Tissue oxygen saturation during hyperthermic progressive central hypovolemia.

During normothermia, a reduction in near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation (So2) is an indicator of central hypovolemia. Hyperthermia increases skin blood flow and reduces tolerance to central hypovolemia, both of which may alter the interpretation of tissue So2 during central hypovolemia. This study tested the hypothesis that maximal reductions in tissue So2 would be similar throughout normothermic and hyperthermic central hypovolemia to presyncope. Ten healthy males (means ± SD; 32 ± 5 yr) underwent central hypovolemia via progressive lower-body negative pressure (LBNP) to presyncope during normothermia (skin temperature ≈34°C) and hyperthermia (+1.2 ± 0.1°C increase in internal temperature via a water-perfused suit, skin temperature ≈39°C). NIRS-derived forearm (flexor digitorum profundus) tissue So2 was measured throughout and analyzed as the absolute change from pre-LBNP. Hyperthermia reduced (P < 0.001) LBNP tolerance by 49 ± 33% (from 16.7 ± 7.9 to 7.2 ± 3.9 min). Pre-LBNP, tissue So2 was similar (P = 0.654) between normothermia (74 ± 5%) and hyperthermia (73 ± 7%). Tissue So2 decreased (P < 0.001) throughout LBNP, but the reduction from pre-LBNP to presyncope was greater during normothermia (-10 ± 6%) than during hyperthermia (-6 ± 5%; P = 0.041). Contrary to our hypothesis, these findings indicate that hyperthermia is associated with a smaller maximal reduction in tissue So2 during central hypovolemia to presyncope.

Near infrared spectroscopy-derived interstitial hydrogen ion concentration and tissue oxygen saturation during ambulation.

The objective of this study was to determine whether walking and running at different treadmill speeds resulted in different metabolic and cardiovascular responses in the vastus lateralis (VL) and lateral gastrocnemius (LG) by examining metabolite accumulation and tissue oxygen saturation. Ten healthy subjects (6 males, 4 females) completed a submaximal treadmill exercise test, beginning at 3.2 km h(-1) and increasing by 1.6 km h(-1) increments every 3 min until reaching 85% of age-predicted maximal heart rate. Muscle tissue oxygenation (SO(2)), total hemoglobin (HbT) and interstitial hydrogen ion concentration ([H(+)]) were calculated from near infrared spectra collected from VL and LG. The [H(+)] threshold for each muscle was determined using a simultaneous bilinear regression. Muscle and treadmill speed effects were analyzed using a linear mixed model analysis. Paired t-tests were used to test for differences between muscles in the [H(+)] threshold. SO(2) decreased (P = 0.001) during running in the VL and LG, but the SO(2) response across treadmill speeds was different between muscles (P = 0.047). In both muscles, HbT and [H(+)] increased as treadmill speed increased (P < 0.001), but the response to exercise was not different between muscles. The [H(+)] threshold occurred at a lower whole-body VO(2) in the LG (1.22 ± 0.63 L min(-1)) than in the VL (1.46 ± 0.58 L min(-1), P = 0.01). In conclusion, interstitial [H(+)] and SO(2) are aggregate measures of local metabolite production and the cardiovascular response. Inferred from simultaneous SO(2) and [H(+)] measures in the VL and LG muscles, muscle perfusion is well matched to VL and LG work during walking, but not running.

Oxygen saturation determined from deep muscle, not thenar tissue, is an early indicator of central hypovolemia in humans.

