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CLINICAL STUDY

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

Manuscript received January 23, 2001; revised manuscript received July 10, 2001, accepted August 9, 2001.

^* Reprint requests and correspondence: Dr. Kelvin Tsai, Oxidative Stress Clinical Research Group and Division of Critical Care, Department of Medicine, Taipei Veterans General Hospital, 2F, 201, Section 2, Shih-Pai Rd., Taipei, 112, Taiwan
kctsai{at}vghtpe.gov.tw

OBJECTIVES

The purpose of this study was to examine the changes in leukocyte mitochondrial transmembrane potential (MTP) and its association with apoptosis in congestive heart failure (CHF).

BACKGROUND

Congestive heart failure is a heterogeneous syndrome with multiple hemodynamic, neuroendocrine and immune abnormalities. Although edematous CHF may be associated with endotoxemia and increased cytokine production, peripheral blood leukocyte functions in advanced CHF remain unclear.

METHODS

Thirty patients with acute decompensated CHF (mean age [± SEM] 74.9 ± 3.1 years) and 20 healthy controls underwent determination of MTP, intracellular oxidants and apoptosis in three subsets of peripheral blood leukocytes. The measurements were repeated after the time of recompensation.

RESULTS

Patients with acute CHF showed marked MTP reduction and increased intracellular oxidant formation in three subsets of leukocytes upon entry into the study. These changes were more prominent in patients with peripheral edema. The decline in MTP was correlated with the severity of the peripheral edema and plasma concentration of cortisol, nitrogen metabolites and tumor necrosis factor-alpha (p < 0.01). After clinical stabilization, MTP gradually recovered. Leukocytes underwent increased propensity of apoptosis one week after the time of recompensation.

CONCLUSIONS

The mitochondrial depolarization and apoptosis of leukocytes in decompensated heart failure suggest that CHF is associated with severity-dependent impairments in leukocyte function. Accentuated hormonal and cytokine abnormalities and increased circulating oxidants may contribute to these changes. Early and aggressive management of advanced heart failure is helpful in the recovery of these immune abnormalities.

Abbreviations and Acronyms   CHF = congestive heart failure   DCF = 2',7'-dichlorofluorescein   JC-1 = 5,5',6,6'-tetrachloro-1,1'3,3'-tetraethylbenzimidazolcarbocyanine iodide   MTP = mitochondrial transmembrane potential   PBMC = peripheral blood mononuclear cells   PMN = polymorphonuclear leukocytes   PT = permeability transition   TNF = tumor necrosis factor

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