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In the work the efficacy of influence of cardiotonic drugs on the cytokine system changes in the response to acute maximal myocardial pressure overload in congestive heart failure (HF) animals was study in controlled randomized trial. It has been shown, that treatment with Adenocin unlike levosimendan in HF occurs restoration of systolic and diastolic function not only at rest, but also under the acute maximal pressure overload. Therapy with levosimendan at acute pressure overload condition leads to the additional dysbalance in the proinflammatory cytokines and activation of nuclear factor (NF)-kB, as marker of pivotal role of innate immune system in cardiac remodeling under HF. Beneficial action of adenocin on the restoration the balance between pro- and anti-inflammatory cytokine production associated with the normalization of activation of NF-kB that leads to adequate expression of tumor necrosis factor (TNF)-a and interleukin (IL) 1ß in myocardium. Obtained results suggested the hypothesis about acute response of IL6 and in less extent changes in IL 1ß and TNF-a. Thus, adenocin restores myocardium tolerance to pressure overload and reserve ability of immune system, while levosimendan occurs less harmonized action.