Oxidized Cytochrome Aa3 Research Articles

Simulation and Modelling of near Infrared Spectroscopy (NIRS) as Brain Monitor

Near infrared spectroscopy (NIRS) is a method for non-invasive monitoring of cerebral oxygenation and haemodynamics. Different devices provide information on changes of oxygenated (HbO2) and deoxygenated haemoglobin (HHb), oxidized cytochrome aa3 (CytOx) or regional oxygen saturation (rSO2). NIRS has been used during adult and paediatric cardiac surgery.

Simultaneous Optical Spectroscopic Measurement of Hemoglobin and Myoglobin Saturations and Cytochrome aa3 Oxidation in vivo

A method to simultaneously measure oxygenation in vascular, intracellular, and mitochondrial spaces from optical spectra acquired from muscle has been developed. In order to validate the method, optical spectra in the visible and near-infrared regions (600-850 nm) were acquired from solutions of myoglobin, hemoglobin, and cytochrome oxidase that included Intralipid as a light scatterer. Spectra were also acquired from the rabbit forelimb. Three partial least squares (PLS) analyses were performed on second-derivative spectra, each separately calibrated to myoglobin oxygen saturation, hemoglobin oxygen saturation, or cytochrome aa3 oxidation. The three variables were measured from in vitro and in vivo spectra that contained all three chromophores. In the in vitro studies, measured values of myoglobin saturation, hemoglobin saturation, and cytochrome aa3 oxidation had standard errors of 5.9%, 7.4%, and 12.2%, respectively, with little cross-talk between the in vitro measurements. In the progression from normal oxygenation to ischemia in the rabbit forelimb, hemoglobin desaturated first, followed by myoglobin, while cytochrome aa3 reduction occurred last. The ability to simultaneously measure oxygenations in the vascular, intracellular, and mitochondrial compartments will be valuable in physiological studies of muscle metabolism and in clinical studies when oxygen supply or utilization are compromised.

Intramyocardial oxygen transport by quantitative diffuse reflectance spectroscopy in calves

Intramyocardial oxygen transport was assessed during open-chest surgery in calves by diffuse reflectance spectroscopy using a small intramuscular fiber-optic probe. The sum of hemo- and myoglobin tissue fraction and oxygen saturation, the tissue fraction and oxidation of cytochrome aa3, and the tissue fraction of methemoglobin were estimated using a calibrated empirical light transport model. Increasing the oxygen content in the inhaled gas, 21%-50%-100%, in five calves (group A) gave an increasing oxygen saturation of 19+/-4%, 24+/-5%, and 28+/-8% (p<0.001, ANOVA repeated measures design) and mean tissue fractions of 1.6% (cytochrome aa3) and 1.1% (hemo- and myoglobin). Cardiac arrest in two calves gave an oxygen saturation lower than 5%. In two calves (group B), a left ventricular assistive device (LVAD pump) was implanted. Oxygen saturation in group B animals increased with LVAD pump speed (p<0.001, ANOVA) and with oxygen content in inhaled gas (p<0.001, ANOVA). The cytochrome aa3 oxidation level was above 96% in both group A and group B calves, including the two cases involving cardiac arrest. In conclusion, the estimated tissue fractions and oxygenation/oxidation levels of the myocardial chromophores during respiratory and hemodynamic provocations were in agreement with previously presented results, demonstrating the potential of the method.

Magnetic field effects on near-infrared optical properties of cytochrome oxidase

This paper reports the possible effects of intense magnetic fields on the near-infrared optical properties of cytochrome oxidase. Optical measurements performed on both cytochrome aa3 suspension and in vivo showed changes in optical absorbance at 690–830 nm under magnetic field exposure. Magnetic fields of up to 14 T generated by a superconducting current were able to change the oxidation of the oxidized cytochrome aa3 periodically depending on the density of the magnetic flux. Measurements with a cooled CCD system revealed that the absorbance at 830 nm was slightly increased by a magnetic field of 8 T. We performed an animal experiment on the head of a living rabbit, and obtained results showing the enhancement of cytochrome aa3 oxidation in the mitochondria of cells under the magnetic fields. The effects of magnetic fields on the paramagnetic behavior of oxygen, electron transfer in cytochromes, and cell membrane conformation in mitochondria may playa role in increasing the sensitivity to NIR light for detecting cyto-ox oxidation, which is one of the primary indicators of cellular activity.

