Translational Application of Measuring Mitochondrial Functions in Blood Cells Obtained from Patients with Acute Poisoning
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It is conservatively estimated that 5,000 deaths per year and 20,000 injuries in the USA are due to poisonings caused by chemical exposures (e.g., carbon monoxide, cyanide, hydrogen sulfide, phosphides) that are cellular inhibitors. These chemical agents result in mitochondrial inhibition resulting in cardiac arrest and/or shock. These cellular inhibitors have multi-organ effects, but cardiovascular collapse is the primary cause of death marked by hypotension, lactic acidosis, and cardiac arrest. The mitochondria play a central role in cellular metabolism where oxygen consumption through the electron transport system is tightly coupled to ATP production and regulated by metabolic demands. There has been increasing use of human blood cells such as peripheral blood mononuclear cells and platelets, as surrogate markers of mitochondrial function in organs due to acute care illnesses. We demonstrate the clinical applicability of measuring mitochondrial bioenergetic and dynamic function in blood cells obtained from patients with acute poisoning using carbon monoxide poisoning as an illustration of our technique. Our methods have potential application to guide therapy and gauge severity of disease in poisoning related to cellular inhibitors of public health concern.
KeywordsMitochondria Respiration Motility Carbon monoxide Toxicology Poisoning
Sources of Funding
This work was funded by NIH grant K08HL136858 and the American College of Medical Toxicology (ACMT)-Medical Toxicology Foundation Research and Teaching Award (DJ) and Office of Naval Research grants N000141612100 and N000141712643 (DME).
Compliance with Ethical Standards
The University of Pennsylvania Institutional Review Board approved this study and informed consent was obtained from the patient or an appropriate surrogate.
Conflicts of Interest
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