Real time monitoring of intraoperative allograft vitality

Journal of Biomedical …, 2011

Background: The involvement of mitochondria in pathological states, such as neurodegenerative diseases, sepsis, stroke, and cancer, are well documented. Monitoring of nicotinamide adenine dinucleotide (NADH) fluorescence in vivo as an intracellular oxygen indicator was established in 1950 to 1970 by Britton Chance and collaborators. We use a multiparametric monitoring system enabling assessment of tissue vitality. In order to use this technology in clinical practice, the commercial developed device, the CritiView (CRV), is tested in animal models as well as in patients. Methods and Results: The new CRV enables the optical monitoring of four different parameters, representing the energy balance of various tissues in vivo. Mitochondrial NADH is measured by surface fluorometry/reflectometry. In addition, tissue microcirculatory blood flow, tissue reflectance and oxygenation are measured as well. The device is tested both in vitro and in vivo in a small animal model and in preliminary clinical trials in patients undergoing vascular or open heart surgery. In patients, the monitoring is started immediately after the insertion of a three-way Foley catheter (urine collection) to the patient and is stopped when the patient is discharged from the operating room. The results show that monitoring the urethral wall vitality provides information in correlation to the surgical procedure performed.

Advances in Biomedical Photonics and Imaging - Proceedings of the 6th International Conference on Photonics and Imaging in Biology and Medicine (PIBM 2007), 2008

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.

SPIE Proceedings, 2008

In normal cell the mitochondria are the major source of energy for cellular functions. They serve as biosensors for oxidative stress and involved also in termination of cell function by apoptosis. The involvement of mitochondria in pathological states such as neurodegenerative diseases, sepsis, stroke and cancer are well documented. The involvement of mitochondrial respiration and function in cancer development, proliferation and possible therapy were initiated 75 years ago by Otto Warburg. Monitoring of NADH fluorescence in vivo as an intracellular oxygen indicator was established in the 1950-1970 by Britton Chance and collaborators. In the last 20 years we developed and used a multiparametric monitoring system enabling real time assessment of mitochondria NADH, microcirculatory blood flow and volume as well as HbO 2 oxygenation. In order to use this technology in clinical practice the commercial developed device-the "CritiView" was tested in animal models as well as in patients hospitalized in the critical care departments. In patients we tested the viability of the urethral wall (a less-vital tissue) by a 3 way Foley urinary catheter that contains the optical probe. The catheter was introduced to patients underwent open heart bypass surgery or abdominal aorta aneurysm (AAA) operations. The monitoring started immediately after the insertion of the catheter to the patient and was stopped when the patient was discharged from the operation room. The results show that monitoring of the vitality of the Urethral wall provides information in correlation to the surgical procedure performed. In the AAA patients the occlusion of the aorta led to severe ischemia developed in the urethral wall and recovery of signals were recorded after the reopening of the aorta. In patients under went heart bypass surgery the urethra vitality was decreased dramatically during the operation and recovery was noted in most patients after the discharge of the patient from the operation room.

Journal of Basic and Clinical Physiology and Pharmacology, 1992

Most current knowledge on events in the mitochondria leading to acute renal failure originates from studies in which indirect methods were used. The disadvantage of these methods is that they cannot measure the turnover rate of various metabolites, and only one result per animal can be obtained. Chance et al. /9/ developed a method using optical techniques for continuously monitoring the fluorescence of intramitochondrial NADH, which has been applied mainly to the brain. This optical method has not yet been examined quantitatively in the kidney and no attempt has been made to adapt this method for routine measurement in kidney tissue. The purpose of this study was to adapt the surface fluorometry method for monitoring renal NADH redox state in situ, and to determine whether the hemodynamic artifacts involved in fluorometric studies of the renal surface in situ could be eliminated by using a correction factor. Another purpose was to understand the relationship between the changes in reflectance and blood volume in the rat kidney. This was achieved by measuring the reflectance after : a) blood exchange by FC-43 emulsion; b) intrarenal saline flush; c) occlusion of the renal vein, renal artery and reopening of the renal vein; d) calculation of the correlation between changes in kidney weight after renal artery occlusion, and the reflectance. Our results suggest that in the rat kidney, as opposed to the brain, a correction factor of 1:1 is not always applicable. This factor may vary between animals, and it is therefore necessary to adjust it electronically for each rat kidney. This observation contradicts the view suggesting a constant correction factor of 1:1 in the kidney. The results reported herein indicate that changes in the reflectance in the ischemic rat kidney are due to changes in blood volume. In conclusion, it seems that optical techniques for monitoring fluorescence are suitable for localized continuous and non-invasive

