Redox State Of Cytochrome Oxidase Research Articles

The influence of carbon dioxide on cerebral metabolism and oxygen consumption: combining multimodal monitoring with dynamic systems modelling.

Hypercapnia increases cerebral blood flow. The effects on cerebral metabolism remain incompletely understood although studies show an oxidation of cytochrome c oxidase, Complex IV of the mitochondrial respiratory chain. Systems modelling was combined with previously published non-invasive measurements of cerebral tissue oxygenation, cerebral blood flow, and cytochrome c oxidase redox state to evaluate any metabolic effects of hypercapnia. Cerebral tissue oxygen saturation and cytochrome oxidase redox state were measured with broadband near infrared spectroscopy and cerebral blood flow velocity with transcranial Doppler ultrasound. Data collected during 5-min hypercapnia in awake human volunteers were analysed using a Fick model to determine changes in brain oxygen consumption and a mathematical model of cerebral hemodynamics and metabolism (BrainSignals) to inform on mechanisms. Either a decrease in metabolic substrate supply or an increase in metabolic demand modelled the cytochrome oxidation in hypercapnia. However, only the decrease in substrate supply explained both the enzyme redox state changes and the Fick-calculated drop in brain oxygen consumption. These modelled outputs are consistent with previous reports of CO2 inhibition of mitochondrial succinate dehydrogenase and isocitrate dehydrogenase. Hypercapnia may have physiologically significant effects suppressing oxidative metabolism in humans and perturbing mitochondrial signalling pathways in health and disease.

Intramuscular administration of hexachloroplatinate reverses cyanide-induced metabolic derangements and counteracts severe cyanide poisoning.

Cyanide is a highly toxic industrial chemical that is widely used by manufactures. Smoke inhalation during household fires is the most common source of cyanide poisoning while additional risks to civilians include industrial accidents and terrorist attacks. Despite the risks to large numbers of individuals, an antidote capable of administration at scale adequate for a mass casualty, prehospital scenario does not yet exist. Previously, we demonstrated that intravenous cisplatin analogues accelerate recovery from cyanide poisoning in mice and rabbits. Of the dozens of platinum‐based organometallic complexes tested, hexachloroplatinate (HCP) emerged as a promising lead compound, exhibiting strong affinity for cyanide and efficacy across model systems. Here, we show HCP is an antidote to lethal cyanide exposure and is importantly effective when delivered intramuscularly. The pharmacokinetic profile of HCP exhibited bioavailability in the systemic circulation 2.5 minutes post‐treatment and subsequent renal clearance of HCP‐cyanide. HCP restored parameters of cellular physiology including cytochrome c oxidase redox state and TCA cycle metabolism. We next validated these findings in a large animal model (swine). Finally, preclinical safety studies in mice revealed minimal toxicity. Cumulatively, these findings demonstrate that HCP is a promising lead compound for development of an intramuscular injectable cyanide antidote for mass casualty scenarios.

S187. Cerebral oxygen saturation and cytochrome oxidase redox state in children with epilepsy: A pilot study - MULTICHANNEL NIRS for epilepsy seizure detection

