Mitochondrial oxygen tension within the heart

Mik, Egbert G.; İnce, Can; Eerbeek, Otto; Heinen, André; Stap, Jan; Hooibrink, Berend; Schumacher, Cees A.; Balestra, G; Johannes, Tanja; Beek, Hans van; Nieuwenhuis, Albert F.; Horssen, Pepijn van; Spaan, Jos A. E.; Zuurbier, Coert J.

doi:10.1016/j.yjmcc.2009.02.002

Cited by 65 publications

(62 citation statements)

References 51 publications

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“…In its calibrated form, the technique of oxygendependent quenching of delayed fluorescence of PpIX allows for the measurement of mitochondrial oxygen tension in living cells [10] and ex vivo and in vivo tissues [12,13]. For its application in skin, the calibration constants remain to be determined, but the oxygen-dependence of the signal was evident in the present study from analysis of the reciprocal lifetime distributions.…”

Section: Discussionmentioning

confidence: 84%

“…5-Aminolevulinic acid (ALA) enhanced PpIX is synthesized inside the mitochondria [11] and can act as mitochondrially located oxygen-sensitive dye. We successfully measured mitochondrial PO 2 (mitoPO 2 ) in cultured cells [10], rat liver [12] and rat heart [13].…”

Section: Biophotonicsmentioning

confidence: 99%

“…Although the calibration constants have been determined in rat liver [12] and rat heart [13], t 0 and k q are not validated for our current application in skin. Especially the temperature dependency of t 0 and k q remain to be determined.…”

Section: Lifetime Analysismentioning

confidence: 99%

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Oxygen‐dependent delayed fluorescence measured in skin after topical application of 5‐aminolevulinic acid

Harms

Boon

Balestra

et al. 2011

Journal of Biophotonics

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Mitochondrial oxygen tension can be measured in vivo by means of oxygen‐dependent quenching of delayed fluorescence of protoporphyrin IX (PpIX). Here we demonstrate that delayed fluorescence is readily observed from skin in rat and man after topical application of the PpIX precursor 5‐aminolevulinic acid (ALA). Delayed fluorescence lifetimes respond to changes in inspired oxygen fraction and blood supply. The signals contain lifetime distributions and the fitting of rectangular distributions to the data appears more adequate than mono‐exponential fitting. The use of topically applied ALA for delayed fluorescence lifetime measurements might pave the way for clinical use of this technique. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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Section: Discussionmentioning

confidence: 84%

Section: Biophotonicsmentioning

confidence: 99%

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Oxygen‐dependent delayed fluorescence measured in skin after topical application of 5‐aminolevulinic acid

Harms

Boon

Balestra

et al. 2011

Journal of Biophotonics

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“…However, this does not necessarily mean that because workload is lower in isolated hearts, they are less prone to hypoxia; oxygen delivery in the isolated buffer-perfused heart is significantly worse than is achieved in vivo. Recent work by Mik et al [41] has shown that mitochondrial pO 2 levels are generally lower in isolated hearts than when in vivo, and the model can only be considered representative of the in vivo situation when they are maximally vasodilated. As such, while monitoring oxygen concentrations in cells or tissues may be a useful means of comparing the hypoxia selectivity of one tracer with another in any given model, using tissue oxygen levels as the key to translate tracer behavior across models or to the in vivo situation must be done with caution.…”

Section: Requirements Of An Ideal Cardiac Hypoxia Imaging Agentmentioning

confidence: 99%

PET imaging of cardiac hypoxia: Opportunities and challenges

Handley¹,

Medina²,

Nagel

et al. 2011

Journal of Molecular and Cellular Cardiology

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Myocardial hypoxia is a major factor in the pathology of cardiac ischemia and myocardial infarction. Hypoxia also occurs in microvascular disease and cardiac hypertrophy, and is thought to be a prime determinant of the progression to heart failure, as well as the driving force for compensatory angiogenesis. The non-invasive delineation and quantification of hypoxia in cardiac tissue therefore has the potential to be an invaluable experimental, diagnostic and prognostic biomarker for applications in cardiology. However, at this time there are no validated methodologies sufficiently sensitive or reliable for clinical use. PET imaging provides real-time spatial information on the biodistribution of injected radiolabeled tracer molecules. Its inherent high sensitivity allows quantitative imaging of these tracers, even when injected at subpharmacological (≥pM) concentrations, allowing the non-invasive investigation of biological systems without perturbing them. PET is therefore an attractive approach for the delineation and quantification of cardiac hypoxia and ischemia. In this review we discuss the key concepts which must be considered when imaging hypoxia in the heart. We summarize the PET tracers which are currently available, and we look forward to the next generation of hypoxia-specific PET imaging agents currently being developed. We describe their potential advantages and shortcomings compared to existing imaging approaches, and what is needed in terms of validation and characterization before these agents can be exploited clinically.

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“…The third type of alternative probe has been employed recently in vivo (18) to measure the mitochondrial oxygen tension of the heart, bringing this noninvasive technique closer to clinical application.…”

Section: Introductionmentioning

confidence: 99%

Triplet Imaging of Oxygen Consumption During the Contraction of a Single Smooth Muscle Cell (A7r5)

Geissbuehler

Spielmann

Formey

et al. 2011

Oxygen Transport to Tissue XXXIII

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The measurement of tissue and cell oxygenation is important for understanding cell metabolism. We have addressed this problem with a novel optical technique, called triplet imaging, that exploits oxygen-induced triplet lifetime changes and is compatible with a variety of fluorophores. A modulated excitation of varying pulse widths allows the extraction of the lifetime of the essentially dark triplet state using a high-fluorescence signal intensity. This enables the monitoring of fast kinetics of oxygen concentration in living cells combined with high temporal and spatial resolution. First, the oxygen-dependent triplet-state quenching of tetramethylrhodamine is validated and then calibrated in an L-ascorbic acid titration experiment demonstrating the linear relation between triplet lifetime and oxygen concentration according to the Stern-Volmer equation. Second, the method is applied to a biological cell system, employing as reporter a cytosolic fusion protein of b-galactosidase with SNAP-tag labeled with tetramethylrhodamine. Oxygen consumption in single smooth muscle cells A7r5 during an [Arg 8 ]-vasopressin-induced contraction is measured. The results indicate a consumption leading to an intracellular oxygen concentration that decays monoexponentially with time. The proposed method has the potential to become a new tool for investigating oxygen metabolism at the single cell and the subcellular level.

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Mitochondrial oxygen tension within the heart

Cited by 65 publications

References 51 publications

Oxygen‐dependent delayed fluorescence measured in skin after topical application of 5‐aminolevulinic acid

Oxygen‐dependent delayed fluorescence measured in skin after topical application of 5‐aminolevulinic acid

PET imaging of cardiac hypoxia: Opportunities and challenges

Triplet Imaging of Oxygen Consumption During the Contraction of a Single Smooth Muscle Cell (A7r5)

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