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

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.