Epilepsy remains a significant healthcare problem associated with significant morbidity and mortality. Electroencephalograms (EEGs) provide a means of identifying ongoing seizures. However, specialized equipment is needed to obtain and interpret data. There remains a need for technologies that are easily utilized and interpreted for the purpose of monitoring children in the time periods before, during and after seizure activity. NIRS cerebral oximetry works as a noninvasive measurement that allows continuous measurement of cerebral oxygen availability. This monitor serves as a surrogate to invasive measures of venous pO2, often obtained from the jugular vein to estimate cerebral oxygen levels. We recently published NIRS-EEG data with a limited number of NIRS probes in four patients with medically refractory epilepsy undergoing pre-surgical evaluation with ages ranging from 5 to 17 years. The purpose of this pilot study is to describe the relationship of regional cerebral oximetry and cytoximetry, measured using MULTICHANNEL NIRS (near-infrared spectroscopy) in the peri-ictal period in children with epilepsy. The hypothesis is: 1. Regional cerebral saturation of oxygen and/or cytochrome oxidase redox state will increase prior to the onset of seizure activity; 2. Regional cerebral saturation of oxygen and/or cytochrome oxidase redox state will have a varied response during seizure activity depending on the seizure type; 3. Regional cerebral saturation of oxygen and/or cytochrome oxidase redox state will return to baseline following cessation of seizure activity. The three goals for the research study are to: 1. Quantify the magnitude and direction of change of cerebral oxygen saturation and cytochrome oxidase redox state during the peri-ictal period in children with epilepsy; 2. Quantify the temporal relationship, magnitude and direction of change of cerebral oxygenation and cytochrome oxidase redox state in relationship to seizure type; 3. Measure the association of cerebral oxygenation and cytochrome oxidase redox state with systemic oxygen saturation, EEG findings and clinical status. Study subjects will include pediatric patients from birth to 18 years of age with a known seizure disorder who are being admitted to the epilepsy monitoring unit (EMU) or the ICU at CHW for further workup or medication management of their epilepsy. Children will be monitored per standard of care for the duration of their hospitalization, which typically is 3–5 days with the additional NIRS-EEG array added to their monitoring. Preliminary data shows varied regional cerebral oxygen saturation and/or cytochrome oxidase redox state during interictal period and seizure activity depending on the seizure type. The increased blood flow clearly coincided with epileptiform activity and continued to increase as the epileptiform activity built up. Regional cerebral oxygen saturation increased in the epileptogenic focus, perhaps due to loss of cerebrovascular autoregulation.

Effects of Cyclosporine Pretreatment on Tissue Oxygen Levels and Cytochrome Oxidase in Skeletal Muscle Ischemia and Reperfusion

We hypothesized that pretreatment with single-dose cyclosporine (CsA) prevents alterations and improves tissue oxygen and mitochondrial cytochrome oxidase redox (CytOx) state in skeletal muscle ischemia and reperfusion-reoxygenation (I/R). Latissimus dorsi muscle was prepared and mobilized in New Zealand white rabbits. Ischemia was induced for 4 h, followed by 2 h of reperfusion. The animals were randomized to receive a 60-mg/kg intravenous bolus of CsA (CsA group, n = 10) or physiologic saline (control, n = 10) at 10 min before ischemia onset. Muscle tissue oxygen tension (PtO(2)) and mitochondrial CytOx were measured during I/R simultaneously. High-energy phosphate (HEP) levels were determined using high-field (31)P magnetic resonance spectroscopy. Mitochondrial viability index and wet-to-dry ratio were used to assess the tissue viability between groups. Decreases in tissue oxygen levels and CytOx were slower during ischemia in the CsA group in comparison to control group, also the loss of phosphocreatine and adenosine triphosphate depletion. After ischemia, recovery of tissue oxygen, mitochondrial CytOx, and HEP was delayed in controls. Tissue PtO2 in the CsA group (P < 0.05) was significantly higher compared with that in the control group after I/R. Mitochondrial CytOx was also improved in the CsA group (P < 0.01 vs. control). Muscle HEP levels (phosphocreatine, adenosine triphosphate) were significantly preserved in the CsA group versus the control group (P < 0.01, P < 0.05). Mitochondrial viability index and wet-to-dry ratio confirmed significantly preserved tissue and lower edema formation in the CsA group. The pretreatment with single-dose CsA prevents alterations and improves tissue oxygenation and mitochondrial oxidation in skeletal muscle I/R.

22 Tissue Oxygenation in the Light of Non-Invasive and Continuous Near-Infrared Spectroscopy and Imaging (NIRS, NIRI)

Near-infrared spectrophotometry (NIRS) and imaging (NIRI) are quickly growing optical methods to non-invasively and in vivo study oxygenation of human tissue. NIRS and NIRI are appreciated by patients, relatives e.g....

