Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells in Pediatric Septic Shock*. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Weiss, Scott L.; Selak, Mary A.; Tuluc, Florin; Perales Villarroel, Jose; Nadkarni, Vinay M.; Deutschman, Clifford S.; Becker, Lance B.
• Is Part Of: Pediatric critical care medicine. Volume 16:Issue 1(2015)
• Publication Date: 2015-01
• Subjects: Pediatric intensive care -- Periodicals; Pediatric emergencies -- Periodicals; 618.05
• DOI: 10.1097/PCC.0000000000000277
• Languages: English
• ISSNs: 1529-7535

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objectives:</title> <p>Mitochondrial dysfunction in peripheral blood mononuclear cells has been linked to immune dysregulation and organ failure in adult sepsis, but pediatric data are limited. We hypothesized that pediatric septic shock patients exhibit mitochondrial dysfunction within peripheral blood mononuclear cells which in turn correlates with global organ injury.</p> </sec> <sec> <title>Design:</title> <p>Prospective observational study.</p> </sec> <sec> <title>Setting:</title> <p>Academic PICU.</p> </sec> <sec> <title>Patients:</title> <p>Thirteen pediatric patients with septic shock and greater than or equal to two organ failures and 11 PICU controls without sepsis or organ failure.</p> </sec> <sec> <title>Interventions:</title> <p>Ex vivo measurements of mitochondrial oxygen consumption and membrane potential (ΔΨ<sub>m</sub>) were performed in intact peripheral blood mononuclear cells on day 1–2 and day 5–7 of septic illness and in controls. The Pediatric Logistic Organ Dysfunction score, inotrope score, and organ failure–free days were determined from medical records.</p> </sec> <sec> <title>Measurements and Main Results:</title> <p>Spare respiratory capacity, an index of bioenergetic reserve, was lower in septic peripheral blood mononuclear cells on day 1–2 (median, 1.81; interquartile range, 0.52–2.09 pmol O<sub>2</sub>/s/10<sup>6</sup> cells) compared with controls (5.55; 2.80–7.21; <italic>p</italic> = 0.03). Spare respiratory capacity normalized by day 5–7. Patients with sepsis on day 1–2 exhibited a higher ratio of LEAK to maximal respiration than controls (17% vs < 1%; <italic>p</italic> = 0.047) with normalization by day 5–7 (1%; <italic>p</italic> = 0.008), suggesting mitochondrial uncoupling early in sepsis. However, septic peripheral blood mononuclear cells exhibited no differences in basal or adenosine triphosphate–linked oxygen consumption or ΔΨ<sub>m</sub>. Oxygen consumption did not correlate with Pediatric Logistic Organ Dysfunction score, inotrope score, or organ failure–free days (all <italic>p</italic> > 0.05). Although there was a weak overall association between ΔΨ<sub>m</sub> on day 1–2 and organ failure–free days (Spearman <italic>ρ</italic> = 0.56, <italic>p</italic> = 0.06), patients with sepsis with normal organ function by day 7 exhibited higher ΔΨ<sub>m</sub> on day 1–2 compared with patients with organ failure for more than 7 days (<italic>p</italic> = 0.04).</p> </sec> <sec> <title>Conclusions:</title> <p>Mitochondrial dysfunction was present in peripheral blood mononuclear cells in pediatric sepsis, evidenced by decreased bioenergetic reserve and increased uncoupling. Mitochondrial membrane potential, but not respiration, was associated with duration of organ injury.</p> </sec> </abstract>