The role of graded reoxygenation with cardiopulmonary bypass in prevention of reoxygenation injury and its safety

To investigate the role of graded reoxygenation with cardiopulmonary bypass (CPB) in prevention of reoxygenation injury in children with cyanotic congenital heart defects, and to evaluate its safety. Twenty pediatric patients with cyanotic congenital heart defect were randomly divided into 2 equal groups according to CPB methodology: group 1, undergoing routine hyperoxic CPB with CPB primed and initiated at FiO(2) of 1.0, and group 2 undergoing modified CPB with graded reoxygenation (CPB was primed and initiated at FiO(2) of 0.21 and the FiO(2) was increased slowly to 30% to 60% over the next 5 to 10 minutes). Serum troponin 1 (TnI), S100beta protein, and malondialdehyde (MDA) were measured before CPB, and 1 minute, 5 minutes, and 10 minutes after CPB. Near infrared spectroscopy (NIRS) was applied to evaluate the cerebral oxygenated hemoglobin (HbO(2)) and oxidized cytochrome aa3 (CytOx) and jugular venous lactate was measured during the reoxygenation period. Clinical indexes were observed. Before CPB the TnI, S100beta, and MDA levels in these 2 groups were all normal without significant differences between them. After initiation of CPB the TnI, S100beta, and MDA levels in the two groups began to increase. The serum Tn1 levels 1 minute and 5 minutes after the initiation of CPB of the group 1 were significant lower than those of the group 2 (both P < 0.01). The serum S100beta levels 1, 5, and 10 minutes after the initiation of CPB in the group 2 were all lower than those of the group 1 and there were significant differences between these 2 group 5 and 10 minutes after (both P < 0.05). The serum MDA levels 1, 5, and 10 minutes of the group 1 were significantly higher than those of the group 2 (all P < 0.05). NIRS showed that HbO(2) decreased slightly because of hemodilution when CPB was begun, and then increased rapidly 2 minutes after the initiation of CPB; and CytOx decreased progressively during the reoxygenation period, however, without significant difference between these 2 groups. The serum lactate level was markedly increased 1 minute after the initiation of CPB and then gradually decreased through the reoxygenation period, however, without significant differences between these 2 groups. There was no significant difference between the two groups in clinical observation. Not damaging the cerebral aerobic metabolism, graded reoxygenation with CPB can reduce the extent of reoxygenation injury of routine hyperoxic CPB and is an easy, effective, and safe CPB strategy.

Electrocortical brain activity, cerebral haemodynamics and oxygenation during progressive hypotension in newborn piglets

Objective: To investigate the relationships between systemic and cerebral haemodynamics and oxygenation, and electroencephalogram (EEG) amplitude and frequency analysis studied by the cerebral function analyzing monitor (CFAM) during progressive hypovolemic hypotension. Methods: Six piglets of 1 week of age, weighing 1.9–3.4 kg were mechanically ventilated under 1–1.5% halothane anaesthesia. After 1 h stabilization, blood was withdrawn in aliquots of 10 ml/kg over 15 min up to a total of 40–60 ml/kg. Arterial oxygenation was maintained at normal levels. Thereafter, the total blood volume previously withdrawn, was reinfused. Changes in near infrared spectroscopy (NIRS) parameters [cerebral oxidized cytochrome aa3 (Cytaa3), cerebral blood volume (CBV) or total haemoglobin (tHb: oxy- + deoxyhaemoglobin)], carotid blood flow (Q car), maximal EEG amplitude and EEG frequency percentages were analyzed continuously. Results: The EEG amplitude remained stable until the mean arterial blood pressure (MAP), Q car and tHb dropped below 30 mmHg (41% of baseline), 20 ml/min (33% of baseline) and 82% of baseline, respectively. Delta (δ) wave frequency percentage of the CFAM increased significantly at MAP below 30 mmHg. EEG amplitude remained depressed after blood reinfusion and haemodynamic recovery. Cytaa3 changes were not statistically significant, reflecting sufficient neuronal oxygenation. Conclusion: Our results show that electrocortical function is affected only by profound systemic hypotension. This occurred at a higher level of cerebral oxygen delivery than the level associated with neuronal hypoxia and secondary cell damage.