Superoxide production during ischemia–reperfusion in the perfused rat heart: A comparison of two methods of measurement

Reactive oxygen species (ROS) have been implicated in many aspects of tissue/cellular metabolic signaling and pathology, including cardioprotection against ischemia–reperfusion damage. Recent reports of enhanced ROS production under global or simulated ischemia in intact heart or isolated cardiomyocytes, respectively, and its decrease again upon reperfusion are paradoxical. Mechanisms for increasing ROS production with decreasing reactant (oxygen) concentration remain elusive, making it important to critically evaluate the experimental methods used to measure ROS production. In the present paper superoxide production in isolated perfused rat hearts was monitored by lucigenin chemiluminescence or dihydroethidine (DHE) oxidation product fluorescence in parallel with redox state of flavin and cytochrome oxidase. Lucigenin luminescence decreased in ischemia and increased again upon reperfusion, transiently reaching values eightfold the control value coincidently with an overshoot of mitochondrial oxygen concentration. Hypoxic perfusion decreased lucigenin chemiluminescence in spite of coronary flow increase, whereas change in lucigenin concentration in the perfusate had negligible effect. In contrast to lucigenin luminescence, the fluorescence of the DHE oxidation product increased continuously during a 30-min global ischemia and decreased precipitously upon reperfusion, this change is coincident with absorption changes of the oxygen-binding protein myoglobin. The time course of DHE oxidation product fluorescence during ischemia and reperfusion was similar to that of the mitochondrial membrane potential probe safranin as shown in perfused heart previously [Ylitalo KV, Ala-Rämi A, Liimatta EV, Peuhkurinen KJ, Hassinen IE. J Mol Cell Cardiol 2000;32:1223–38]. In solution under high oxygen partial pressure DHE was mainly oxidized to a product, whose fluorescence, absorbance and mass spectra were similar to ethidium, and this product behaved like a mitochondrial membrane potential probe in isolated mitochondria. As a membrane permeable cation it accumulates into the mitochondria when the membrane potential is high (high intramitochondrial concentration quenches fluorescence) and then is released (increased fluorescence) during hypoxia/ischemia. Upon reperfusion it is re-accumulated in the mitochondria as the membrane potential recovers. The non-specific oxidation of DHE makes this dye less suitable for superoxide detection in experiments on isolated perfused hearts that necessitate high oxygen partial pressure in the perfusate. The time course of lucigenin luminescence during ischemia/reperfusion is consistent with decreased ROS production during ischemia/hypoxia, while the oxygen concentration is decreased, followed by an overshoot when the heart tissue is reperfused and the oxygen pressures return to normal or above normal.

Microvascular Tissue Oxygenation and Oxidative Metabolism Changes in the Pedicled Latissimus Dorsi Muscle During Graded Hypoxia: Correlation Between Near Infrared and 31P Nuclear Magnetic Resonance Spectroscopy

In this study, the microvascular tissue oxygenation and oxidative muscle metabolism during graded hypoxia and reoxygenation were examined in a rabbit model by near-infrared (NIR) spectroscopy and correlated with high-energy phosphates measured by (31)P nuclear magnetic resonance (NMR) spectroscopy. Graded hypoxia was performed in a New Zealand rabbit model (n = 20, 2.0 ± 0.4 kg) by a stepwise reduction of the fraction of inspired oxygen (FiO(2)) from 0.3 to 0.05 (intervention group versus control group). Recovery and reoxygenation were achieved using FiO(2) of 0.3. A noninvasive NIR spectroscopy sensor and NMR probe was positioned on the surface of the prepared pedicled latissimus dorsi muscle. Microvascular tissue oxygenation (oxyhemoglobin, HbO(2); deoxyhemoglobin, HHb) and redox state of cytochrome oxidase (CytOx) were measured by NIR spectroscopy and correlated with standard values of oxidative muscle metabolism (phosphocreatine, PCr; adenosine triphosphate, ATP) measured by time-resolved (31)P NMR spectroscopy (4.7T). Significant correlation was found between PCr and HbO(2) (r = 0.85, P < 0.001) and HHb (r = -0.75, P < 0.001). β-ATP levels correlated significantly with CytOx (r = 0.87, P < 0.001). The data suggest that changes in high-energy phosphates (PCr- and ATP-levels) correlate closely with microvascular tissue oxygenation (HbO(2), HHb, CytOx) measured by NIR spectroscopy.

