SHEDDING LIGHT ON LIFE: OPTICAL ASSESSMENT OF MITOCHONDRIAL FUNCTION AND TISSUE VITALITY IN BIOLOGY AND MEDICINE

2008 ◽  
Vol 01 (01) ◽  
pp. 71-83 ◽  
Author(s):  
AVRAHAM MAYEVSKY
Keyword(s):  
Blood Flow ◽  
Real Time ◽  
Mitochondrial Function ◽  
Foley Catheter ◽  
The Body ◽  
Tissue Blood Flow ◽  
Mitochondrial Activity ◽  
New Device ◽  
Urethral Wall

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.

scholarly journals Oxygen Homeostasis and Mitochondrial Function in COVID-19 and ARDS Patients: The Ultimate Vital Signs

2020 ◽  
Keyword(s):  
Blood Flow ◽  
Real Time ◽  
Mitochondrial Function ◽  
Vital Signs ◽  
The Body ◽  
Oxygen Balance ◽  
Tissue Oxygen ◽  
Microcirculatory Blood Flow ◽  
Oxygen Homeostasis ◽  
Hemoglobin Oxygenation

The leading cause of death from the COVID-19 is the development of Pneumonia and Acute Respiratory Distress Syndrome-ARDS. Advanced physiological monitoring of COVID -19 patients in real time is a missing tool that avoid the optimization of better diagnosis and evaluating the efficacy of the treatment given. As of today, the monitoring of the systemic vital signs provides important information regarding the respiratory and cardiovascular systems including the pulse oximetry that provide data on hemoglobin oxygenation in the macro circulation. Our hypothesis is that the pathophysiology of COVID-19 and ARDS patients includes severe changes in the microcirculatory hemodynamics and cellular disturbances in Tissue and cellular Oxygen Homeostasis. Therefore, we postulate that real time monitoring of mitochondrial NADH redox state and microcirculatory blood flow, volume and hemoglobin oxygenation is the missing information that will affect dramatically the outcome of COVID-19 and ARDS patients. During the last 2 decades we studied the mechanism of blood flow redistribution activated in animal models as well as in patients exposed to total body negative oxygen balance. This mechanism is activated by the sympathetic pathway. This effect is not equal in all organs of the body, namely, in the most vital organs - brain, heart, and adrenal glands oxygen supply is preserved while in the less vital organs (visceral and peripheral organs) hypo perfusion and negative oxygen balance is recorded. In order to evaluate the tissue oxygen homeostasis, we developed a new concept named - LifenLight Score (LLS)TM based on the monitoring of four physiological parameters measured in real time from one of the less vital organs in the body. Our developed device is monitoring mitochondrial function by measuring the NADH auto fluorescence and microcirculatory blood flow, tissue reflectance and hemoglobin oxygenation. In animal model we monitored simultaneously the brain and the small intestine. In patients we used a 3-way Foley catheter introduced to the bladder via the urethra. We found that monitoring the less vital organ could serve as an early warning signal to the development of negative oxygen balance in the body as well as indicate of a recovery process in the improvement of the oxygen balance homeostasis. In conclusion, we hypothesize that using our new monitoring system will be able to detect deterioration process related to hypoxia in COVID-19 and ARDS patients, as well as to monitor improvement in tissue oxygen balance due to various treatments such as exposure to hyperoxia.

Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies

2007 ◽  
Vol 292 (2) ◽  
pp. C615-C640 ◽  
Author(s):  
Avraham Mayevsky ◽  
Gennady G. Rogatsky
Keyword(s):  
Animal Models ◽  
Real Time ◽  
Mitochondrial Function ◽  
The Body ◽  
Patient Treatment ◽  
Metabolic State ◽  
Experimental Conditions ◽  
Fluorescence Measurements ◽  
Nadh Fluorescence

Normal mitochondrial function is a critical factor in maintaining cellular homeostasis in various organs of the body. Due to the involvement of mitochondrial dysfunction in many pathological states, the real-time in vivo monitoring of the mitochondrial metabolic state is crucially important. This type of monitoring in animal models as well as in patients provides real-time data that can help interpret experimental results or optimize patient treatment. The goals of the present review are the following: 1) to provide an historical overview of NADH fluorescence monitoring and its physiological significance; 2) to present the solid scientific ground underlying NADH fluorescence measurements based on published materials; 3) to provide the reader with basic information on the methodologies used in the past and the current state of the art fluorometers; and 4) to clarify the various factors affecting monitored signals, including artifacts. The large numbers of publications by different groups testify to the valuable information gathered in various experimental conditions. The monitoring of NADH levels in the tissue provides the most important information on the metabolic state of the mitochondria in terms of energy production and intracellular oxygen levels. Although NADH signals are not calibrated in absolute units, their trend monitoring is important for the interpretation of physiological or pathological situations. To understand tissue function better, the multiparametric approach has been developed where NADH serves as the key parameter. The development of new light sources in UV and visible spectra has led to the development of small compact units applicable in clinical conditions for better diagnosis of patients.