Pulsatility does not change cerebral oxygenation during cardiopulmonary bypass.

To determine the effect of pulsatility during cardiopulmonary bypass (CPB) on cerebral oxygenation, we measured oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and oxidised cytochrome aa3 (CtO2) with near-infrared spectroscopy (NIRS) in 14 patients electively scheduled for cardiac surgery. Cerebral oxygenation was measured during steady state CPB at a core temperature of 32 degrees C. Non-pulsatile flow and pulsatile flow were performed for 10 min each. After 14 min of CPB, HbO2, Hb and CtO2 were significantly below prebypass values. HbO2 and CtO2 did not alter with changing flow patterns. Hb significantly increased both during the period of nonpulsatile (median: -0.7 vs. 0.25 micromol/l; P<0.05) and pulsatile flow (median: 0.25 vs. 0.5 micromol/l; P<0.001). This increase was independent of flow pattern. Neither oxygenated haemoglobin, nor intracellular oxygenation, represented by CtO2, indicated a beneficial effect of pulsatile perfusion during hypothermic CPB. These results, however, are only valid for short time effects within 10 min before rewarming from CPB and patients without flow-limiting stenoses of the carotid artery.

Effects of endotracheal suctioning in high-frequency oscillatory and conventionally ventilated low birth weight neonates on cerebral hemodynamics observed by near infrared spectroscopy (NIRS).

Adverse changes in cerebral hemodynamics during endotracheal suctioning have been reported in conventionally ventilated newborns, whereas observations on the effect of endotracheal suctioning during high-frequency ventilation have not been reported to date. The present study was designed to investigate the effect of endotracheal suctioning on cerebral hemodynamics in high-frequency and conventionally ventilated infants. Changes in cerebral concentration of oxygenated (cO(2)Hb) and deoxygenated hemoglobin (cHHb) and oxidized cytochrome aa3 (cCyt.aa3) were measured by noninvasive near-infrared spectroscopy. In an open prospective study, 26 suctioning periods in 9 high-frequency and in 6 conventionally ventilated newborn infants were investigated. Heart rate, arterial oxygen saturation (SaO(2)), mean blood pressure (MABP), and transcutaneous carbon dioxide tension (TcpCO(2)) were monitored continuously. In both groups, a marked decrease in heart rate, SaO(2) and in cO(2)Hb, an increase in cHHb, and a variable pattern in the concentration of total hemoglobin were noted during endotracheal suctioning. During suctioning, no statistically significant differences between the two methods of mechanical ventilation could be observed. We conclude that the mode of ventilation had no significant effect on changes in cerebral hemodynamics during endotracheal suctioning.

Effects of decreased cerebral perfusion pressure on cerebral hemodynamics, brain cell membrane function and energy metabolism during the early phase of experimental Escherichia coli meningitis in the newborn piglet.