Microvascular Research, 1998

Hepatic failure is one of the major problems developed during the posttransplantation period. A possible cause of hepatic failure is the prolonged ischemia induced during the implantation procedure. Hepatic ischemia leads to a reduction in oxygen supply, ATP level decline, liver metabolism impairment, and finally organ failure. The purpose of this study was to estimate the functional state of the liver by monitoring liver blood flow and the mitochondrial NADH redox state simultaneously and continuously during in situ liver ischemia followed by reperfusion. Measurements were performed using the multiprobe developed in our laboratory consisting of fibers for the measurement of relative liver blood flow (laser Doppler flowmetry) and mitochondrial redox state (NADH fluorescence). The experimental procedure included the temporary interruption of blood flow to the liver using three types of ischemia, hepatic artery occlusion, portal vein occlusion, and simultaneous occlusion of hepatic artery and portal vein, followed by a reperfusion period. These preliminary experiments showed a significant decrease in liver blood flow, following the three types of liver ischemia, and a significant increase in NADH levels. The probe used in this study incorporates the advantage of monitoring NADH and liver blood flow simultaneously and continuously from the same area on the surface of the liver. Since each of these two parameters is not calibrated in absolute units, the simultaneous monitoring decreases possible artifacts. Also, it will allow us to determine of the coupling between tissue blood flow and oxidative phosphorylation. It is believed that the measurements of respiratory chain dysfunction might predict organ viability in clinical organ transplantation situations. Using this probe may also help to decrease the variability in liver blood flow monitoring since liver blood flow monitoring is supported simultaneously with the mitochondrial redox state, which supplies the information on liver metabolic and functional state.

Transplantation Proceedings, 2008

Ischemia-reperfusion injury is the major cause of organ dysfunction or even nonfunction following transplantation. It can attenuate the long-term survival of transplanted organs. To evaluate the severity of renal ischemia injury determined by histology, we applied laser-(442 nm and 532 nm) induced fluorescence (LIF), mitochondria respiration, and membrane swelling to evaluate 28 Wistar rats that underwent left kidney warm ischemia for 20, 40, 60, or 80 minutes. LIF performed before ischemia (control) was repeated at 20, 40, 60, and 80 minutes thereafter. We harvested left kidney tissue samples immediately after LIF determination for histology and mitochondrial analyses: state 3 and 4 respiration, respiration control rate (RCR), and membrane swelling. The association of optic spectroscopy with histological damage showed: LIF, 442 nm (r 2 ϭ 0.39, P Ͻ .001) and 532 nm, (r 2 ϭ 0.18, P ϭ .003); reflecting laser/fluorescence-induced, 442 nm (r 2 ϭ 0.20, P ϭ .002) and 532 nm (r 2 ϭ 0.004, P ϭ .67). The associations between mitochondria function and tissue damage were: state 3 respiration (r 2 ϭ 0.43, P ϭ .0004), state 4 respiration (r 2 ϭ 0.03, P ϭ 0.38), RCR (r 2 ϭ 0.28, P ϭ .007), and membrane swelling (r 2 ϭ 0.02, P ϭ .43). The intensity of fluorescence emitted by tissue excited by laser, especially at a wave length of 442 nm, was determined in real time. Mitochondrial state 3 respiration and respiratory control ratio also exhibited good correlations with the grade of ischemic tissue damage.

Journal of Clinical Monitoring and Computing, 2012

Monitoring the mitochondrial function, alone or together with microcirculatory blood flow, volume and hemoglobin oxygenation in patients, is very rare. The integrity of microcirculation and mitochondrial activity is a key factor in keeping normal cellular activities. Many pathological conditions in patients are directly or indirectly related to dysfunction of the mitochondria. Evaluation of mitochondrial activity by measuring the autofluorescence of NADH has been the most practical approach since the 1950s. This review, which accompanies part I, presents the principles and technological aspects of various devices used in order to monitor mitochondrial NADH redox state and tissue viability in patients. In part I, the detailed technological aspects of NADH monitoring were described. Typical results accumulated in our studies since the mid-1990s are presented as well. We were able to apply the fiber optic based NADH fluorometry to several organs monitored in vivo in patients under various pathophysiological conditions.

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