A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level (original) (raw)
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PLOS ONE
Introduction The newly introduced Cellular Oxygen METabolism (COMET®) monitor enables the measurement of mitochondrial oxygen tension (mitoPO2) using the protoporphyrin IX triplet state lifetime technique (PpIX-TSLT). This study aims to investigate the feasibility and applicability of the COMET® measurements in the operating theatre and study the behavior of the new parameter mitoPO2 during stable operating conditions. Methods In this observational study mitochondrial oxygenation was measured in 20 patients during neurosurgical procedures using the COMET® device. Tissue oxygenation and local blood flow were measured by the Oxygen to See (O2C). Primary outcomes included mitoPO2, skin temperature, mean arterial blood pressure, local blood flow and tissue oxygenation. Results All patients remained hemodynamically stable during surgery. Mean baseline mitoPO2 was 60 ± 19 mmHg (mean ± SD) and mean mitoPO2 remained between 40–60 mmHg during surgery, but tended to decrease over time in line...
Mitochondrial function and tissue vitality: bench-to-bedside real-time optical monitoring system
Journal of Biomedical …, 2011
Background: The involvement of mitochondria in pathological states, such as neurodegenerative diseases, sepsis, stroke, and cancer, are well documented. Monitoring of nicotinamide adenine dinucleotide (NADH) fluorescence in vivo as an intracellular oxygen indicator was established in 1950 to 1970 by Britton Chance and collaborators. We use a multiparametric monitoring system enabling assessment of tissue vitality. In order to use this technology in clinical practice, the commercial developed device, the CritiView (CRV), is tested in animal models as well as in patients. Methods and Results: The new CRV enables the optical monitoring of four different parameters, representing the energy balance of various tissues in vivo. Mitochondrial NADH is measured by surface fluorometry/reflectometry. In addition, tissue microcirculatory blood flow, tissue reflectance and oxygenation are measured as well. The device is tested both in vitro and in vivo in a small animal model and in preliminary clinical trials in patients undergoing vascular or open heart surgery. In patients, the monitoring is started immediately after the insertion of a three-way Foley catheter (urine collection) to the patient and is stopped when the patient is discharged from the operating room. The results show that monitoring the urethral wall vitality provides information in correlation to the surgical procedure performed.
Towards non‐invasive monitoring of mitochondrial function
2014
Preface and outline of this thesis Chapter 1 Oxygen-dependent delayed fluorescence measured in skin after topical application of 5-aminolevulinic acid 14 Chapter 2 Microvascular and mitochondrial PO2 simultaneously measured by oxygen-dependent delayed luminescence 34 Chapter 3 Validation of the protoporphyrin IX-triplet state lifetime technique for mitochondrial oxygen measurements in the skin 58 Chapter 4 Cutaneous respirometry by dynamic measurement of mitochondrial oxygen tension for monitoring of mitochondrial function in vivo 68 Chapter 5 A novel technique for non-invasive monitoring of mitochondrial oxygenation and respiration in critical illness 92 Chapter 6 In vivo monitoring of alterations in mitochondrial oxygen consumption. Chapter 7 Cutaneous mitochondrial respirometry: towards clinical monitoring of mitochondrial function Chapter 8 Cutaneous respirometry as novel technique to monitor mitochondrial function: a feasibility study in healthy volunteers Chapter 9 In vivo assessment of mitochondrial oxygen consumption Chapter 10 General discussion and future perspectives Chapter 11 Summary Nederlandse samenvatting Chapter 12 Dankwoord List of publications PhD portfolio Curriculum Vitae Therefore, the work in this thesis is aimed at further developing PpIX-TSLT into a clinical monitoring tool that enables early assessment of mitochondrial function in critically ill patients. PpIX-TSLT in itself allows us to measure mitochondrial oxygen tension (mitoPO 2) in an optical manner. It is the first technique that enables measurement of mitoPO 2 in living cells and tissues, and can be applied in vivo [11, 12]. The principles of the measurement are shown in Figure 1. FIGURE 1. Principle of mitoPO 2 measurement by oxygen-dependent quenching of ALA enhanced PpIX. Principle by which ALA administration enhances mitochondrial PpIX levels. ALA, 5-aminolevulinic acid; PBG, porphobilinogen; UPIII, uroporphyrinogen III; CPIII, coporporphyrinogen III; and PpIX, protoporphyrin IX. PpIX emits delayed fluorescence after excitation by a pulse of green (510 nm) light. The delayed fluorescence lifetime is oxygen-dependent according to the Stern-Volmer equation (inset), in which k q is the quenching constant and τ 0 is the lifetime at zero oxygen. Jablonski diagram of states and state transitions of PpIX and its interaction with oxygen. S 0 , S 1 , and S 2 represent the ground state and first and second excited singlet states, respectively. T 0 , T 1 , and T 2 represent the ground (triplet) state and first and second excited triplet states, respectively. k q is the rate constant of T 1 quenching by oxygen.
