• Cho-Kai Wu, Eng-Kean Yeong, Heng-Hsu Lin, Fu-Tien Chiang, Yueh-Bih Tang, and Chia-Ti Tsai.
• Department of Traumatology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
• Shock. 2012 May 1;37(5):457-62.

AbstractSevere inflammation leads to cardiac diastolic dysfunction, an independent prognostic marker for the mortality of critically ill patients. We investigated the possible molecular mechanism from inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) causing left ventricular (LV) diastolic dysfunction in critically burned patients. We consecutively enrolled 56 critically burned patients who were admitted to the intensive care unit and performed transthoracic echocardiography to evaluate LV diastolic function. Sarcoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) gene expression in HL-1 cardiomyocytes was used as a molecular phenotype of diastolic heart failure. Soluble plasma levels of TNF-α and IL-6 were measured in all subjects. The effect of serum from the burned patients on SERCA2 gene expression of HL-1 cardiomyocytes was investigated. The total body surface area of burned patients was proportional to serum level of IL-6 and TNF-α (P < 0.001 for each). Significant correlations were found for TNF-α and decelerating time, E/A, and E/Em (r² = 0.59, 0.45, and 0.52; P <0.001 for each) and for IL-6 and decelerating time, E/A, and E/Em (r² = 0.63, 0.60, and 0.62; P < 0.001 for each). Diastolic function improved significantly in association with decrease in cytokines after burned patients were transferred to general ward (P < 0.001). Tumor necrosis factor α, IL-6, and sera from critically burned patients downregulated the expression of the SERCA2 gene in HL-1 cardiomyocytes. There was a significant correlation between LV diastolic dysfunction and in-hospital mortality in critically burned patients (hazard ratio, 3.92; P = 0.034) after risk factors were adjusted. Inflammatory cytokines may be associated with cardiac diastolic, which could be an independent prognostic factor in burn patients. Novel therapeutic strategies may be applied in critically burned patients with LV diastolic dysfunction by modulating inflammatory reactions.

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