Cutaneous Respirometry as Novel Technique to Monitor Mitochondrial Function: A Feasibility Study in Healthy Volunteers

Harms, Floor A.; Stolker, Robert Jan; Mik, Egbert G.

doi:10.1371/journal.pone.0159544

Cited by 24 publications

(42 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The “canary” function of human skin in relation to organ function still needs further investigation but important is that also changes in cutaneous mitochondrial oxygen consumption correlate with ODR changes in other organs and tissues [ 17 ]. The ODR from the dynamic measurement 6.3 mmHg s −1 in this example corresponds with previous data from healthy volunteers 5.8 ± 2.3 mmHg s −1 [ 29 ] .…”

Section: Discussionsupporting

confidence: 86%

See 1 more Smart Citation

A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level

Ubbink

Bettink

Janse

et al. 2016

J Clin Monit Comput

View full text Add to dashboard Cite

After introduction of the protoporphyrin IX-triplet state lifetime technique as a new method to measure mitochondrial oxygen tension in vivo, the development of a clinical monitor was started. This monitor is the “COMET”, an acronym for Cellular Oxygen METabolism. The COMET is a non-invasive electrically powered optical device that allows measurements on the skin. The COMET is easy to transport, due to its lightweight and compact size. After 5-aminolevulinic acid application on the human skin, a biocompatible sensor enables detection of PpIX in the mitochondria. PpIX acts as a mitochondrially located oxygen-sensitive dye. Three measurement types are available in the touchscreen-integrated user interface, ‘Single’, ‘Interval’ and ‘Dynamic measurement’. COMET is currently used in several clinical studies in our institution. In this first description of the COMET device we show an incidental finding during neurosurgery. To treat persisting intraoperative hypertension a patient was administered clonidine, but due to rapid administration an initial phase of peripheral vasoconstriction occurred. Microvascular flow and velocity parameters measured with laser-doppler (O2C, LEA Medizintechnik) decreased by 44 and 16% respectively, but not the venous-capillary oxygen saturation. However, mitochondrial oxygen tension in the skin detected by COMET decreased from a steady state of 48 to 16 mmHg along with the decrease in flow and velocity. We conclude that COMET is ready for clinical application and we see the future for this bedside monitor on the intensive care, operating theater, and testing of mitochondrial effect of pharmaceuticals.

show abstract

Section: Discussionsupporting

confidence: 86%

“…Till now the feasibility of measuring mitoPO 2 and mitoVO 2 with PpIX-TSLT was tested in healthy volunteers [ 29 ] and is currently further evaluated with COMET in the perioperative setting. However, the original main development idea of COMET was the in vivo determination of aspects of mitochondrial (dys)function in critical illness.…”

Section: Discussionmentioning

confidence: 99%

A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level

Ubbink

Bettink

Janse

et al. 2016

J Clin Monit Comput

View full text Add to dashboard Cite

show abstract

“…However, it needs to be confirmed that MID patients with involvement of the skin indeed show abnormal mito-pO 2 or mito-VO 2 on cutaneous respirometry. In a study of 30 healthy controls, reference limits of mito-pO 2 are given as 44 ± 17 mm Hg, and those of mito-VO 2 as 5.8 ± 2.3 mm Hg at 34 degrees Celsius [ 24 ]. The study showed that cutaneous respirometry allows measurement of mitochondrial oxygenation and oxygen consumption in humans [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

Biomarkers for Detecting Mitochondrial Disorders

Finsterer

Zarrouk‐Mahjoub

2018

JCM

View full text Add to dashboard Cite

(1) Objectives: Mitochondrial disorders (MIDs) are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2) Methods: Literature review. (3) Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), MR-spectroscopy (MRS), positron emission tomography (PET), or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF) for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4) Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available) and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

show abstract

“…Spectroscopic approaches, including broadband spectroscopy, allowed for measurement of the oxidative state of cellular cytochromes which reflect cellular energetics [ 32 , 33 ]. Measurement of cutaneous mitochondrial PO 2 , utilizing the oxygen-dependent delayed fluorescence of protopor-phyrin IX in the skin [ 34 , 35 ], has been used to assess the mitochondrial PO 2 response to acute hemodilution in an experimental pig model [ 35 ]. This approach was able to detect tissue hypoxia at an earlier stage of hemodilution relative to more traditional measurements including changes in MAP, serum lactate, VO 2 , and NIRS [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Experimental assessment of oxygen homeostasis during acute hemodilution: the integrated role of hemoglobin concentration and blood pressure

Kei

Mistry

Tsui

et al. 2017

ICMx

View full text Add to dashboard Cite

BackgroundLow hemoglobin concentration (Hb) and low mean arterial blood pressure (MAP) impact outcomes in critically ill patients. We utilized an experimental model of “normotensive” vs. “hypotensive” acute hemodilutional anemia to test whether optimal tissue perfusion is dependent on both Hb and MAP during acute blood loss and fluid resuscitation, and to assess the value of direct measurements of the partial pressure of oxygen in tissue (PtO2).MethodsTwenty-nine anesthetized rats underwent 40% isovolemic hemodilution (1:1) (or sham-hemodilution control, n = 4) with either hydroxyethyl starch (HES) (n = 14, normotensive anemia) or saline (n = 11, hypotensive anemia) to reach a target Hb value near 70 g/L. The partial pressure of oxygen in the brain and skeletal muscle tissue (PtO2) were measured by phosphorescence quenching of oxygen using G4 Oxyphor. Mean arterial pressure (MAP), heart rate, temperature, arterial and venous co-oximetry, blood gases, and lactate were assessed at baseline and for 60 min after hemodilution. Cardiac output (CO) was measured at baseline and immediately after hemodilution. Data were analyzed by repeated measures two-way ANOVA.ResultsFollowing “normotensive” hemodilution with HES, Hb was reduced to 66 ± 6 g/L, CO increased (p < 0.05), and MAP was maintained. These conditions resulted in a reduction in brain PtO2 (22.1 ± 5.6 mmHg to 17.5 ± 4.4 mmHg, p < 0.05), unchanged muscle PO2, and an increase in venous oxygen extraction. Following “hypotensive” hemodilution with saline, Hb was reduced to 79 ± 5 g/L and both CO and MAP were decreased (P < 0.05). These conditions resulted in a more severe reduction in brain PtO2 (23.2 ± 8.2 to 10.7 ± 3.6 mmHg (p < 0.05), a reduction in muscle PtO2 (44.5 ± 11.0 to 19.9 ± 12.4 mmHg, p < 0.05), a further increase in venous oxygen extraction, and a threefold increase in systemic lactate levels (p < 0.05).ConclusionsAcute normotensive anemia (HES hemodilution) was associated with a subtle decrease in brain tissue PtO2 without clear evidence of global tissue hypoperfusion. By contrast, acute hypotensive anemia (saline hemodilution) resulted in a profound decrease in both brain and muscle tissue PtO2 and evidence of inadequate global perfusion (lactic acidosis). These data emphasize the importance of maintaining CO and MAP to ensure adequacy of vital organ oxygen delivery during acute anemia. Improved methods of assessing PtO2 may provide an earlier warning signal of vital organ hypoperfusion.

show abstract

Cutaneous Respirometry as Novel Technique to Monitor Mitochondrial Function: A Feasibility Study in Healthy Volunteers

Cited by 24 publications

References 34 publications

A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level

A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level

Biomarkers for Detecting Mitochondrial Disorders

Experimental assessment of oxygen homeostasis during acute hemodilution: the integrated role of hemoglobin concentration and blood pressure

Contact Info

Product

Resources

About