Glycine maintains mitochondrial activity and bile composition following warm liver ischemia‐reperfusion injury

Experimental studies have shown protective effect by the non-essential amino acid glycine to liver ischemia-reperfusion (I/R) injury but the mechanism of action is unknown. A rabbit model of hepatic lobar I/R was used. Three groups of animals (n=6) were studied: Sham group (laparotomy alone), ischemia reperfusion (I/R) group (1 h of liver lobar ischemia and 6 h of reperfusion), and a glycine I/R group (intravenous glycine 5 mg/kg prior to the I/R protocol). Systemic and hepatic hemodynamics, degree of liver injury (bile flow, transaminases), hepatic microcirculation, mitochondrial activity (redox state of cytochrome oxidase), bile composition and cytokines (tumor necrosis factor-α and interleukin-8) were measured during the experiment. Glycine administration increased portal blood flow, bile production, hepatic microcirculation and maintained cytochrome oxidase activity as compared with the I/R group during reperfusion. Glycine also reduced bile lactate surge and stimulated acetoacetate release in bile during reperfusion versus the I/R group. Cytokine levels (tumor necrosis factor-α, interleukin-8) and hepatocellular injury (aspartate aminotransferase and alanine aminotransferase) were significantly reduced by glycine administration. Intravenous glycine administration reduces liver warm I/R injury by reducing the systemic inflammatory response, and maintaining cellular energy production.

Importance of real-time tissue oximetry: relationship to muscle oxygenation and tissue viability

Background: There is currently no efficient and reliable clinical means of assessing the degree of ischemia and reperfusion associated damage in tissue during extracorporeal perfusion. The objective was to study correlation of tissue oxygen tension measurements with tissue oxygen saturation, cytochrome oxidase redox state and tissue viability.

Importance of Real-Time Tissue Oximetry: Relationship to Muscle Oxygenation and Tissue Viability

There is currently no efficient and reliable clinical means of assessing the degree of ischemia- and reperfusion-associated damage in microvascular transplants. The objective was to study correlation of tissue oxygen tension measurements with tissue oxygen saturation, cytochrome oxidase redox state, and tissue viability. Latissimus dorsi muscle was dissected and mobilized in New Zealand white rabbits (n = 30, 2.5 ± 0.5 kg). Muscles were exposed to warm ischemia in two groups with either 4 or 6 h, followed by reperfusion. Tissue PO(2) was measured with a miniature intramuscular oxygen sensor (Licox microprobe; Integra Neurosciences, Ratingen, Germany) all along with tissue hemoglobin saturation (rSO(2)) and cytochrome oxidase aa3 redox state (CytOx) by in vivo near-infrared spectroscopy. Linear correlation was performed between tissue PO(2) and rSO(2), CytOx and tissue viability. After ischemia and reperfusion, tissue PO(2) and CytOx recovery was significantly decreased in both groups compared with control (4 h: P < 0.05; 6 h: P < 0.01). Significant correlations between changes in tissue PO(2) and rSO(2) (r = 0.92; P < 0.01), CytOx (r = 0.90; P < 0.01), wet-to-dry ratio (r = -0.97; P < 0.01), and mitochondrial viability index (r = 0.97; P < 0.01) were found. Tissue oxygen tension measured with microprobes correlated closely with tissue oxygenation, cellular oxygen utilization, and the extent of ischemia reperfusion injury.

