Kenneth A Schenkman's research while affiliated with University of Washington Seattle and other places

Publications (41)

Article
In critically ill patients, direct knowledge of intracellular pO 2 would allow for identification of cellular hypoxia, which when prolonged leads to organ failure. We have developed a visible–near-infrared optical system that noninvasively measures myoglobin saturation, which is directly related to intracellular pO 2 , from the surface of the skin....
Article
Full-text available
Background Adaptive responses to congenital heart disease (CHD) result in altered muscle perfusion and muscle metabolism. Such changes may be detectable using noninvasive spectroscopic monitors. Aim In this study we aimed to determine if resting muscle oxygen saturation (MOx) is lower in children with acyanotic or cyanotic CHD than in healthy chil...
Article
Full-text available
Purpose The aim of this pilot study was to evaluate the potential of a new noninvasive optical measurement of muscle oxygenation (MOx) to identify shock severity in patients with suspected sepsis. Methods We enrolled 51 adult patients in the emergency department (ED) who presented with possible sepsis using traditional Systematic Inflammatory Resp...
Article
Objective: To assess the potential utility of a novel non-invasive muscle oxygen measurement to determine the presence of muscle hypoxia in patients with anaemia. Background: Recent assessment of the risk/benefit ratio of blood transfusion has led to clinical strategies optimising transfusion decisions. These decisions are primarily based on hae...
Article
Introduction: We evaluated the potential utility of a new prototype noninvasive muscle oxygenation (MOx) measurement for the identification of shock severity in a population of patients admitted to the trauma resuscitation rooms of a Level I regional trauma center. The goal of this project was to correlate MOx with shock severity as defined by sta...
Article
Full-text available
Optical spectroscopy is being used increasingly in medical applications to noninvasively investigate tissues below the skin. In order to assure adequate sampling of tissues underlying the skin, photon penetration depth must be known. Photon penetration in tissues has been studied with near-infrared (NIR) light, but experimental study of visible lig...
Article
We have developed a method to make real-time, continuous, noninvasive measurements of muscle oxygenation (Mox) from the surface of the skin. A key development was measurement in both the visible and near infrared (NIR) regions. Measurement of both oxygenated and deoxygenated myoglobin and hemoglobin resulted in a more accurate measurement of Mox th...
Article
This study demonstrates use of novel technology to measure cellular oxygenation during corrective congenital heart surgery. Cellular oxygenation was measured using a custom-designed optical probe placed on the free wall of the right ventricle. Cellular oxygenation, determined from myoglobin saturation, was calculated using multiwavelength analysis....
Article
A method to simultaneously measure oxygenation in vascular, intracellular, and mitochondrial spaces from optical spectra acquired from muscle has been developed. In order to validate the method, optical spectra in the visible and near-infrared regions (600-850 nm) were acquired from solutions of myoglobin, hemoglobin, and cytochrome oxidase that in...
Article
Mitochondria integrate the key metabolic fluxes in the cell. This role places this organelle at the center of cellular energetics and, hence, mitochondrial dysfunction underlies a growing number of human disorders and age-related degenerative diseases. Here we present novel analytical and technical methods for evaluating mitochondrial metabolism an...
Article
To study effects of mitochondrial complex I (CI, NADH:ubiquinone oxidoreductase) deficiency, we inactivated the Ndufs4 gene, which encodes an 18 kDa subunit of the 45-protein CI complex. Although small, Ndufs4 knockout (KO) mice appeared healthy until approximately 5 weeks of age, when ataxic signs began, progressing to death at approximately 7 wee...
Article
The ability to quantify the contributions of hemoglobin (Hb) and myoglobin (Mb) to in vivo optical spectra has many applications for clinical and research use such as noninvasive measurement of local tissue O(2) uptake rates and regional blood content. Recent work has demonstrated an approach to independently measure oxygen saturations of Hb and Mb...
Article
Recent clinical studies of patients with sepsis have shown that the delivery of adequate oxygen alone does not necessarily result in improved organ function or survival. This study was undertaken to determine if optical spectroscopy could detect higher intracellular oxygenations in isolated, perfused guinea pig hearts that have been treated with en...
Article
Cerebral edema associated with diabetic ketoacidosis is an uncommon but severe complication of insulin-dependent diabetes mellitus with unclear pathophysiology. We sought to determine whether cerebral edema in patients with diabetic ketoacidosis was related to changes in cerebral blood flow, autoregulation, regional cerebral saturation, or S100B. P...
Article
To observe the effects of right carotid artery ligation and variations in extracorporeal life support (ECLS) flow on regional cerebral oxygenation index (rSO2i) measured using near infrared spectroscopy. Prospective observational study. Tertiary children's hospital. Eleven neonatal and pediatric patients requiring veno-arterial ECLS support between...