Current Opinion in Critical Care
Purpose of review To fully exploit the concept of hemodynamic coherence in resuscitating critically ill one should preferably take into account information about the state of parenchymal cells. Monitoring of mitochondrial oxygen tension (mitoPO 2) has emerged as a clinical means to assess information of oxygen delivery and oxygen utilization at the mitochondrial level. This review will outline the basics of the technique, summarize its development and describe the rationale of measuring oxygen at the mitochondrial level. Recent findings Mitochondrial oxygen tension can be measured by means of the protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT). After validation and use in preclinical animal models, the technique has recently become commercially available in the form of a clinical measuring system. This system has now been used in a number of healthy volunteer studies and is currently being evaluated in studies in perioperative and intensive care patients in several European university hospitals. Summary PpIX-TSLT is a noninvasive and well tolerated method to assess aspects of mitochondrial function at the bedside. It allows doctors to look beyond the macrocirculation and microcirculation and to take the oxygen balance at the cellular level into account in treatment strategies.
Advances in Biomedical Photonics and Imaging - Proceedings of the 6th International Conference on Photonics and Imaging in Biology and Medicine (PIBM 2007), 2008
The involvement of mitochondrial dysfunction in various pathophysiological conditions, developed in experimental and clinical situations, is widely documented. Nevertheless, real time monitoring of mitochondrial function in-vivo is very rare. The pressing question is how the mitochondria of intact tissues behave under in-vivo conditions as compared to isolated mitochondria that had been described by Chance and Williams over 50 years ago. This subject has been recently discussed in detail (Mayevsky and Rogatsky 2007). We reviewed the subject of evaluating mitochondrial function by monitoring NADH fluorescence together with microcirculatory blood flow, Hemoglobin oxygenation and tissue reflectance. These 4 parameters represent the vitality of the tissue and could be monitored in vivo, using optical spectroscopy, in animal models as well as in clinical practice. It is a well known physiological hypothesis that, under emergency conditions, the sympathetic nervous system will give preference to the most vital organs in the body, namely the brain, heart and adrenal glands. The less vital organs, such as the skin, GI-tract, and Urethral wall, will become hypoperfused and their mitochondrial activity will be inhibited. The monitoring of the less vital organs may reveal critical tissue conditions that may manifest an early phase of body deterioration. The aim of the current presentation is to review the experimental and preliminary clinical results accumulated using a new integrated medical device-the "CritiView" which enabled, for the first time, monitoring 4 parameters from the tissue using a single optical probe. The CritiView is a computerized optical device that integrates hardware and software in order to provide real time information on tissue vitality. In preliminary clinical testing, we used a 3-way Foley catheter that includes a bundle of optical fibers enabling the monitoring of the 4 parameters, representing the vitality of the urethral wall (a less vital organ).We found that the exposure of patients to metabolic imbalances in the operation room led to changes in tissue blood flow and inhibition of mitochondrial function in the urethral wall. In conclusion, the new device "CritiView" could provide reliable, real time data on mitochondrial function and tissue vitality in experimental animals as well as in patients.
Mitochondrial dysfunction: bench-to-bedside optical monitoring of tissue vitality
SPIE Proceedings, 2008
In normal cell the mitochondria are the major source of energy for cellular functions. They serve as biosensors for oxidative stress and involved also in termination of cell function by apoptosis. The involvement of mitochondria in pathological states such as neurodegenerative diseases, sepsis, stroke and cancer are well documented. The involvement of mitochondrial respiration and function in cancer development, proliferation and possible therapy were initiated 75 years ago by Otto Warburg. Monitoring of NADH fluorescence in vivo as an intracellular oxygen indicator was established in the 1950-1970 by Britton Chance and collaborators. In the last 20 years we developed and used a multiparametric monitoring system enabling real time assessment of mitochondria NADH, microcirculatory blood flow and volume as well as HbO 2 oxygenation. In order to use this technology in clinical practice the commercial developed device-the "CritiView" was tested in animal models as well as in patients hospitalized in the critical care departments. In patients we tested the viability of the urethral wall (a less-vital tissue) by a 3 way Foley urinary catheter that contains the optical probe. The catheter was introduced to patients underwent open heart bypass surgery or abdominal aorta aneurysm (AAA) operations. The monitoring started immediately after the insertion of the catheter to the patient and was stopped when the patient was discharged from the operation room. The results show that monitoring of the vitality of the Urethral wall provides information in correlation to the surgical procedure performed. In the AAA patients the occlusion of the aorta led to severe ischemia developed in the urethral wall and recovery of signals were recorded after the reopening of the aorta. In patients under went heart bypass surgery the urethra vitality was decreased dramatically during the operation and recovery was noted in most patients after the discharge of the patient from the operation room.
