Changes of Nonspecific Proteinases and Proinflammatory Cytokines in the Clinical Course of Acute Myocardial Infarction of Various Severity

Purpose: to study changes of serum levels of nonspecific proteinases, their inhibitors, and proinflammatory cytokines during short term observation of patients with acute myocardial infarction (MI). Materials and Methods. We included in this prospective short-term study 82 patients (27 with uncomplicated non-Qwave MI, 30 with Q-MI complicated by Killip class I-II acute left ventricular failure [ALVF], 17 with Q-MI complicated by Killip class III-IV ALVF, and 8 non-survivors due to development of cardiogenic shock) and 12 healthy controls. Serum levels of interleukin (IL) - 1ß, IL-6 and tumor necrosis factor (TNF)-a were measured by ELISA. Elastase-like (ELA) and trypsin-like (TLA) activities as well as characteristics of proteinase inhibitors (antitrypsin activity and acid-stable inhibitors) were also determined. Blood samples were taken at hospital admission within 24 hours after onset of symptoms. The GUSTO Score at admission was used for risk stratification. Results. All cytokines levels were significantly elevated in MI patients in comparison to controls. Mean concentrations of IL-6 and TNF-a at baseline were higher among patients with MI complicated by ALVF than in the group with uncomplicated MI (27.45 vs 16.04 pikogram/mL, р<0.001, and 24.74 vs 19.58 pikogram/mL, р<0.001, respectively). Mean concentrations of IL-1ß did not differ significantly between these two groups. Non-survivors also showed significantly higher levels of IL-6, TNF-a, ELA and TLA and lower levels of proteinase inhibitors than patients with uncomplicated MI. Conclusions. Elevated levels of IL-6 and TNF-a within 24 hours from the onset of MI are associated with the development of ALVF and unfavorable prognosis. Elevated levels of proteinases and their inhibitors in patients with acute MI are indicative of participation of proteinase-inhibitory system in pathogenesis of MI. Levels of proteinases are significantly elevated in non-survivors compared with patients with uncomplicated MI. On the other hand, low level of proteinase inhibitors should be considered as a marker of imbalance of proteinase-inhibitory system. The data support the role of excessive cytokine-mediated inflammation in worsening of MI course.

инфаркт миокарда, неспецифические протеиназы, ингибиторы неспецифических протеиназ, провоспалительные цитокины, myocardial infarction, nonspecific proteinases, proteinase inhibitors, proinflammatory cytokines

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