OBJECTIVE: To compare the responses of noninvasively measured tissue oxygen saturation (StO2) and calculated muscle oxygen tension (PmO2) to standard hemodynamic variables for early detection of imminent hemodynamic instability during progressive central hypovolemia in humans. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Sixteen healthy human volunteers. INTERVENTIONS: Progressive lower body negative pressure (LBNP) to onset of cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Noninvasive measurements of blood pressures, heart rate, and stroke volume were obtained during progressive LBNP with simultaneous assessments of StO2, PmO2, and muscle oxygen saturation (SmO2). Forearm SmO2 and PmO2 were determined with a novel near infrared spectroscopic measurement device (UMMS) and compared with thenar StO2 measured by a commercial device (HT). All values were normalized to the duration of LBNP exposure required for cardiovascular collapse in each subject (i.e., LBNP maximum). Stroke volume was significantly decreased at 25% of LBNP maximum, whereas blood pressure was a late indicator of imminent cardiovascular collapse. PmO2 (UMMS) was significantly decreased at 50% of maximum LBNP while SmO2 (UMMS) decreased at 75% of maximum LBNP. Thenar StO2 (HT) showed no statistical change throughout the entire LBNP protocol. CONCLUSIONS: Spectroscopic assessment of forearm muscle PO2 and SmO2 provides noninvasive and continuous measures that are early indicators of impending cardiovascular collapse resulting from progressive reductions in central blood volume.

Noninvasive determination of exercise-induced hydrodgen ion threshold through direct optical measurement.

The intensity of exercise above which oxygen uptake (Vo2) does not account for all of the required energy to perform work has been associated with lactate accumulation in the blood (lactate threshold, LT) and elevated carbon dioxide output (gas exchange threshold). An increase in hydrogen ion concentration ([H+]) is approximately concurrent with elevation of blood lactate and CO2 output during exercise. Near-infrared spectra (NIRS) and invasive interstitial fluid pH (pHm) were measured in the flexor digitorum profundus during handgrip exercise to produce a mathematical model relating the two measures with an estimated error of 0.035 pH units. This NIRS pHm model was subsequently applied to spectra collected from the vastus lateralis of 10 subjects performing an incremental-intensity cycle protocol. Muscle oxygen saturation (SmO2) was also calculated from spectra. We hypothesized that a H+ threshold could be identified for these subjects and that it would be different from but correlated with the LT. Lactate, gas exchange, SmO2, and H+ thresholds were determined as a function of Vo2 using bilinear regression. LT was significantly different from both the gas exchange threshold (Delta = 0.27 +/- 0.29 l/min) and H+ threshold (Delta = 0.29 +/- 0.23 l/min), but the gas exchange threshold was not significantly different from the H+ threshold (Delta = 0.00 +/- 0.38 l/min). The H+ threshold was strongly correlated with LT (R2 = 0.95) and the gas exchange threshold (R2 = 0.85). This initial study demonstrates the feasibility of noninvasive pHm estimations, the determination of H+ threshold, and the relationship between H+ and classical metabolic thresholds during incremental exercise.

Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans.

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2 and SV were significantly decreased during the first LBNP level (-15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.

Quantitative measurement of muscle oxygen saturation without influence from skin and fat using continuous-wave near infrared spectroscopy.

A method to non-invasively and quantitatively measure muscle oxygen saturation (SmO(2)) using broadband continuous-wave diffuse reflectance near infrared (NIR) spectroscopy is presented. The method obtained SmO(2) by first correcting NIR spectra for absorption and scattering of skin pigment and fat, then fitting to a Taylor expansion attenuation model. A non-linear least squares optimization algorithm with set boundary constraints on the fitting parameters was used to fit the model to the acquired spectra. A data preprocessing/optimization scheme for accurately determining the initial values needed for the optimization was also employed. The method was evaluated on simulated muscle spectra with 4 different scattering properties, as well as on in vivo forearm spectra from 5 healthy volunteer subjects during arterial occlusion. Measurement repeatability was assessed on 24 healthy volunteers with 5 repeated measurements, each separated by at least 48 hours.

Noninvasive in vivo measurement of venous blood pH during exercise using near-infrared reflectance spectroscopy.

Blood pH is an important indicator of anaerobic metabolism in exercising muscle. This paper demonstrates multivariate calibration techniques that can be used to produce a general pH model that can be applied to spectra from any new subject without significant prediction error. Tissue spectra (725 approximately 880 nm) were acquired through the skin overlying the flexor digitorum profundus muscle on the forearms of eight healthy subjects during repetitive hand-grip exercise and referenced to the pH of venous blood drawn from a catheter placed in a vein close to the muscle. Calibration models were developed using multi-subject partial least squares (PLS) and validated using subject-out cross-validation after the subject-to-subject spectral variations were corrected by mathematical preprocessing methods. A combination of standard normal variate (SNV) scaling and principal component analysis loading correction (PCALC) successfully removed most of the subject-to-subject variations and provided the most accurate prediction results.