Brain oxymetry in the operating room: current status and future directions with particular regard to cytochrome oxidase

Near-infrared spectroscopy (NIRS) is a cerebral monitoring method that noninvasively and continuously measures cerebral hemoglobin oxygenation and the redox state of cytochrome oxidase using highly tissue-permeable near-infrared light. This technique now has wide clinical application, and its usefulness in the measurement of cerebral hemoglobin oxygenation has been confirmed under global cerebral injury and/or hypoxemic hypoxia; however, regional cerebral infarction located far from the monitoring site may not be detected by NIRS. Furthermore, the specificity and accuracy of the measurement of the redox state of cytochrome oxidase remain controversial. We apply NIRS to both animal and clinical investigations. Based on these results, we discuss the significance of the measurement of cerebral hemoglobin oxygenation and cytochrome oxidase in vivo and in clinical medicine. Using our algorithm, cytochrome oxidase signals are unaffected by hemoglobin signals, even when hematocrit values change from 35 to 5% under cardiopulmonary bypass in a dog model. In the clinical study, cytochrome oxidase during surgery is likely to be a good (though not perfect) predictor of postoperative cerebral outcome. NIRS appears to be a promising technology, but additional investigations are required to establish its clinical efficacy and justify its routine use during operative and perioperative periods.

Nitric oxide increases oxidative phosphorylation efficiency

We have studied the effect of nitric oxide (NO) and potassium cyanide (KCN) on oxidative phosphorylation efficiency. Concentrations of NO or KCN that decrease resting oxygen consumption by 10-20% increased oxidative phosphorylation efficiency in mitochondria oxidizing succinate or palmitoyl-L-carnitine, but not in mitochondria oxidizing malate plus glutamate. When compared to malate plus glutamate, succinate or palmitoyl-L-carnitine reduced the redox state of cytochrome oxidase. The relationship between membrane potential and oxygen consumption rates was measured at different degrees of ATP synthesis. The use of malate plus glutamate instead of succinate (that changes the H(+)/2e(-) stoichiometry of the respiratory chain) affected the relationship, whereas a change in membrane permeability did not affect it. NO or KCN also affected the relationship, suggesting that they change the H(+)/2e(-) stoichiometry of the respiratory chain. We propose that NO may be a natural short-term regulator of mitochondrial physiology that increases oxidative phosphorylation efficiency in a redox-sensitive manner by decreasing the slipping in the proton pumps.

Ischemic Vasoconstriction And Tissue Energy Metabolism during Global Cerebral Ischemia in Gerbils

Vasoconstriction is known to occur in cerebral arterioles during ischemia and considered to be distinct from vasospasm seen after subarachnoid hemorrhage. To elucidate the mechanism and functional significance underlying ischemic vasoconstriction, we investigated the relationship between arteriolar constriction and tissue energy metabolism during bilateral common carotid artery occlusion in gerbils. Using video microscopy and microspectroscopy, the arteriolar caliber, the total hemoglobin (Hb) content, and the redox state of cytochrome oxidase (cyt.aa3) were monitored in the cerebral cortex in vivo. After in situ freezing of the brain, adenine nucleotides, creatine phosphate (P-Cr), and lactate levels were analyzed using high-performance liquid chromatography in vitro. Tissue damage was also assessed immunohistochemically using antibodies against microtubule-associated proteins. There was a slight reduction of the diameter of pial arterioles during the initial 1 min of ischemia. A rapid decline of total Hb and reduction of cyt.aa3 were observed with rapid decreases of P-Cr and ATP in the cortical tissue during the initial 0.5 min, but all of them showed tendencies to return toward preischemic levels at 0.5-1 min. Beyond 1.5 min, extensive vasoconstriction occurred together with further decline of total Hb, reduction of cyt.aa3, and decreases of ATP and P-Cr. Neuronal damage developed in the cerebral cortex immunohistochemically beyond 3 min. The present investigation demonstrated two phases of vasoconstriction with the possibilities that the immediate vasoconstriction likely contributed to transient improvement of cortical oxygen/energy metabolism, and the second extensive vasoconstriction was an index of tissue energy failure and imminent neuronal damage.

