Oxygenation measurement by multi-wavelength oxygen-dependent phosphorescence and delayed fluorescence: catchment depth and application in intact heart

Balestra, G; Aalders, Maurice C. G.; Specht, Patricia A.C.; İnce, Can; Mik, Egbert G.

doi:10.1002/jbio.201400054

Cited by 5 publications

(3 citation statements)

References 78 publications

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“…As oxygen transport from microcirculation into the tissue cells is driven by diffusion, it is generally anticipated, according to the classical oxygen cascade that mitochondrial oxygen tension should be very low (several mmHgs) to create a big enough oxygen gradient [46,47]. However, average mitoPO 2 measured with the PpIX-TSLT technique appears to be, depending on the specific tissue, close to microvascular oxygen tension [33,48] and known values for tissue and/or interstitial oxygen levels [49,50 && ]. In fact, mitoPO 2 is unlikely to be an order of magnitude lower than microvascular and interstitial oxygen tension.…”

Section: The Myth Of Low Mitopomentioning

confidence: 99%

Monitoring mitochondrial PO2: the next step

Mik

Balestra

Harms

2020

Current Opinion in Critical Care

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Purpose of reviewTo 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 findingsMitochondrial 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. SummaryPpIX-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.

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Section: The Myth Of Low Mitopomentioning

confidence: 99%

Monitoring mitochondrial PO2: the next step

Mik

Balestra

Harms

2020

Current Opinion in Critical Care

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“…We applied this technique in several studies to measure renal cortical and medulla PO 2 in different states of hemodynamic compromise (e.g., 54,59). Recently, we established the catchment depths of the multi-wavelength approach for its application to the heart (8). In this optically dense tissue, the catchment depth ranged from 160 (blue excitation) to 350 m (red excitation).…”

Section: Quenching Of Pd-porphyrin Phosphorescencementioning

confidence: 99%

Microcirculatory and mitochondrial hypoxia in sepsis, shock, and resuscitation

İnce

Mik

2016

Journal of Applied Physiology

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After shock, persistent oxygen extraction deficit despite the apparent adequate recovery of systemic hemodynamic and oxygen-derived variables has been a source of uncertainty and controversy. Dysfunction of oxygen transport pathways during intensive care underlies the sequelae that lead to organ failure, and the limitations of techniques used to measure tissue oxygenation in vivo have contributed to the lack of progress in this area. Novel techniques have provided detailed quantitative insight into the determinants of microcirculatory and mitochondrial oxygenation. These techniques, which are based on the oxygen-dependent quenching of phosphorescence or delayed luminescence are briefly reviewed. The application of these techniques to animal models of shock and resuscitation revealed the heterogeneous nature of oxygen distributions and the alterations in oxygen distribution in the microcirculation and in mitochondria. These studies identified functional shunting in the microcirculation as an underlying cause of oxygen extraction deficit observed in states of shock and resuscitation. The translation of these concepts to the bedside has been enabled by our development and clinical introduction of hand-held microscopy. This tool facilitates the direct observation of the microcirculation and its alterations at the bedside under the conditions of shock and resuscitation. Studies identified loss of coherence between the macrocirculation and the microcirculation, in which resuscitation successfully restored systemic circulation but did not alleviate microcirculatory perfusion alterations. Various mechanisms responsible for these alterations underlie the loss of hemodynamic coherence during unsuccessful resuscitation procedures. Therapeutic resolution of persistent heterogeneous microcirculatory alterations is expected to improve outcomes in critically ill patients.

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“…The mitoPO 2 measured with the COMET monitor is higher than expected. MitoPO 2 appears to be, depending on the measurement site and respiratory rate of the tissue, much closer to microvascular oxygen tension [ 19 , 20 ], and thus closer to tissue and/or interstitial oxygen levels [ 21 , 22 ], than anticipated [ 7 ]. There are several reasons why mean mitoPO 2 in a tissue sample cannot be an order of magnitude lower than microvascular and interstitial oxygen tension; first, oxygen does not disappear stepwise but gradual, so several mitochondria will see aPO 2 close to intravascular values.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial oxygen monitoring with COMET: verification of calibration in man and comparison with vascular occlusion tests in healthy volunteers

Ubbink

Bettink

Weteringen

et al. 2020

J Clin Monit Comput

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Mitochondria are the primary consumers of oxygen and therefore an important location for oxygen availability and consumption measurement. A technique has been developed for mitochondrial oxygen tension (mitoPO2) measurement, incorporated in the COMET. In contrast to most textbooks, relatively high average mitoPO2 values have been reported. The first aim of this study was to verify the validity of the COMET calibration for mitoPO2 measurements in human skin. The second aim was to compare the dynamics of mitoPO2 to several other techniques assessing tissue oxygenation. Firstly, we performed a two-point calibration. Mitochondrial oxygen depletion was achieved with vascular occlusion. A high mitoPO2 was reached by local application of cyanide. MitoPO2 was compared to the arterial oxygen partial pressure (PaO2). Secondly, for deoxygenation kinetics we compared COMET variables with the LEA O2C, SenTec OxiVenT™ and Medtronic INVOS™ parameters during a vascular occlusion test. 20 healthy volunteers were recruited and resulted in 18 datasets (2 times 9 subjects). The lowest measured mitoPO2 value per subject had a median [IQR] of 3.0 [1.0–4.0] mmHg, n = 9. After cyanide application the mitoPO2 was 94.1 mmHg [87.2–110.9] and did not differ significantly (n = 9, p = 0.5) from the PaO2 of 101.0 [98.0–106.0] mmHg. In contrast to O2C, OxiVenT™ and INVOS parameters, mitoPO2 declined within seconds with pressure on the probe. The kinetics from this decline are used to mitochondrial oxygen consumption (mitoVO2). This study validates the calibration of the COMET device in humans. For mitoVO2 measurements not only blood flow cessation but application of local pressure is of great importance to clear the measurement site of oxygen-carrying erythrocytes.

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Oxygenation measurement by multi-wavelength oxygen-dependent phosphorescence and delayed fluorescence: catchment depth and application in intact heart

Cited by 5 publications

References 78 publications

Monitoring mitochondrial PO2: the next step

Monitoring mitochondrial PO2: the next step

Microcirculatory and mitochondrial hypoxia in sepsis, shock, and resuscitation

Mitochondrial oxygen monitoring with COMET: verification of calibration in man and comparison with vascular occlusion tests in healthy volunteers

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