In this study, we tested the hypothesis that decreased cerebral perfusion pressure (CPP) induces cerebral ischemia and worsen brain damage in neonatal bacterial meningitis. Meningitis was induced by intracisternal injection of 10(9) colony forming units of Escherichia coli in 21 newborn piglets. Although CPP decreased significantly at 8 hr after bacterial inoculation, deduced hemoglobin (HbD), measured as an index of changes in cerebral blood flow by near infrared spectroscopy, did not decrease significantly. In correlation analyses, CPP showed significant positive correlation with brain ATP and inverse correlation with brain lactate levels. CPP also correlated positively with HbD and oxidized cytochrome aa3 (Cyt aa3) by near infrared spectroscopy. However, CPP did not show significant correlation with cerebral cortical cell membrane Na+,K+-ATPase activity, nor with levels of lipid peroxidation products. In summary, decreased CPP observed in this study failed to induce cerebral ischemia and further brain injury, indicating that cerebrovascular autoregulation is intact during the early phase of experimental neonatal bacterial meningitis.

Effects of microbial invasion on cerebral hemodynamics and oxygenation monitored by near infrared spectroscopy in experimental Escherichia coli meningitis in the newborn piglet

This study was carried out to elucidate the pathophysiologic mechanism of cerebral hyperemia observed during the early phase of bacterial meningitis. We tested the hypothesis that microbial invasion through the blood-brain barrier is responsible for cerebral vasodilation and hyperemia in meningitis. Escherichia coli was given either intravenously (i.v.) or intracisternally (i.e.) to closely mimic the primary or secondary bacterial invasion occurring in meningitis and newborn piglets were grouped according to their invasion results (+ or -); 7 2 in the i. v. (+) group, 14 in the i. v.{-) group, 73 in the i. c.( + ) group, 7 5 in the i. c. (-) group. The results were compared with eight animals in the control group. Near infrared spectroscopy (NIRS) was employed to monitor changes in total hemoglobin (HbT), oxygenated hemoglobin (HbO), deoxygenated hemoglobin (Hb), deduced hemoglobin (HbD), and oxidized cytochrome aa3 (Cyt aa3). HbT, as an index of cerebral blood volume, increased progressively in both i.v. (+) and i.v. (-) groups and became significantly different from control and baseline values at 2 h. Hb significantly increased only in i.v. ( + ) group. HbD, as an index of cerebral blood flow, decreased significantly in i.v. ( + ), i.v.(-) and i.e. (-) groups and this change was mitigated in i.e. ( + ) group. HbO was reduced in i.e. (-) group and this decrease was attenuated in i.e. ( + ) group. Increased Cyt aa3 was observed in all experimental groups after bacterial inoculation. Changes in ICP, blood pressure, cerebral perfusion pressure, blood or CSF glucose or lactate, CSF TNF-a level, or CSF leukocytes number were not associated with changes in NIRS findings. These findings suggest that primary or secondary bacterial invasion across the blood-brain barrier is primarily responsible for cerebral vasodilation and hyperemia observed during the early phase of bacterial meningitis. [Neurol Res 1999; 21: 391-398]

The oxygen trail: measurement.

Tissue hypoxia may be defined as abnormal oxygen utilization such that cells are experiencing anaerobic metabolism. Tissue hypoxia can be defined biochemically by low levels of ATP, high levels of NADH, or decreased oxidized cytochrome aa3. It is possible to measure these biochemical markers in the laboratory setting with, for example, nuclear magnetic resonance spectroscopy. However, this is not as yet a clinical option. There is no 'gold standard' for the diagnosis of clinical hypoxia. We can detect the gross consequences of tissue hypoxia, such as organ dysfunction and metabolic markers of anaerobic metabolism (e.g. lactic acidosis). We have also become familiar with the measurement of both global and regional oxygen dispatch and consumption. However, organ dysfunction and metabolic acidosis consistent with established tissue hypoxia commonly exists in the presence of normal and even supra normal global measures of oxygen dispatch and consumption. Therefore, we should ideally make measurements at the end of the oxygen trail, i.e. cellular oxygen delivery and effective utilization.

Near-infrared spectrophotometry of the brain in cardiovascular surgery.

