Mechanisms of cardiac dysfunction induced by hemorrhagic shock

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Cardiac dysfunction is a well-known complication of hemorrhagic shock as a consequence of local inflammatory response. Several studies have indicated that p38 mitogen-activated protein kinase (MAPK) is a key mediator in organ dysfunction which is associated with the inflammatory state through the activation of proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Whether the same applies to cardiac dysfunction after hemorrhagic shock has not been clearly determined. Therefore, in this study, the role of p38 MAPK on cardiac dysfunction after hemorrhagic shock was studied up to 5 hours after a hemorrhage using FR167653, a specific inhibitor of p38 MAPK phosphorylation. The p38 MAPK phosphorylation, the cardiac mRNA expressions of TNF-α and IL-1β, and intracardiac serum concentrations of each cytokine and CPK-MB increased after a hemorrhage. Activated neutrophil accumulation in the heart, histological inflammation-related injuries and frequent ventricular arrhythmia were observed in the late phase following hemorrhagic shock. FR167653 inhibited these hemorrhagic changes except the induction of the primary hypotensive state. These results demonstrate that p38 MAPK phosphorylation in hemorrhagic shock plays an important role in the cardiac expression of the proinflammatory cytokines, and in the development of cardiac dysfunction relative to the inflammatory responses.