Formation and role of plasma S-nitrosothiols in liver ischemia-reperfusion injury

Plasma S-nitrosothiols (RSNOs) may act as a circulating form of nitric oxide that affects vascular function and platelet aggregation. Their role in liver ischemia/reperfusion (I/R) injury is largely unknown. The aim of the present study was to investigate the changes in plasma RSNOs following liver I/R injury. Two groups of New Zealand white rabbits were used ( n=6, each): the I/R group underwent 60 min lobar liver ischemia and 7 h reperfusion, while the sham group underwent laparotomy but no liver ischemia. Serial RSNO levels were measured in plasma by electron paramagnetic resonance (EPR) spectrometry, nitrite/nitrates by capillary electrophoresis, hepatic microcirculation by laser Doppler flowmetry, redox state of hepatic cytochrome oxidase by near-infrared spectroscopy, liver iNOS mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) and the oxidation of dihydrorhodamine to rhodamine by fluorescence. The effect of the antioxidant N-acetylcysteine (NAC) on RSNOs formation and DHR oxidation was tested in a third group of animals ( n=6) undergoing lobar liver I/R. Hepatic I/R was associated with a significant increase in plasma RSNOs, plasma nitrites, hepatic iNOS mRNA expression, impairment in hepatic microcirculation, decrease in the redox state of cytochrome oxidase, and significant production of rhodamine. The changes were more obvious during the late phase of reperfusion (>4 h). NAC administration decreased plasma RSNOs and oxidation of DHR to RH ( P<0.05, 5 and 7 h postreperfusion, respectively). These results suggest that significant upregulation of nitric oxide synthesis during the late phase of reperfusion is associated with impairment in microcirculation and mitochondrial dysfunction. Plasma S-nitrosothiols are a good marker of this nitric oxide-mediated hepatotoxicity.

Regulation of cytochrome oxidase redox state during umbilical cord occlusion in preterm fetal sheep

The preterm fetus is capable of surviving prolonged periods of severe hypoxia without neural injury for much longer than at term. To evaluate the hypothesis that regulated suppression of brain metabolism contributes to this remarkable tolerance, we assessed changes in the redox state of cytochrome oxidase (CytOx) relative to cerebral heat production, and cytotoxic edema measured using cerebral impedance, during 25 min of complete umbilical cord occlusion or sham occlusion in fetal sheep at 0.7 gestation. Occlusion was followed by rapid, profound reduction in relative cerebral oxygenation and EEG intensity and an immediate increase in oxidized CytOx, indicating a reduction in electron flow down the mitochondrial electron transfer chain. Confirming rapid suppression of cerebral metabolism there was a loss of the temperature difference between parietal cortex and body at a time when carotid blood flow was maintained at control values. As occlusion continued, severe hypotension/hypoperfusion developed, with a further increase in CytOx levels to a plateau between 8 and 13 min and a progressive rise in cerebral impedance. In conclusion, these data strongly suggest active regulation of cerebral metabolism during the initial response to severe hypoxia, which may help to protect the immature brain from injury.