2017
In the last ten years, the use of fluorescent probes developed to measure oxygen has resulted in several marketed devices, some unreasonably expensive and with little flexibility. We have explored the use of the effective, versatile, and inexpensive Redflash technology to determine oxygen uptake by a number of different biological samples using various layouts. This technology relies on the use of an optic fiber equipped at its tip with a membrane coated with a fluorescent dye (www.pyro-science.com). This oxygen-sensitive dye uses red light excitation and lifetime detection in the near infrared. So far, the use of this technology has mostly been used to determine oxygen concentration in open spaces for environmental studies, especially in aquatic media. The oxygen uptake determined by the device can be easily assessed in small volumes of respiration medium and combined with the measurement of additional parameters, such as lactate excretion by intact cells or the membrane potential of purified mitochondria. We conclude that the performance of by this technology should make it a first choice in the context of both fundamental studies and investigations for respiratory chain deficiencies in human samples.
Monitoring of mitochondrial oxygenation during perioperative blood loss
BMJ Case Reports, 2021
One of the challenges in the management of acute blood loss is to differentiate whether blood transfusion is required or not. The sole use of haemoglobin values might lead to unnecessary transfusion in individual cases. The suggestion is that mitochondrial oxygen tension can be used as an additional monitoring technique to determine when blood transfusion is required. In this case report, we report mitochondrial oxygen measurements in a patient with perioperative blood loss requiring blood transfusion.
Acta Neurochirurgica, 2010
Object Periods of brain tissue ischemia are common after severe head injury, and their occurrence and duration are negatively correlated with outcome. Accurate and reliable measurement of brain tissue oxygenation (B ti pO 2 ) may be a key to improve patient outcome after severe head injury. Knowledge of stability and accuracy of the B ti pO 2 systems is crucial. We have therefore conducted a bench test study of new Neurovent-PTO® (NV) and Licox® (LX) oxygen tension catheters to evaluate the sensor accuracy, response time to different oxygen tensions, response to temperature changes and long-term stability. Methods For all experiments five new fluorescent NV sensors and five new electrochemical LX sensors were used. The catheter probes were placed into a container filled with a buffer solution. The solution was equilibrated with five high precision calibration gases. The accuracy of the probes was recorded after an equilibration period of 20 min in O 2 concentrations of 5, 10, 20, 30 and 40 mmHg at 37.0± 0.2°C. The probe response to an increase in temperature from 37.0°C to 38.5°C to 40.0°C in two different gases with O 2 concentrations of 10 and 20 mmHg were analysed. We also recorded the time for reaching 90% of a new oxygen concentration level when switching from one concentration to another. Finally, to test if there was a time-dependant drift in pO 2 recordings, all sensors were left in 10 mmHg O 2 solution for 10 days, and recordings were taken every 24 h. Results In all gas concentrations, NV and LX sensors measured pO 2 with high accuracy and stability in vitro (mean differences from calculated values were for NV 0.76-1.6 mmHg and for LX −0.46-0.26 mmHg). Both sensors showed a shorter response time to pO 2 increase (for NV 56±22 s and for LX 78±21 s) compared to pO 2 decrease (for NV 131±42 s and for LX 215±63 s). NV pO 2 values were more stable for changes in temperature, while LX sensors showed larger standard deviations with increasing temperature (the difference from the calculated values in 19.7 mmHg O 2 at 40°C were for NV probes between 0.5 and 1.7 mmHg and LX between −2.3 and 1.9 mmHg). Both sensors gave stable results with low standard deviations during long-term (10 days) use, but with a slight elevation of measured pO 2 levels by time.
PloS one, 2016
The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) is proposed as a potential clinical non-invasive tool to monitor mitochondrial function. This technique has been evaluated in several animal studies. Mitochondrial respirometry allows measurement in vivo of mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in skin. This study describes the first use of a clinical prototype in skin of humans. The clinical prototype was tested in 30 healthy volunteers. A self-adhesive patch containing 2 mg 5-aminolevulinic acid (ALA) was applied on the skin of the anterior chest wall (sternal) for induction of mitochondrial protoporphyrin IX and was protected from light for 5 h. MitoPO2 was measured by means of oxygen-dependent delayed fluorescence of protoporphyrin IX. MitoVO2 was determined by dynamic mitoPO2 measurements on the primed skin, while locally blocking oxygen supply by applying local pressure with the measurement probe. MitoPO2 was reco...