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CLINICAL RESEARCH: MYOCARDIAL ISCHEMIA AND INFARCTION

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

Marco Valgimigli, MD^*,*, Elisa Merli, MD^*, Patrizia Malagutti, MD^*, Olga Soukhomovskaia, MD^*, Giordano Cicchitelli, MD^*, Alessandra Antelli, PhD, Donatella Canistro, PhD, Gloria Francolini, BSc, Gaetano Macrì, MD^*, Francesca Mastrorilli, MD^*, Moreno Paolini, PhD and Roberto Ferrari, MD, PhD^*

^* Chair of Cardiology, University of Ferrara, Ferrara, Italy
Cardiovascular Research Centre, Salvatore Maugeri Foundation, Gussago (Brescia), Italy
Department of Pharmacology, Alma Mater Studiorum, University of Bologna, Bologna, Italy

Manuscript received December 16, 2003; accepted January 7, 2004.

^* Reprint requests and correspondence: Dr. Marco Valgimigli, Chair of Cardiovascular Sciences, University of Ferrara, Cardiovascular Institute, Arcispedale S. Anna Hospital, Corso Giovecca 203, 44100 Ferrara, Italy.
vlgmrc{at}unife.it

OBJECTIVES: We used acetylsalicylic acid (ASA) as a probing agent to quantify hydroxyl radical (^·OH) in Controls and patients with coronary artery disease and to prospectively investigate ^·OH 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 ^·OH 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 ^·OH 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 ^·OH 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.

Abbreviations and Acronyms   ASA = acetylsalicylic acid   DHBA = dihydroxybenzoic acid   HF = heart failure   IL = interleukin   LV = left ventricular   MI = myocardial infarction   ·OH = hydroxyl radical   OSS = oxidative stress status   ROS = reactive oxygen species   SA = salicylic acid   sTNFR = related soluble receptors of tumor necrosis factor-alpha   TNF = tumor necrosis factor

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