A preliminary study in the alterations of mitochondrial respiration in patients with carbon monoxide poisoning measured in blood cells

Abstract

Objectives Carbon monoxide (CO) is a colorless and odorless gas that is an important cause of poisoning mortality and morbidity in the United States. At this time there is no reliable method to predict severity of poisoning or clinical prognosis following CO exposure. Whole blood cells such as peripheral blood mononuclear cells (PBMCs) and platelets have been explored for their potential to act as sensitive biomarkers for mitochondrial dysfunction. Design The objective of this study was to measure mitochondrial respiration using intact cells obtained from patients exposed to CO as a potential biomarker for mitochondrial inhibition with results that can be obtained in a time frame useful for guiding clinical care. This was a prospective, observational pilot study performed from July 2015 to July 2016 at a single academic tertiary care center that is the location of the region’s only multi chamber hyperbaric. Measurements Clinical characteristics, patient demographics, mitochondrial respiration and outcomes were recorded. Main results There were 7 patients enrolled with a mean COHb level was (26.8+/−10) with a mean lactate of (1.1+/−0.4 mmol/L). All 7 CO exposures were related to heat generators used during winter months with two deaths. There was a positive correlation between maximal respiration and COHb levels with both a high maximal respiration and high spare respiratory capacity correlating with a high COHb level. There was a subset of PBMCs (n=4) that were analyzed for Complex IV (cytochrome c oxidase) activity. Conclusion In this pilot study, measurement can be performed in an appropriate timeline for clinical care with potential to serve as a prognostic marker. Further work is necessary to develop high-resolution respirometry as a clinical tool for assessing severity of illness and guiding therapy.

Translational Application of Measuring Mitochondrial Functions in Blood Cells Obtained from Patients with Acute Poisoning

“…In the CO group, mitochondrial respiration was significantly lower at key respiratory states that includes complex IV or cytochrome c oxidase respiration with a resultant decrease in other key respiratory states such as Max respiration and uncoupled CI respiration. The finding that CO results in a decrease in CIV respiration with a decrease in other complex activity is a consistent finding in our previous work as well as others [12,25,34,35]. There were no differences in other respiratory states such as uncoupled CII which is most likely related to our sample size where a larger sample size may detect a significant difference [12,25,34,35].…”

“…We performed a specialized protocol to establish the respiratory capacities at various complexes providing more detailed respiratory activity at complex (C) I, II, III, IV. Our published manuscripts describe these methods in further detail in regard to injections with specific concentrations [12,25,28].…”

“…There has been increased use of human blood cells such as peripheral blood mononuclear cells (PBMCs), which contains a mixed population of monocytes and lymphocytes, as surrogate markers of mitochondrial function [19]. The measurement of mitochondrial respiration in PBMCs obtained from subjects with acute care illnesses has been explored [2,[20][21][22][23][24][25]. We have also published a study that now combines the ability to measure mitochondrial networking in human blood cells [26].…”

Mitochondrial dynamics and respiration within cells with increased open pore cytoskeletal meshes

“…This allows measure of H 2 O 2 production and respiration in various control states as described above. ( Jang et al, 2017 ; Krumschnabel et al, 2015 ).…”

Introductory Chapter: Linkages Between Clinical and Forensic Toxicology

“…It should be noted that several types of equipment are required for providing analytical toxicological assessments, this include: a. A carbon monoxide (CO)-Oximeter: normally very necessary for determining carboxyhaemoglobin and methaemoglobin measurements in case of a suspected incident by carbon monoxide [15].…”