Near-Infrared Spectroscopic Analysis of Hemodynamics and Mitochondrial Redox in Right Lobe Grafts in Living-Donor Liver Transplantation

Near-infrared spectroscopy (NIRS), which enables non-destructive evaluation of hemoglobin (Hb) oxygenation and the redox state of cytochromeoxidase (Cyt.aa3) in living tissues, has been employed during surgery to detect possible impairment of hemodynamics and mitochondrial respiration in the anterior segment of a right lobe liver graft in living-donor liver transplantation (LDLT). Thirty-six patients undergoing LDLT using a right lobe graft without the middle hepatic vein (MHV) were enrolled in this study. During the course of harvesting and implantation, NIRS measurements were performed on the anterior segments of the liver grafts. In two recipients of liver grafts with Hb residue over 70% in the anterior segment after ex vivo flushing, the MHV tributary was reconstructed, while it was not reconstructed in the other 34 recipients. Of those 34 recipients, 16 recipients of liver graft with 40-70% Hb residue showed transient increase of transaminase levels after LDLT. Of those 16 recipients, six recipients who showed reduction in oxidized Cyt.aa3 in the anterior segment suffered from persistent hyperbilirubinemia after LDLT. In patients showing impairment of mitochondrial redox associated with congestion caused by deprivation of the MHV tributaries, reconstruction of the MHV tributaries might have a beneficial effect.

Investigation of the cerebral haemoglobin and cytochrome signals using near infrared spectroscopy during head up tilt in patients with orthostatic hypotension

Introduction: The cardiovascular and cerebrovascular responses to head up postural change are severely compromised in primary autonomic failure (AF) because of sympathetic denervation. AF patients therefore exhibit hypotension and show signs of cerebral hypoperfusion during a head-up tilt. In this study we employed near infrared spectroscopy (NIRS) to investigate changes in haemoglobin and cytochrome oxidase redox state ([CytOx]) during periods of severe cerebral hypoperfusion defined as a drop in cerebral haemoglobin difference ([Hbdiff]=[oxyhaemoglobin]-[deoxyhaemoglobin]) of at least 10µmol/l [1]. Methods: 12 patients were studied and data were recorded (i) when supine and (ii) during passive head up tilt to 60° degrees. A continuous wave four wavelength NIRS system (NIRO 300, Hamamatsu Photonics KK) measured changes in cerebral tissue oxyhaemoglobin ([HbO2]) and deoxyhaemoglobin ([HHb]) and [HbT]=[HbO2]+[HHb] and [CytOx] using an age corrected differential pathlength factor [2]. Beat-to-beat blood pressure (BP) was measured non-invasively using a Portapres® system. Using the [Hbdiff] signal we identified the start of the head up tilt and the maximum drop and acquired 5 sequences of 10sec mean values from the start to the maximum of the drop. Results: 8 patients demonstrated a maximum drop in the [Hbdiff] signal of at least 10µmol/l, 6 patients (group a) demonstrated a reduction in [CytOx] and 2 patients (group b) exhibited no change, which was unrelated to the drop in the other signals. These mean changes (±SD) are shown in the figure. Conclusions: We have shown that in some AF patients postural hypotension is associated with a reduction in [Hbdiff] accompanied by a fall in [CytOx], possibly indicating severe cerebral cellular dysoxia. The pattern of [CytOx] change shown in Group a, has previously been demonstrated using NIRS [3]. In 2 patients there is no response in the [CytOx] signal. It has been reported that large changes in chromophore concentrations, can lead to artifacts in the observed changes in low concentration chromophores, such as [CytOx] [4], in the data presented here there is no evidence of crosstalk between the haemoglobin and [CytOx] signals. However individual differences in the anatomy of the different layers of the adult head (scalp/skull and brain) could introduce ‘contamination’ to the [CytOx] signal [5]. Measurement of [CytOx] might be a useful adjunct during monitoring of cerebral ischaemia. References

Principles, techniques, and limitations of near infrared spectroscopy.