Neuropsychological and neurological deficits are still major causes of mortality and morbidity after cardiac operations and are thought to be caused by embolism and cerebral hypoxia. Near-infrared spectrophotometry (NIRS) is a promising method for non-invasive monitoring of cerebral oxygenation and hemodynamics. Different devices provide information on changes of oxygenated (HbO2) and deoxygenated hemoglobin (Hb), oxidized cytochrome aa3 (CytOx) or regional oxygen saturation (rSO2). NIRS has been applied to patients during adult and pediatric cardiovascular surgery with and without deep hypothermic circulatory arrest (DHCA). In most of the studies, significant changes in cerebral oxygenation were detected by NIRS. NIRS measurements were influenced by the cerebral oxygen metabolism and the operative management. However, clinical, experimental, and theoretical issues raise doubts as to the clinical relevance of the hemoglobin saturation (HbO2, Hb, rSO2 signals) during hypothermia and alkalosis, because the oxygen affinity of hemoglobin increases and a high saturation might simply reflect the inadequate oxygen transport into cells. In contrast, recent experiments have proved a high correlation between the CytOx signal and the MRS parameters nucleoside triphosphate and phosphocreatine. Histological damage was significantly related to the lowest CytOx value; in a clinical study it predicted impaired neuropsychological outcome. Therefore, the CytOx signal is of great interest for future studies. NIRS must prove its ability to diagnose cerebral hypoxia consistently during cardiac surgery in a large patient study before this method is brought into routine clinical practice. Absolute quantification and definitions of critical oxygenation margins will be helpful for this goal.

Spectral and Cyanide Binding Properties of the Cytochrome aa3(600 nm) Complex fromBacillus subtilis

The cytochrome aa3(600 nm) complex, or menaquinol oxidase, fromBacillus subtilisis a member of the cytochrome oxidase superfamily of respiratory membrane protein complexes. We have characterized some spectral properties of this enzyme and its reaction with cyanide. The magnetic circular dichroism (MCD) spectrum of the oxidized enzyme has a single band at 1560 nm in the near-infrared region assigned to bis-histidine-ligated, low-spin ferricytochrome a. The other heme, cytochrome a3, is presumably high-spin in the oxidized enzyme, as isolated. The absence of a trough in the MCD spectrum at 790 nm, observed previously with mammalian cytochrome c oxidase and assigned to CuA(Greenwoodet al., Biochem. J.215, 303–316, 1983), is consistent with the absence of this center from the menaquinol oxidase. When the heme ligand cyanide is added to oxidized menaquinol oxidase, a new MCD band appears at 2010 nm, while the band at 1560 nm is unperturbed. The new band is assigned to low-spin ferricytochrome a3bound with cyanide. The long-wavelength position of this cyanide-induced band is proposed to arise from the close interaction of cytochrome a3with the copper atom, CuB. The kinetics of cyanide binding to oxidized cytochrome aa3(600 nm) reveal a spectrally simple, yet kinetically complex process. The reaction is biphasic with second-order rate constants of 45 and 0.61 M−1s−1at 1 mM KCN, with each phase constituting about 50% of the overall reaction. When the enzyme is subjected to a cycle of anaerobic reduction and air oxidation, the subsequent reaction with cyanide occurs in a single phase at the faster rate. This behavior is ascribed to different conformations of the binuclear center exhibiting different reactivities with cyanide, and is in keeping with that previously established for the structurally more complex mitochondrial cytochrome c oxidase. However, the electronic spectral characteristics of some of the species involved in these reactions are different in the present bacterial case from those of reported eukaryotic systems.

Measurement of Peripheral Venous Oxygen Saturation in the Leg Using Near-Infrared Spectroscopy

Background: It has been suggested that poor healing of wounds may be associated with reduced tissue oxygenation. A non-invasive method of assessing peripheral venous oxygenation has been investigated. Method: Changes in oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), oxidized cytochrome aa3 (cyt aa3) and total haemoglobin (tHb) were monitored in the left lower leg of seven healthy volunteers. A short period of venous occlusion was achieved by rapidly inflating a sphygmomanometer cuff placed around the leg to 60 mmHg. The changes in O2Hb and tHb, with respect to the baseline readings, were evaluated. PSvO2 was calculated from (ΔO2Hb/ΔtHb) × 100%. Results: From 17 sets of readings on the seven volunteers the median PSvO2 calculated was 64% (range 50–86%). Conclusion: This method appears to be a simple means of evaluating PSvO2. A change in cyt aa3 was often seen associated with the venous occlusion.

