Abstract
Background: Sepsis-induced alterations in mitochondrial function contribute to organ dysfunction and mortality. Measuring mitochondrial function in vital organs is neither feasible nor practical, highlighting the need for non-invasive approaches. Mitochondrial function may be reflected in the concentrations of metabolites found in platelets and whole blood (WB) samples. We proposed to use these as alternates to indirectly estimate platelet mitochondrial oxygen consumption rate (mOCR) in sepsis patients. Methods: We determined the relationships between platelet mOCR and metabolites in both platelets and WB, as measured by quantitative 1H-NMR metabolomics. The associations were identified by building multiple linear regression models with stepwise forward-backward variable selection. We considered the models to be significant with an ANOVA test (p-value ≤ 0.05) and a positive predicted-R2. Results: The differences in adjusted-R2 and ANOVA p-values (platelet adj-R2: 0.836 (0.0003), 0.711 (0.0004) vs. WB adj-R2: 0.428 (0.0079)) from the significant models indicate the platelet models were more associated with platelet mOCR. Conclusions: Our data suggest there are groups of metabolites in WB (leucine, acetylcarnitine) and platelets (creatine, ADP, glucose, taurine) that are associated with platelet mOCR. Thus, WB and platelet metabolites could be used to estimate platelet mOCR.
Highlights
Sepsis mortality rates range from 25–30%, and the incidence of sepsis is increasing in the aging population [1,2]
Using multiple linear regression (MLR) models, we identified groups of metabolites in whole blood (WB) and platelets that are associated with platelet mitochondrial oxygen consumption rate (mOCR)
Of the 31 sepsis subjects, 17 had mOCR matched to WB nuclear magnetic resonance (NMR) metabolomics, while 14 had completed mOCR matched to platelet
Summary
Sepsis mortality rates range from 25–30%, and the incidence of sepsis is increasing in the aging population [1,2]. New diagnostic approaches to the assessment of mitochondrial dysfunction are needed. Sepsis-induced alterations in mitochondrial function contribute to organ dysfunction and mortality. Measuring mitochondrial function in vital organs is neither feasible nor practical, highlighting the need for non-invasive approaches. Mitochondrial function may be reflected in the concentrations of metabolites found in platelets and whole blood (WB) samples. We proposed to use these as alternates to indirectly estimate platelet mitochondrial oxygen consumption rate (mOCR). Results: The differences in adjusted-R2 and ANOVA p-values (platelet adj-R2 : 0.836 (0.0003), 0.711 (0.0004) vs WB adj-R2 : 0.428 (0.0079)) from the significant models indicate the platelet models were more associated with platelet mOCR. Conclusions: Our data suggest there are groups of metabolites in WB (leucine, acetylcarnitine) and platelets (creatine, ADP, glucose, taurine) that are associated with platelet mOCR. WB and platelet metabolites could be used to estimate platelet mOCR
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