In the last decade the study of the human brain and muscle energetics underwent a radical change, thanks to the progressive introduction of noninvasive techniques, including near-infrared (NIR) spectroscopy (NIRS). This review summarizes the most recent literature about the principles, techniques, advantages, limitations, and applications of NIRS in exercise physiology and neuroscience. The main NIRS instrumentations and measurable parameters will be reported. NIR light (700-1000 m) penetrates superficial layers (skin, subcutaneous fat, skull, etc.) and is either absorbed by chromophores (oxy- and deoxyhemoglobin and myoglobin) or scattered within the tissue. NIRS is a noninvasive and relatively low-cost optical technique that is becoming a widely used instrument for measuring tissue O2 saturation, changes in hemoglobin volume and, indirectly, brain/muscle blood flow and muscle O2 consumption. Tissue O2 saturation represents a dynamic balance between O2 supply and O2 consumption in the small vessels such as the capillary, arteriolar, and venular bed. The possibility of measuring the cortical activation in response to different stimuli, and the changes in the cortical cytochrome oxidase redox state upon O2 delivery changes, will also be mentioned.

Intraoperative near-infrared spectroscopy for evaluating hepatic venous outflow in living-donor right lobe liver.

This study was performed to determine the usefulness of intraoperative near-infrared spectroscopy (NIRS) for evaluating the extent of congestion in the anterior segment of the graft after living-donor liver transplantation using right lobe grafts that do not have the middle hepatic vein. Fifteen patients undergoing living-donor liver transplantation using a right lobe graft without the middle hepatic vein were enrolled in this study. During the course of harvesting and implantation, in vivo NIRS was performed on the liver grafts to determine hemoglobin (Hb) and cytochrome oxidase content in the hepatic tissues. The 15 cases were divided into three groups according to the caliber of the middle hepatic vein tributaries in the right lobe grafts: the small group (<4 mm), the intermediate group (4-7 mm), and the large group (>7 mm). After implantation, congestion (increase in tissue Hb) in the anterior segment was more severe than that in the posterior segment in the intermediate and large groups. However, well-preserved mitochondrial cytochrome oxidase redox state was observed in both segments except for two cases in the large group with severe congestion in the anterior segment. The extent of postoperative congestion in the anterior segment was significantly correlated with the tissue content of remaining Hb in that segment after ex vivo flushing. Intraoperative NIRS enables quantification of the extent of congestion in the anterior segment after implantation of a right lobe liver graft and even enables prediction of such congestion at the phase of ex vivo perfusion.

Measurement of changes in cytochrome oxidase redox state during obstructive sleep apnea using near-infrared spectroscopy.

To use near-infrared spectroscopy to investigate the effect of obstructive sleep apnea on cytochrome oxidase, the terminal enzyme of the mitochondrial respiratory chain. Observational study. Teaching hospital sleep unit. Subjects with diagnosed moderate to severe obstructive sleep apnea were recruited from the sleep clinic. Subjects were invited to attend 2 daytime sleep-study sessions, which included near-infrared monitoring of cerebral oxygenation and cytochrome-oxidase oxidation state. In addition, in study session 1, full polysomnography was performed (8 subjects, 303 apneas), and in study session 2, arterial oxygen saturation, cerebral blood flow velocity, and blood pressure were monitored (7 subjects, 287 apneas). In study session 1, mean (+/- SD) cytochrome-oxidase changes ranged from 0.48 +/- 0.08 microM to 0.13 +/- 0.05 microM. The magnitude of cytochrome-oxidase change correlated significantly with the magnitude of change in the cerebral tissue oxygenation index (P < .001). In study session 2, there were significant correlations between arterial oxygen-saturation changes and cytochrome-oxidase redox changes and between Doppler cerebral blood flow velocity changes and cytochrome-oxidase redox changes (P < .001 and P = .001, respectively). Changes in directly measured cerebral tissue saturation and changes in arterial saturation and cerebral blood flow velocity (the 2 main factors affecting cerebral oxygenation) are associated with changes in cytochrome-oxidase oxidation state. The reduced cerebral oxygenation that occurs during obstructive sleep apnea is associated with changes in the intracellular redox state.