Near-Infrared Spectroscopy Demonstrates Changes In Cerebral Blood Volume, Oxygenation, And Metabolism In Premature Neonates During Bolus Gavage Feeding† 974

Objective: To determine whether bolus gavage feeding (GF) causes changes in the cerebral vascular or metabolic status of premature neonates detectable by Near-Infrared Spectroscopy (NIRS). Background: Although GF is a routine neonatal practice, its effect on the premature infant's brain is unknown. NIRS is a safe, portable, noninvasive technique which monitors cerebrovascular and metabolic status by determining changes in cerebral concentrations of oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), total hemoglobin (THb) and oxidized cytochrome aa3 (cytaa3). THb is an index of cerebral blood volume and cytaa3 is the terminal electron acceptor in the mitochondrial respiratory chain whose redox status reflects cerebral metabolism. Methods: Fourteen premature infants (24-32 wk GA) receiving intermittent GF were studied 20 min before and up to 1h following a GF. NIRS and systemic parameters (SaO2, HR, RR) were monitored and recorded throughout the study. Eight infants were fed by intermittently passed orogastric tube (OGT) and six were fed by indwelling OGT. Changes in NIRS parameters were determined during OGT insertion and after bolus feed relative to pre-GF values. Data were analyzed during OGT insertion and during defined 5 min intervals following feeding, and analyzed by ANOVA for repeated measures, p<0.05. Results: OGT insertion decreased cerebral HbO and cytaa3 in 6/8 infants. THb was also decreased in 4/6 of these infants. Within 20 min of the feed infusion, THb decreased from baseline in 11/14 infants. In 8/11 of these infants, HbO and HbR were also decreased. Conclusions: Cerebral HbO and cytaa3 decreased during OGT insertion. In infants in whom THb also decreased during OGT insertion, changes in HbO and cytaa3 may be related to diminished cerebral blood flow. Decreased THb, HbO, and HbR after bolus feeds suggest that cerebral blood flow may decrease due to spanchnic steal. These findings highlight the cerebrovascular and metabolic reactivity of premature infants during routine nursery procedures. These changes in cerebral circulation and metabolism are detectable by NIRS but are not clinically evident or detected by routine monitoring. The significance of these changes in the preterm infant's brain is unknown and warrants further study.

Pulse oximetry — physiological considerations

Fetal well-being depends on the level of oxygenation in vital organs such as the heart and brain. In this review, we discuss the physiological parameters which underlie the use of pulse oximetry to evaluate fetal conditions intrapartum. Whilst the measurement of haemoglobin oxygen saturation (Sao2) depends on partial pressure of oxygen (Po2), the relation is alinear, is relatively insensitive to changes in Po2 at the upper physiological range, and it is affected by the Bohr shift. Oxygen content of the blood cannot be determined without measurement of haemoglobin (Hb) content and this can change quite quickly. In hypoxia for example, oxygen delivery to an organ, e.g. the brain, cannot be assessed without simultaneous measurement of blood flow, which again changes with fetal condition. Lastly, it is not possible to guage fetal tissue unless some measure of, for example, cytochrome aa3 oxidation is used: tissue oxidation in relation to oxygen delivery can change due to local vascular readjustments and changes in metabolism. We conclude that use of Sao2 to assess fetal well-being is fraught with difficulties, and that much more research is needed before its routine clinical use can be considered.© 1997 Elsevier Science Ireland Ltd.

Multichannel analysis of single-turnover kinetics of cytochrome aa3 reduction of O2.

