Noninvasive optical cytochrome c oxidase redox state measurements using diffuse optical spectroscopy.
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.
University of California Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612.
Jangwoen
J
Lee
University of California Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612bGwangju Institute of Science and Technology, School of Information and Communications, Department of Medical System Engin.
Jae G
JG
Kim
University of California Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612.
Sari B
SB
Mahon
University of California Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612.
David
D
Mukai
University of California Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612.
David
D
Yoon
University of California San Diego, Department of Medicine, 9500 Gilman Dr., La Jolla, California 92093.
Gerry R
GR
Boss
University of Minnesota, Department of Pharmacology, 516 Delaware Street SE, Minneapolis, Minnesota 55455.
Steven E
SE
Patterson
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010.
Gary
G
Rockwood
Purdue University, Department of Medicinal Chemistry and Molecular Pharmacology, 575 Stadium Mall Drive, West Lafayette, Indiana 47907.
Gary
G
Isom
University of California Irvine, Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Road East, Irvine, California 92612gUniversity of California Irvine Medical Center, Department of Pulmonary and Critical Care, 333 West City Boulevard, Suite.
Matthew
M
Brenner
D000818:Animals; D003576:Electron Transport Complex IV / Q000737:chemistry*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000032:analysis / Q000737:chemistry; D006470:Hemorrhage / Q000503:physiopathology; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000032:analysis / Q000737:chemistry; D011817:Rabbits; D012966:Sodium Cyanide / Q000633:toxicity; D013057:Spectrum Analysis / Q000379:methods*
D006454:Hemoglobins; D010108:Oxyhemoglobins; C100003:deoxyhemoglobin; D003576:Electron Transport Complex IV; D012966:Sodium Cyanide