Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5′-triphosphate synthase activity
AM Japiassu, APSA Santiago… - Critical care …, 2011 - journals.lww.com
Critical care medicine, 2011•journals.lww.com
Objective: Increasing evidence points to the role of mitochondrial dysfunction in the
pathogenesis of sepsis. Previous data indicate that mitochondrial function is affected in
monocytes from septic patients, but the underlying mechanisms and the impact of these
changes on the patients' outcome are unknown. We aimed to determine the mechanisms
involved in mitochondrial dysfunction in peripheral blood mononuclear cells from patients
with septic shock. Design: A cohort of patients with septic shock to study peripheral blood …
pathogenesis of sepsis. Previous data indicate that mitochondrial function is affected in
monocytes from septic patients, but the underlying mechanisms and the impact of these
changes on the patients' outcome are unknown. We aimed to determine the mechanisms
involved in mitochondrial dysfunction in peripheral blood mononuclear cells from patients
with septic shock. Design: A cohort of patients with septic shock to study peripheral blood …
Abstract
Objective:
Increasing evidence points to the role of mitochondrial dysfunction in the pathogenesis of sepsis. Previous data indicate that mitochondrial function is affected in monocytes from septic patients, but the underlying mechanisms and the impact of these changes on the patients' outcome are unknown. We aimed to determine the mechanisms involved in mitochondrial dysfunction in peripheral blood mononuclear cells from patients with septic shock.
Design:
A cohort of patients with septic shock to study peripheral blood mononuclear cell mitochondrial respiration by high-resolution respirometry analyses and to compare with cells from control subjects.
Setting:
Three intensive care units and an academic research laboratory.
Subjects:
Twenty patients with septic shock and a control group composed of 18 postoperative patients without sepsis or shock.
Interventions:
Ex vivo measurements of mitochondrial oxygen consumption were carried out in digitonin-permeabilized peripheral blood mononuclear cells from 20 patients with septic shock taken during the first 48 hrs after intensive care unit admission as well as in peripheral blood mononuclear cells from control subjects. Clinical parameters such as hospital outcome and sepsis severity were also analyzed and the relationship between these parameters and the oxygen consumption pattern was investigated.
Measurements and Main Results:
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