In vivo real-time visualization of tissue blood flow and angiogenesis using Ag2S quantum dots in the NIR-II window

Biomaterials ◽  
2014 ◽  
Vol 35 (1) ◽  
pp. 393-400 ◽  
Author(s):  
Chunyan Li ◽  
Yejun Zhang ◽  
Mao Wang ◽  
Yan Zhang ◽  
Guangcun Chen ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Blood Flow ◽  
Real Time ◽  
Tissue Blood Flow ◽  
Real Time Visualization ◽  
Ag2s Quantum Dots

Hybrid MPI-MRI System for Dual-Modal In Situ Cardiovascular Assessments of Real-Time 3D Blood Flow Quantification—A Pre-Clinical In Vivo Feasibility Investigation

2020 ◽  
Vol 39 (12) ◽  
pp. 4335-4345
Author(s):  
Jochen Franke ◽  
Nicoleta Baxan ◽  
Heinrich Lehr ◽  
Ulrich Heinen ◽  
Sebastian Reinartz ◽  
...  
Keyword(s):  
Blood Flow ◽  
Real Time ◽  
Flow Quantification ◽  
Blood Flow Quantification

Regional blood flow measurement in vivo for a definable geometry

1964 ◽  
Vol 206 (5) ◽  
pp. 962-966 ◽  
Author(s):  
Marvin B. Bacaner ◽  
James S. Beck
Keyword(s):  
Blood Flow ◽  
Flow Measurement ◽  
Necessary Conditions ◽  
Regional Blood Flow ◽  
The Body ◽  
Continuous Measure ◽  
Radioisotope Method ◽  
Arterial Concentration ◽  
Regional Concentration

A radioisotope method for measuring regional blood flow in the intestine of the dog in vivo has been favorably compared with measurement by timed collection of total venous outflow. The necessary conditions are a continuous measure of arterial concentration and cumulative regional concentration of radioisotope, an experimentally definable region, and temporary complete retention of tracer. The derivation of the relations used suggests additional applications of the method to other regions of the body.

Real-time histology-like video of blood flow concatenated with the original label-free SLAM video collected from in vivo rat mammary tissue

ASVIDE ◽  
2020 ◽  
Vol 7 ◽  
pp. 220-220
Author(s):  
Yi Sun ◽  
Sixian You ◽  
Xiaoxi Du ◽  
Z. George Liu ◽  
Eric J. Chaney ◽  
...  
Keyword(s):  
Blood Flow ◽  
Real Time ◽  
Mammary Tissue ◽  
Label Free ◽  
Original Label

Continuous measurement of tissue blood flow by laser-Doppler spectroscopy

1977 ◽  
Vol 232 (4) ◽  
pp. H441-H448 ◽  
Author(s):  
M. D. Stern ◽  
D. L. Lappe ◽  
P. D. Bowen ◽  
J. E. Chimosky ◽  
G. A. Holloway ◽  
...  
Keyword(s):  
Blood Flow ◽  
Line Width ◽  
Rat Kidney ◽  
Tissue Perfusion ◽  
Laser Doppler ◽  
Renal Physiology ◽  
Tissue Blood Flow ◽  
Outer Cortex ◽  
Promising Tool

Laser light scattered from tissue in vivo is broadened in line width as a result of the Doppler shift produced by moving red cells in the microcirculation. A feasibility study was carried out to demonstrate use of this effect to measure and monitor tissue blood flow. Light from a helium-neon laser illuminated a 1-mm area of tissue (human skin or rat renal cortex), and the backscattered light was detected with a photomultiplier. The spectrum of the Doppler beat notes was analyzed directly with a digital spectrum analyzer, or processed by analog circuitry to yield a flow parameter based on the root-mean-square Doppler line width. This parameter was compared with 133Xe washout in the skin of volunteers subjected to UV-induced erythema and the skin of volunteers subjected to UV-induced erythema and was found to vary in an approximately linear manner with skin blood flow. The laser instrument provided continuous monitoring of blood flow fluctuations, including the pulsatile component. The instrument was used to monitor flow in the outer cortex of the rat kidney during administration of norepinephrine, angiotensin, hydralazine, dextran, dopamine, nitroprusside, and angiotensin blocked by saralasin. Dynamic and steady-state responses were consistent with known pharmacology and renal physiology, and with the assumption that vasoconstrictor angiotensin II receptors in the kidney are accessible to blood-borne inhibitors. The laser-Doppler method is a promising tool for rapid monitoring of dynamic changes in tissue perfusion.