Article
The mitochondrial theory of ageing proposes that the accumulation of oxidative damage to mitochondria leads to mitochondrial dysfunction and tissue degeneration with age. However, no consensus has emerged regarding the effects of ageing on mitochondrial function, particularly for mitochondrial coupling (P/O). One of the main barriers to a better un...
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Full-text available
Previous work from this laboratory using near-infrared optical spectroscopy of myoglobin has shown that approximately 20% of the myocardium is hypoxic in buffer-perfused hearts that are perfused with fully oxygenated buffer at 37 degrees C. The present study was undertaken to determine cardiac myoglobin saturation in buffer-perfused hearts when car...
Article
Myoglobin is an important intracellular oxygen transport molecule in muscle. Oxygen binding to myoglobin can be determined spectroscopically due to differences in absorption of oxymyoglobin and deoxymyoglobin. Myoglobin oxygenation can be used as a measure of intracellular oxygen tension in muscle. We sought to determine the effects of differences...
Article
The coupling of mitochondrial ATP synthesis and oxygen consumption (ratio of ATP and oxygen fluxes, P/O) plays a central role in cellular bioenergetics. Reduced P/O values are associated with mitochondrial pathologies that can lead to reduced capacity for ATP synthesis and tissue degeneration. Previous work found a wide range of values for P/O in n...
Article
Myocardial mean myoglobin oxygen saturation was determined spectroscopically from isolated guinea pig hearts perfused with red blood cells during increasing hypoxia. These experiments were undertaken to compare intracellular myoglobin oxygen saturation in isolated hearts perfused with a modest concentration of red blood cells (5% hematocrit) with i...
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Full-text available
In skeletal muscle, intracellular Po2 can fall to as low as 2-3 mmHg. This study tested whether oxygen regulates cellular respiration in this range of oxygen tensions through direct coupling between phosphorylation potential and intracellular Po2. Oxygen may also behave as a simple substrate in cellular respiration that is near saturating levels ov...
Article
An anatomically realistic model for oxygen transport in cardiac tissue is introduced for analyzing data measured from isolated perfused guinea pig hearts. The model is constructed to match the microvascular anatomy of cardiac tissue based on available morphometric data. Transport in the three-dimensional system (divided into distinct microvascular,...
Article
Accurate myoglobin oxygen saturation determination from tissue using optical spectral analysis has been limited by overlap in spectral features between myoglobin and hemoglobin. Partial least-squares analysis of reflectance spectra has been successfully used to predict myoglobin oxygen saturation from blood perfused hearts, although uncertainty rem...
Article
Voltage-gated sodium channels composed of pore-forming alpha and auxiliary beta subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of distinct sodium channel subtypes have not been clearly defined. Immunocytochemical studies show that the principal cardiac pore-forming alpha subunit iso...
Article
The rate of oxygen consumption is an important measure of mitochondrial function in all aerobic cells. In pancreatic beta cells, it is linked to the transduction mechanism that mediates glucose-stimulated insulin secretion. However, measurement of oxygen consumption over long periods of time is technically difficult owing to the error resulting fro...
Article
Critical intracellular myocardial oxygen tension was determined by optical spectroscopic measurement of myoglobin oxygen saturation in crystalloid-perfused guinea pig hearts. Accurate end-point determinations of the maximally oxygenated and deoxygenated myoglobin were made. Hearts were subjected to a steady decrease in perfusate oxygen tension whil...
Article
To simultaneously determine the effect of propofol on myocardial oxygenation, mitochondrial function, and whole organ function in an isolated heart model, using optical reflectance spectroscopy. Controlled laboratory investigation. Research laboratory. Twenty adult guinea pigs. Isolated hearts were perfused alternately with a modified oxygenated Kr...
Article
A fiber-optic-based spectrophotometer was developed to acquire optical reflectance spectra from a living dog heart. A bullseye concentric optical probe with a 3 mm source-to-detector fiber separation was designed to obtain a 1.5 mm average tissue depth of light penetration. Spectra were analyzed in the near-infrared region from 660 to 840 nm. Myogl...
Article
Myoglobin is an important intracellular protein found in cardiac and skeletal muscle. It is involved in the intracellular transport of oxygen from the cell membrane to the mitochondria where oxidative phosphorylation takes place. The optical absorbance characteristics of myoglobin are similar to those of hemoglobin in the nearinfrared spectral regi...
Article
Multiwavelength optical spectroscopy was used to determine the oxygen-binding characteristics for equine myoglobin. Oxygen-binding relationships as a function of oxygen tension were determined for temperatures of 10, 25, 35, 37, and 40 degrees C, at pH 7.0. In addition, dissociation curves were determined at 37 degrees C for pH 6.5, 7.0, and 7.5. E...
