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Leukocyte mitochondria depolarization and apoptosis in advanced heart failure: clinical correlations and effect of therapy

Chi-Woon Kong, MD^*, Tai-Ger Hsu, PhD, Fung-Jou Lu, PhD, Wan-Leong Chan, MD, FACC^* and Kelvin Tsai, MD^*,*

^* Oxidative Stress Clinical Research Group and Division of Critical Care, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan
Institute of Sports Science, Taipei Physical Education College, Taipei, Taiwan
Department of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan

View larger version (32K): [in a new window]   Figure 1 Time-sequence changes of mitochondrial transmembrane potential (MTP) (left panel) and intracellular oxidants (right panel) in peripheral blood polymorphonuclear leukocytes (PMN), monocytes and lymphocytes. The MTP was expressed as the ratio of the mean fluorescence intensity of 5,5',6,6'-tetrachloro-1,1'3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) aggregates and JC-1 monomers. Intracellular oxidants were expressed as the mean fluorescent intensity of 2',7'-dichlorofluorescein (DCF). *p < 0.01 compared among different time points; p < 0.01 compared between two congestive heart failure (CHF) groups.

View larger version (20K): [in a new window]   Figure 2 Propensity of apoptosis in polymorphonuclear leukocytes (PMN) (A) and peripheral blood mononuclear cells (PBMC) (B) as determined by flow cytometric TUNEL assay. The percentage of cells with DNA fragmentation of nuclei equals the high fluorescein isothiocyanate-dUTP–labeled population divided by the total cell population. *p < 0.01 compared among different points. A significant (p < 0.01) interaction exists between time variable and group variable in (B).

View larger version (26K): [in a new window]   Figure 3 Time sequence changes of plasma nitrogen metabolites (A), lipid peroxides (B), cortisol (C), tumor necrosis factor (TNF)- (D) and interleukin-6 (E) concentrations. *p < 0.01 compared among different time points; p < 0.01 compared between two congestive heart failure (CHF) groups. A significant (p < 0.01) interaction exists between time variable and group variable in (E).