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. 2018 Mar;49(3):345-351.
doi: 10.1097/SHK.0000000000000933.

Whole Blood Redox Potential Correlates With Progressive Accumulation of Oxygen Debt and Acts as A Marker of Resuscitation in A Swine Hemorrhagic Shock Model

Rodney C Daniels  1   2 , Hyesun Jun  1   2 , Hakam Tiba  2   3 , Brendan McCracken  2   3 , Pilar Herrera-Fierro  4 , Maryanne Collinson  5 , Kevin R Ward  2   3
Affiliations

Whole Blood Redox Potential Correlates With Progressive Accumulation of Oxygen Debt and Acts as A Marker of Resuscitation in A Swine Hemorrhagic Shock Model

Rodney C Daniels et al. Shock. 2018 Mar.

Abstract

Introduction: Oxidation-reduction reactions involve electron exchanges that require optimal balance for proper cell function. This balance is measured via redox potential and reflects oxidative stress. Despite the critical role of oxidative stress in critical illness and injury, little is known regarding redox potential. We hypothesize redox potential measurements will correlate with accumulation of O2 debt produced by hemorrhage over time.

Methods: Ten swine were studied using a polytrauma hemorrhagic shock model. Whole blood and plasma redox potential measures were obtained at defined stages of O2 debt (20 mL/kg, 40 mL/kg, 60 mL/kg, 80 mL/kg), and through resuscitation. Redox potential was determined by measuring open circuit potential using novel gold nanoporous electrodes with Ag/AgCl reference.

Results: Whole blood redox potential showed negative change as O2 debt accumulated, exhibiting positive response during resuscitation, and correlated with O2 debt across all animals (P < 0.001). Redox potential changes throughout O2 debt accrual were significant compared with baseline (P≤0.05), and at end resuscitation compared with O2 debt 60 mL/kg (P = 0.05) and 80 mL/kg (P = 0.02). Whole blood redox potential measures also correlated with oxygen extraction ratio, ScvO2, and lactic acid, appearing very sensitive to acute changes. Plasma redox potential showed no correlation with O2 debt.

Conclusions: Whole blood redox potential demonstrates significant correlation to O2 debt at all stages in this model. These results set the stage for further study of redox potential as a direct measure of oxidative stress and potential clinical tool. Given redox potential plasma performance, these measures should be made in whole blood versus plasma.

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Conflict of interest statement

Conflicts of Interest: There are no financial relationships to disclose. Authors Daniels, Collinson, and Ward have filed a provisional patent for the redox potential monitoring technology described in this paper through the University of Michigan.

Figures

Figure 1
Figure 1
Scanning Electron Microscopy of the Nanoporous Gold matrix prodced after dealloying gold leaf.
Figure 2
Figure 2
Plot of mean redox potential ±SEM measured in whole blood at matched time points across 10 animals throughout swine traumatic hemorrhagic shock and resuscitation. Samples were tested from each animal at baseline, through O2 Debt accrual (at O2 Debt 20, 40, 60, and 80), at end of resuscitation (ER), and post resuscitation at 30 and 60 minutes (PR30 and PR60). Whole blood redox potential was found to have significant overall correlation with O2 Debt throughout shock and resuscitation when evaluated among all animals in a mixed effects regression analysis (p=0.0016). In addition, redox potential changes throughout O2 debt accrual (at O2 Debt 20, 40, 60, and 80mL/kg) were found to be significant (*) compared to baseline measures (p≤0.012) with redox potential at end resuscitation (ER) showing a significant positive response (#) compared to redox potentials at O2 Debt 60 and O2 Debt 80 (p=0.05 and p=0.02).
Figure 3
Figure 3
Mean redox potential ± SEM measured in plasma at matched time points across 5 animals during swine hemorrhagic/traumatic shock for each point of collection among the animals. Plasma redox potential was found to have no significant correlation with O2 Debt when compared among all animas in a mixed effects regression analysis (p=0.74). In addition, redox potential changes throughout O2 debt accrual (at O2 Debt 20, 40, 60, and 80mL/kg) were found to have no significant change compared to baseline RP measurement (p≥0.48).
Figure 4
Figure 4
Redox potential measured in triplicate (3 separate electrodes, SD ≤ 0.58mV) at matched time points in whole blood (solid line) vs plasma (dashed) in a single representative animal from the swine traumatic shock cohort. Measurements were taken at progressive stages of shock (Baseline; O2 Debt 20, 40, 60, and 80), at End of Resuscitation (ER) and post resuscitation (PR) at 30 and 60 minutes. Note appropriate redox trends in whole blood through shock and with resuscitation, while there is lack of overall variability and no apparent reflection of O2 debt changes or resuscitation in plasma redox potential.
Figure 5
Figure 5
Whole blood redox potential plotted with Oxygen Extraction Ratio (O2ER) as measured throughout shock and resuscitation among all animals studied (n=10). Whole blood redox potential shows a near mirror image response to O2ER among animals with significant correlation between whole blood redox potential measures and calculated O2ER in mixed effects regression analysis (p=0.012). Data shown as mean ± SEM at each time point.
Figure 6
Figure 6
Whole blood redox potential plotted with Lactic Acid (LA) as measured throughout shock and resuscitation among all animals studied (n=10). While redox potential was found to correlate with LA (p=0.005) in our mixed effects regression analysis, redox potential demonstrated real-time response to resuscitation, with positive change over this period (mid resuscitation point is noted by vertical dotted line), while LA continues to rise, peaking sometime after resuscitation before beginning to decline. Data shown as mean ± SEM at each time point.
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