A major need exists for methods to assess organ oxidative metabolic states in vivo. By contrasting the responses to cyanide (CN) poisoning versus hemorrhage in animal models, we demonstrate that diffuse optical spectroscopy (DOS) can detect cytochrome c oxidase (CcO) redox states. Intermittent decreases in inspired O2 from 100% to 21% were applied before, during, and after CN poisoning, hemorrhage, and resuscitation in rabbits. Continuous DOS measurements of total hemoglobin, oxyhemoglobin, deoxyhemoglobin, and oxidized and reduced CcO from muscle were obtained. Rabbit hemorrhage was accomplished with stepwise removal of blood, followed by blood resuscitation. CN treated rabbits received 0.166 mg/ min NaCN infusion. During hemorrhage, CcO redox state became reduced concurrently with decreases in oxyhemoglobin, resulting from reduced tissue oxygen delivery and hypoxia. In contrast, during CN infusion, CcO redox state decreased while oxyhemoglobin concentration increased due to CN binding and reduction of CcO with resultant inhibition of the electron transport chain. Spectral absorption similarities between hemoglobin and CcO make noninvasive spectroscopic distinction of CcO redox states difficult. By contrasting physiological perturbations of CN poisoning versus hemorrhage, we demonstrate that DOS measured CcO redox state changes are decoupled from hemoglobin concentration measurement changes.
Bibliographical noteFunding Information:
The authors acknowledge support by the CounterACT Program, Office of the Director, National Institutes of Health (OD) and the National Institute of Environmental Health Sciences (NIEHS), 1U54NS063718, 1U54NS079201, U01-NS058030, U54-NS079201, AMRMC W81XWH-12-2-0114, Air Force FA9550-04-1-0101, FA9550-08-1-0384, and FA9550-10-1-0438; the NIH/NBIB Laser Microbeam and Medical Program P41-EB015890.
- Cyanide poisoning
- Cytochrome c oxidase
- Diffuse optical spectroscopy
- Physiological perturbation