Article
Spectroscopic measurement of myoglobin oxygenation has been made in the presence of hemoglobin using visible light. Although the spectral changes with oxygen binding are smaller, near infrared wavelengths have deeper tissue penetration. This offers an attractive means for making noninvasive muscle oxygenation measurements. Visible and near-infrared...

Citations

... Congenital heart disease (CHD) is the most common congenital defect, characterized by structural abnormalities of the heart or great vessels and affecting 0.82% of live newborns around the world. 1 Cyanotic CHD (CCHD) is one type of CHD and typically characterized by much severer hypoxia, higher mortality, and poorer quality of life. 2,3 The effect of chronic hypoxemia is associated with cardiovascular risks, 4 perioperative bleeding 5 and multisystem damages in the myocardial blood, 6,7 kidney function 8 and retinal microvasculature. 9 Retina is regarded as a window to the heart and can be non-invasively visualized. ...
... Additionally, rSO 2 is a sensitive marker for global cerebral hypoperfusion (13). This study has demonstrated that monitoring of StO 2 is a useful means of clinically evaluating sepsis/septic shock (14,15). ...
... Recently, a definition of massive transfusion that takes into account the use of whole blood was created that identifies early mortality more accurately than other definitions [108]. Although not widely utilized, noninvasive measurement of muscle oxygenation based on optical spectroscopy may provide the most direct measure of shock and is potentially the best indicator with respect to sensitivity and specificity for massive transfusion [109][110][111][112]. ...
... Recently, a definition of massive transfusion that takes into account the use of whole blood was created that identifies early mortality more accurately than other definitions [108]. Although not widely utilized, noninvasive measurement of muscle oxygenation based on optical spectroscopy may provide the most direct measure of shock and is potentially the best indicator with respect to sensitivity and specificity for massive transfusion [109][110][111][112]. ...
... Discussion of these methods can be found elsewhere. 31 In ventilated patients, lung compliance is derived from the volume generated by the set pressure control (PC) level in PC ventilation, and the plateau pressure generated by the set volume target in a flow-controlled ventilation mode. EVLW is measured by the PiCCO system in patients with 2 ventricle physiology and no right-to-left shunt. ...
... Noninvasive vital sign monitoring, which includes measurement of pulse oximetry 18 , capnography, blood pressure (BP) measurement, and the standard five-lead electrocardiogram 19 , has been used for patients who are in the intensive care unit 20 and in the operating room. A stepped frequency continuous wave (SFCW) radar is also used to measure the heart rate and respiration by transmitting high average power pulses with long duration and narrow bandwidth, then a signal-processing algorithm based on the state space method is applied to extract cardiac and respiration rates from the data measured on a human subject using SFCW radar 21 . ...
... NIRS was used on ECMO patients to study the effect of cannulation on cerebral oxygenation. Ligation of RCCA was associated with a decrease in HbO 2 , an increase in HHb [2] and a decrease in tissue oxygen saturation (TOS) [3] while no changes were seen during IJV ligation. Also, an increase in HbO 2 , a decrease in HHb and an increase in TOS was reported after ECMO was established compared to pre-cannulation values. ...
... Measured absorption spectrum reflected the average of undenatured and denatured pigments, which likely broadened the absorption peaks and caused some small shifts in the absorption spectra. In addition, temperature could also cause the shift in myoglobin absorption (Ciesielski, Arakaki, & Schenkman, 2005). Compared to changes in absorption, changes in reduced scattering coefficients were larger at different temperatures suggesting changes in meat structure were induced by heating. ...
... Cytochrome a,a3 is of special interest as this forms the active site for oxygen in complex IV which-as described-forms the first link in the chain of events that lead to IRI [22]. Not surprisingly, due to its diagnostic potential, extensive efforts have gone into attempts to quantify the cytochrome a,a3 redox status using absorbance spectroscopy [23][24][25][26][27]. In whole organs, however, overlap of absorption spectra of different molecules, inhomogeneous tissue scattering, and edema have limited this approach to describing trends rather than direct quantification of the redox status [27][28][29][30]. ...
... Cytochrome a,a3 is of special interest as this forms the active site for oxygen in complex IV which-as described-forms the first link in the chain of events that lead to IRI [22]. Not surprisingly, due to its diagnostic potential, extensive efforts have gone into attempts to quantify the cytochrome a,a3 redox status using absorbance spectroscopy [23][24][25][26][27]. In whole organs, however, overlap of absorption spectra of different molecules, inhomogeneous tissue scattering, and edema have limited this approach to describing trends rather than direct quantification of the redox status [27][28][29][30]. ...