Harms Floor Anneleen, Stolker Robert Jan, Mik Egbert Gezinus
Department of Anesthesiology, Laboratory of Experimental Anesthesiology, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Department of Intensive Care, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
PLoS One. 2016 Jul 25;11(7):e0159544. doi: 10.1371/journal.pone.0159544. eCollection 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 recorded before and during a 60-s period of compression of the microcirculation, at an interval of 1 Hz. Oxygen consumption (i.e. the local oxygen disappearance rate) was calculated from the decay of the mitoPO2 slope.
Oxygen-dependent delayed fluorescence measurements were successfully performed in the skin of 27 volunteers. The average value (± SD) of mitoPO2 was 44 ± 17 mmHg and mean mitoVO2 values were 5.8 ± 2.3 and 6.1 ± 1.6 mmHg s-1 at a skin temperature of 34°C and 40°C, respectively. No major discomfort during measurement and no long-term dermatological abnormalities were reported in a survey performed 1 month after measurements.
These results show that the clinical prototype allows measurement of mitochondrial oxygenation and oxygen consumption in humans. The development of this clinically applicable device offers opportunities for further evaluation of the technique in humans and the start of first clinical studies.
原卟啉IX三线态寿命技术（PpIX - TSLT）被提议作为一种监测线粒体功能的潜在临床无创工具。该技术已在多项动物研究中得到评估。线粒体呼吸测定法可在体内测量皮肤中线粒体氧张力（mitoPO2）和线粒体氧消耗（mitoVO2）。本研究描述了该临床原型在人体皮肤中的首次应用。
在30名健康志愿者身上测试了该临床原型。将含有2毫克5 - 氨基酮戊酸（ALA）的自粘贴片贴在前胸壁（胸骨处）皮肤上，以诱导线粒体原卟啉IX，并避光5小时。通过原卟啉IX的氧依赖延迟荧光测量mitoPO2。通过对预处理皮肤进行动态mitoPO2测量来测定mitoVO2，同时用测量探头施加局部压力以局部阻断氧气供应。在微循环压缩60秒之前和期间，以1赫兹的间隔记录mitoPO2。根据mitoPO2斜率的衰减计算氧消耗（即局部氧消失率）。
在27名志愿者的皮肤中成功进行了氧依赖延迟荧光测量。在皮肤温度分别为34°C和40°C时，mitoPO2的平均值（±标准差）为44±17 mmHg，mitoVO2的平均值分别为5.8±2.3和6.1±1.6 mmHg s-1。测量期间未报告有重大不适情况，在测量后1个月进行的一项调查中也未报告有长期皮肤异常情况。
这些结果表明，该临床原型能够测量人体线粒体氧合和氧消耗。这种临床适用设备的开发为在人体中进一步评估该技术以及开展首批临床研究提供了机会。
