Redox status of cytochrome a,a3: A noninvasive indicator of dysoxia in regional hypoxic or ischemic hypoxia

Objective: Multiwavelength 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 ((V) over dot O-2) when oxygen delivery ((D) over dot O-2) was progressively lowered in an in situ vascularly isolated hindlimb. Design: Prospective, randomized, laboratory study. Setting: University research laboratory. Subjects: Fourteen pigs. Interventions: Measurement of critical values for both (V) over dot O-2 and cyt a,a3 oxidation during ischemic and hypoxic hypoxia. Measurements and Main Results: The right hindlimb of anesthetized, paralyzed, and ventilated pigs was subjected to progressive ischemic or hypoxic hypoxia for 100 mins by ten stepwise decreases in (D) over dot O-2. In ischemic hypoxia(n = 7), arterial inflow ((Q) over dot) from a pump-membrane oxygenator system was lowered from 50 to 0 mL/min, with Pao(2) maintained at 100 mm Hg. in hypoxic hypoxia (n = 6), Pao(2) was lowered from 100 mm Hg to 0 mm Hg. Hindlimb (D) over dot O-2 was calculated as the product of (Q) over dot and arterial oxygen content, and (V) over dot O-2 as the product-of (Q) over dot and arteriovenous :difference. The cyt a,a3 oxidation level was measured every 10 sees with a four-wavelength spectrophotometer. These parameters were measured 9 mins after each change of (D) over dot O-2. critical values for both (V) over dot O-2 and cyt a,a3 oxidation level as a function of (D) over dot O-2 were 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 (V) over dot O-2 in both ischemic and hypoxic hypoxia (r(2) = .90 and .87, respectively). Hindlimb vascular resistance increased in ischemic hypoxia and decreased in hypoxic hypoxia when (D) over dot O-2 reached critical (D) over dot O-2. Conclusions: From 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.