The single-turnover kinetics of the oxidation of cytochrome aa3 by O2 have been studied using a new approach. Up to 1000 whole spectra covering both the Soret and alpha regions were sequentially collected at room temperature from single samples with a time resolution of 10 microns. All of the spectral and time information were used in analyses based on singular value decomposition. Four spectral transitions (i.e., intermediates) were distinguished with time constants near 0.01, 0.1, 1.1, and 30 ms. Two different kinds of sequential models were evaluated, one linear and the other branched. Although past kinetic analyses have emphasized the linear sequential model, the complexity of the intramolecular electron transfer in this enzyme suggests that a branched model be considered. This is especially true in a single-turnover experiment where earlier optical and EPR studies have pointed unequivocally to a branched model [Clore et al. (1980) Biochem. J. 185, 139-154; Blair et al. (1985) J. Am. Chem. Soc. 107, 7389-7399]. In the present study, analysis of spectral data in terms of the linear model did not reveal the formation and decay of the expected oxyferryl intermediate, whereas analysis of the branched model did. The results obtained using the branched model are consistent with all of the available evidence from a broad range of physical techniques that have been applied to examine the single-turnover kinetics of the oxidation of reduced cytochrome aa3 by O2.

Changes in subcutaneous interstitial fluid pressure, tissue oxygenation, and skin red cell flux during venous congestion plethysmography in men.

Venous congestion plethysmography enables noninvasive assessment of microvascular filtration capacity (Kf) in limbs. However, increases in fluid filtration might alter the balance of Starling forces: for example, progressive increases in interstitial fluid pressure (Pi) would reduce net fluid flux, thus underestimating Kf. Furthermore, elevation of cuff pressure to values close to diastolic blood pressure, as used in the protocol, may be itself impair tissue perfusion with unknown effects on the microvascular parameters investigated. Pi was measured in healthy volunteers (n = 14) with a modified "Wick in needle" technique during small (8 mm Hg) cumulative increases in venous pressure (0-95 mm Hg). Changes in the hemoglobin (Hb) concentration, oxygenated hemoglobin (HbO2) concentration and oxidized cytochrome aa3 concentration were assessed in the calf using noninvasive near-infrared spectroscopy. Skin red blood cell flux close to the strain gauge was evaluated by laser Doppler fluxmetry. Pi at control was -0.89 +/- 0.8 mm Hg and during elevation of venous pressure remained constant until a cuff pressure of 30 mm Hg was reached. It rose thereafter to 1.57 +/- 1.3 mm Hg (mean +/- SD). Skin red cell flux was significantly reduced when cuff pressure exceeded 30 mm Hg and following cuff deflation, evidence of reactive hyperemia was obtained. Hb concentration increased significantly as a result of venous pressure elevation. No change in either HbO2 or cytochrome aa3 concentration was observed as long as cuff pressure remained under diastolic blood pressure. The small increase in Pi together with an absence of impaired tissue oxygenation during the venous congestion plethysmography protocol described by Gamble et al. supports the contention that this protocol enables accurate assessment of filtration capacity.

Near-infrared spectroscopy in experimental pneumococcal meningitis in the rabbit: cerebral hemodynamics and metabolism.

Near-infrared spectroscopy is a noninvasive technique which measures oxidized cytochrome aa3, oxygenated Hb, and deoxygenated Hb and calculates total Hb in tissue. This technique, in conjunction with measurement of cerebral blood flow, was used in rabbits with experimental bacterial meningitis to determine whether there was evidence for cerebral energy depletion and alterations in the cerebral vascular bed with infection. Rabbits with meningitis had a significant reduction in cerebral blood flow, cerebral oxidized cytochrome aa3 and a relative increase in the deoxygenated Hb fraction and a decrease in the oxygenated Hb fraction compared with uninfected controls. Total Hb was not significantly different between the two groups. These findings may help clarify the mechanism for some of the intracranial pathophysiologic abnormalities in meningitis.

Cytochrome aa3 -signal changes in newborn piglets during hypoxia. 38

Background: The aim was to study changes in cerebral oxidized cytochrome aa3 (cytaa3) with near-infrared spectrophotometry (NIRS) during stepwise hypoxia.