ObjectiveMultiwavelength near infrared (NIR) spectrophotometry can monitor the redox state of cytochrome a,a3 (cyt a,a3) in vivo. Because cyt a,a3 is the most immediate reductant of oxygen, this technique has been proposed to evaluate tissue oxygenation. The purpose of this study was to examine the relationship between cyt a,a3 oxidation level as an indicator of dysoxia and oxygen uptake (VO2) when oxygen delivery (DO2) was progressively lowered in an in situ vascularly isolated hindlimb.DesignProspective, randomized, laboratory study.SettingUniversity research laboratory.SubjectsFourteen pigs.InterventionsMeasurement of critical values for both VO2and cyt a,a3 oxidation during ischemic and hypoxic hypoxia.Measurements and Main ResultsThe right hindlimb of anesthetized, paralyzed, and ventilated pigs was subjected to progressive ischemic or hypoxic hypoxia for 100 mins by ten stepwise decreases in DO2. In ischemic hypoxia (n = 7), arterial inflow (Q) from a pump-membrane oxygenator system was lowered from 50 to 0 mL/min, with PaO2maintained at 100 mm Hg. In hypoxic hypoxia (n = 6), PaO2was lowered from 100 mm Hg to 0 mm Hg. Hindlimb DO2was calculated as the product of Q and arterial oxygen content, and VO2as the product of Q and arteriovenous difference. The cyt a,a3 oxidation level was measured every 10 secs with a four-wavelength spectrophotometer. These parameters were measured 9 mins after each change of DO (2). Critical values for both VO2and cyt a,a3 oxidation level as a function of DO2were determined in each animal by dual linear regression analysis. In ischemic and hypoxic hypoxia, a strong correlation was found between cyt a,a3 oxidation level and VO2in both ischemic and hypoxic hypoxia (r2= .90 and .87, respectively). Hindlimb vascular resistance increased in ischemic hypoxia and decreased in hypoxic hypoxia when DO2reached critical DO2.ConclusionsFrom these results, we concluded that monitoring the cyt a,a3 redox state by NIR spectrophotometry is, in this experimental setting, a sensitive indicator of dysoxia during regional hypoxic or ischemic hypoxia. (Crit Care Med 1999; 27:576-582)