scholarly journals Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bethany Muller ◽  
Niamh Lewis ◽  
Tope Adeniyi ◽  
Henry J. Leese ◽  
Daniel R. Brison ◽  
...  
Keyword(s):  
Real Time ◽  
Oocyte Maturation ◽  
Small Groups ◽  
Mitochondrial Function ◽  
Mitochondrial Activity ◽  
Flux Analysis ◽  
Mammalian Oocyte ◽  
Extracellular Flux ◽  
Early Embryos ◽  
The Impact

AbstractMitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking. Here, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR and its components. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilisation, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration – showing that while activity changes over the course of development in response to physiological demand, the overall efficiency is unchanged. EFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the components of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study mammalian oocyte and embryo metabolism.

Alteration of mitochondrial function in a model of chronic ischemia in vivo in rat heart

2002 ◽  
Vol 282 (3) ◽  
pp. H821-H831 ◽  
Author(s):  
Sihem Boudina ◽  
Muriel N. Laclau ◽  
Liliane Tariosse ◽  
Danièle Daret ◽  
Gérard Gouverneur ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Mitochondrial Function ◽  
Contractile Function ◽  
Systolic Function ◽  
Rate Pressure Product ◽  
Maximal Velocity ◽  
Chronic Ischemia ◽  
Membrane Rupture

The aim of this study was to investigate mitochondrial alterations in an animal model of chronic myocardial ischemia in rats obtained by surgical constriction of the left coronary artery. Resting coronary blood flow was measured using the fluorescent microsphere technique. Contractile function, defined by rate-pressure product, and myocardial oxygen consumption were measured in a Langendorff preparation. The mitochondrial function was evaluated on permeabilized skinned fibers. Three weeks after surgery, ischemic hearts showed a significant decrease in coronary blood flow compared with sham. Hemodynamic measurements showed a significant systolic and diastolic dysfunction. Alterations in mitochondrial function in ischemic hearts were mainly characterized by a significant decrease in the maximal velocity and apparent half-saturation constant for ADP, loss of the stimulatory effect of creatine, and a stimulatory effect of exogenous cytochrome c. These functional alterations were supported by structural alterations characterized by mitochondrial clustering and swelling associated with membrane rupture. We conclude that the alterations in systolic function after chronic ischemia are supported by severe modifications of mitochondrial structure and function.

scholarly journals Mitochondrial function and increased convective O2 transport: implications for the assessment of mitochondrial respiration in vivo

2013 ◽  
Vol 115 (6) ◽  
pp. 803-811 ◽  
Author(s):  
Gwenael Layec ◽  
Luke J. Haseler ◽  
Joel D. Trinity ◽  
Corey R. Hart ◽  
Xin Liu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Near Infrared ◽  
Reactive Hyperemia ◽  
Atp Synthesis ◽  
Synthesis Rate ◽  
Resonance Spectroscopy ◽  
Doppler Ultrasound Imaging

Although phosphorus magnetic resonance spectroscopy (31P-MRS)-based evidence suggests that in vivo peak mitochondrial respiration rate in young untrained adults is limited by the intrinsic mitochondrial capacity of ATP synthesis, it remains unknown whether a large, locally targeted increase in convective O2 delivery would alter this interpretation. Consequently, we examined the effect of superimposing reactive hyperemia (RH), induced by a period of brief ischemia during the last minute of exercise, on oxygen delivery and mitochondrial function in the calf muscle of nine young adults compared with free-flow conditions (FF). To this aim, we used an integrative experimental approach combining 31P-MRS, Doppler ultrasound imaging, and near-infrared spectroscopy. Limb blood flow [area under the curve (AUC), 1.4 ± 0.8 liters in FF and 2.5 ± 0.3 liters in RH, P < 0.01] and convective O2 delivery (AUC, 0.30 ± 0.16 liters in FF and 0.54 ± 0.05 liters in RH, P < 0.01), were significantly increased in RH compared with FF. RH was also associated with significantly higher capillary blood flow ( P < 0.05) and faster tissue reoxygenation mean response times (70 ± 15 s in FF and 24 ± 15 s in RH, P < 0.05). This resulted in a 43% increase in estimated peak mitochondrial ATP synthesis rate (29 ± 13 mM/min in FF and 41 ± 14 mM/min in RH, P < 0.05) whereas the phosphocreatine (PCr) recovery time constant in RH was not significantly different ( P = 0.22). This comprehensive assessment of local skeletal muscle O2 availability and utilization in untrained subjects reveals that mitochondrial function, assessed in vivo by 31P-MRS, is limited by convective O2 delivery rather than an intrinsic mitochondrial limitation.

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