)-alpha, TNF-soluble receptors, interleukin (IL)-6, and IL-1ra to assess inflammatory status. All measurements were repeated at month 6 in Group 2. Results There were no differences between Controls and Group 1. Group 2 showed increased radical dotOH production, peaking at 24 h, whereas vitamin E and coenzyme Q10 progressively declined. Group 2 patients developing HF during hospitalization (Group 2Bi) presented with an increase of both radical dotOH production at discharge and inflammatory status, as compared with patients without HF (Group 2Ai), persisting at month 6 in post-MI patients with HF (Group 2Bii). Conclusions We found a distinct pattern of radical dotOH generation in post-MI patients who show progression to HF. The interplay between OSS and inflammatory status should be targeted as a possible mechanism of progression to post-MI left ventricular dysfunction.