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P Menager

Publications and source records attributed to P Menager.

4 recordsLinked to original sources
PubMed1999

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 (VO2) when oxygen delivery (DO2) 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 VO2 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 DO2. In ischemic hypoxia (n = 7), arterial inflow (Q) from a pump-membrane oxygenator system was lowered from 50 to 0 mL/min, with PaO2 maintained at 100 mm Hg. In hypoxic hypoxia (n = 6), PaO2 was lowered from 100 mm Hg to 0 mm Hg. Hindlimb DO2 was calculated as the product of Q and arterial oxygen content, and VO2 as 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 DO2. Critical values for both VO2 and cyt a,a3 oxidation level as a function of DO2 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 VO2 in both ischemic and hypoxic hypoxia (r2 =.90 and .87, respectively). Hindlimb vascular resistance increased in ischemic hypoxia and decreased in hypoxic hypoxia when DO2 reached critical DO2. 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.

Animals↗
PubMed1995

ATP-sensitive K+ channel blockade impairs O2 extraction during progressive ischemia in pig hindlimb.

Tissues maintain O2 consumption (VO2) when blood flow and O2 delivery (DO2) are decreased by better matching of blood flow to meet local cellular O2 demand, a process that increases extraction of available O2. This study tested the hypothesis that ATP-sensitive K+ channels play a significant role in the response of pig hindlimb to ischemia. We pump perfused the vascularly isolated but innervated right hindlimb of 14 anesthetized pigs with normoxic blood while measuring hindlimb DO2, VO2, perfusion pressure, and cytochrome aa3 redox state. In one-half of the pigs, the pump-perfused hindlimb was also infused with 10 micrograms.min-1.kg-1 of glibenclamide, a potent blocker of ATP-sensitive K+ channels. Control animals were infused with 5% glucose solution alone. Blood flow was then progressively reduced in both groups in 10 steps at 10-min intervals. Glibenclamide had no effect on any preischemic hindlimb or systemic measurements. Hindlimb VO2 and cytochrome aa3 redox state began to decrease at a significantly higher DO2 in glibenclamide-treated compared with control pigs. At this critical DO2, the O2 extraction ratio (VO2/DO2) was 53 +/- 4% in the glibenclamide group and 73 +/- 5% in the control group (P < 0.05). Hindlimb vascular resistance increased significantly with ischemia in the glibenclamide group but did not change in the control group. We conclude that ATP-sensitive K+ channels may be importantly involved in the vascular recruitment response that tried to meet tissue O2 needs as blood flow was progressively reduced in the pig hindlimb.

Adenosine Triphosphate↗