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Chakraborty 2013 Abstracts of ESICM LIVES 2013

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Chakraborty M, Hickey A, Macdonald J, Newby L, Sim D, Phillips A, Windsor J (2013) Evaluation of temporal mitochondrial function in vitro in patients with organ failure: a prospective observational pilot study. Abstracts of ESICM LIVES 2013 S77.

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Chakraborty M, Hickey A, Macdonald J, Newby L, Sim D, Phillips A, Windsor J (2013) Abstracts of ESICM LIVES 2013

Abstract: INTRODUCTION. Septic organ failure is associated with decreased mitochondrial res- piration (MR) 1 , but what happens in multiple organ dysfunction syndrome (MODS) due to other causes is unknown. The decrease in MR is thought to play a significant role in septic organ failure but whether it is causal is not known because temporal MR in sepsis or MODS has never been studied in patients. OBJECTIVES. The primary objective was to measure temporal MR in septic and non septic organ failure (OF) and compare with healthy volunteers (HV, n = 15). The secondary objectives were to assess other mitochondrial function (MF) and correlate MR with sequential organ failure assessment (SOFA). METHODS. After regional ethics approval, patients with OF 2 and: (i) septic shock 2 (S, n = 15) or ii) shock from other causes 2 (NS, n = 11) were prospectively recruited from ICU at Auckland City Hospital. MR, mitochondrial superoxide (SO), and adenine-tri- phosphate (ATP) from peripheral blood mononuclear cells were measured daily during the first week and once at 3 weeks in patients and once from HV. MR was measured with high resolution respirometry using a substrate uncoupler inhibitor titration (SUIT) protocol. Significance was established at P \ 0.05 and a repeated measure ANOVA for temporal MF and ANOVA for comparison with HV were used. RESULTS. The pattern of MR was similar in S and NS over days (P [ 0.05) with decreased oxidative phosphorylation through complex I and II (CI + II OXPHOS) and electron transport system capacity (ET-pathway) compared to HV. In S, CI, II OXPHOS was decreased by 43 % at 4 days (P = 0.002) and by 30 % at 3 weeks (P = 0.03) compared to HV. In NS, CI, II OXPHOS (P = 0.003) was decreased by 49 % at 3 days compared to HV. Additionally, ET capacity was decreased by 23 % at 3 days (P = 0.03) and 25 % at 5/6 days (P = 0.007) compared to HV in S. ATP was decreased by 52 % in S at day 2 and by 45 % in NS at day 3 compared to HV (P \ 0.05 for both). SO increased by 66 and 78 % at day 1 for S and NS respectively and preceded decreases in MR (P \ 0.05 for both). MR correlated with SOFA scores in S and NS from day 3 onwards (d3: r =- 0.651, P = 0.006). CONCLUSIONS. MR dysfunction occurred in S and NS after increases in SO and temporal MR was similar in all OF. MR correlated with severity of MODS from day 3 onwards. Since MR did not decrease until day 3 in S and NS, MR dysfunction is unlikely to be the proximal cause of OF [ACTRN12612000047897


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