Comparison of intramuscular and venous blood pH, PCO(2) and PO(2) during rhythmic handgrip exercise.

Oxygen and acid-base status during exercise is well established for the lungs, large arteries and veins. However, values for these parameters in exercising muscle are less frequently reported. In this study we examined the relationship between intramuscular PO(2), pH, PCO(2) and the comparable venous values during rhythmic isometric handgrip exercise at target levels of 15%, 30% and 45% of maximum voluntary contraction (MVC). A small fiber optic sensor was inserted into the flexor digitorum profundus (FDP) muscle for continuous measurement of intramuscular (IM) PO(2), pH and PCO(2). Venous blood samples were taken from the forearm every minute during each exercise bout. IM pH and PCO(2) were similar to their venous counterparts at baseline, but the difference between IM and venous values increased when exercise exceeded 30% MVC. During exercise at 15% MVC and greater, venous PO(2) declined from 40 to 21 Torr (approximately 5.3 to 2.8 kPa). IM PO(2) declined from 24 to 8 Torr with 15% MVC, and approached 0 Torr at 30% MVC and 45% MVC. IM pH declined rapidly when IM PO(2) reached 10 Torr and continued to decrease with increasing exertion, despite an IM PO(2) near 0 Torr.

Removal of analyte-irrelevant variations in near-infrared tissue spectra.

This paper describes mathematical techniques to correct for analyte-irrelevant optical variability in tissue spectra by combining multiple preprocessing techniques to address variability in spectral properties of tissue overlying and within the muscle. A mathematical preprocessing method called principal component analysis (PCA) loading correction is discussed for removal of inter-subject, analyte-irrelevant variations in muscle scattering from continuous-wave diffuse reflectance near-infrared (NIR) spectra. The correction is completed by orthogonalizing spectra to a set of loading vectors of the principal components obtained from principal component analysis of spectra with the same analyte value, across different subjects in the calibration set. Once the loading vectors are obtained, no knowledge of analyte values is required for future spectral correction. The method was tested on tissue-like, three-layer phantoms using partial least squares (PLS) regression to predict the absorber concentration in the phantom muscle layer from the NIR spectra. Two other mathematical methods, short-distance correction to remove spectral interference from skin and fat layers and standard normal variate scaling, were also applied and/or combined with the proposed method prior to the PLS analysis. Each of the preprocessing methods improved model prediction and/or reduced model complexity. The combination of the three preprocessing methods provided the most accurate prediction results. We also performed a preliminary validation on in vivo human tissue spectra.

The efficacy of novel anatomical sites for the assessment of muscle oxygenation during central hypovolemia.

Muscle tissue oxygenation (SmO2) can track central blood volume loss associated with hemorrhage. Traditional peripheral measurement sites (e.g., forearm) may not be practical due to excessive movement or injury (e.g., amputation). The aim of this study was to evaluate the efficacy of three novel anatomical sites for the assessment of SmO2 under progressive central hypovolemia. 10 male volunteers were exposed to stepwise prone lower body negative pressure to decrease central blood volume, while SmO2 was assessed at four sites-the traditional site of the flexor carpi ulnaris (ARM), and three novel sites not previously investigated during lower body negative pressure, the deltoid, latissimus dorsi, and trapezius. SmO2 at the novel sites was compared to the ARM sensor and to stroke volume responses. A reduction in SmO2 was detected by the ARM sensor at the first level of lower body negative pressure (-15 mmHg; P = 0.007), and at -30 (the deltoid), -45 (latissimus dorsi), and -60 mmHg lower body negative pressure (trapezius) at the novel sites (P ≤ 0.04). SmO2 responses at all novel sites were correlated with responses at the ARM (R ≥ 0.89), and tracked the reduction in stroke volume (R ≥ 0.87); the latissimus dorsi site exhibited the strongest linear correlations (R ≥ 0.96). Of the novel sensor sites, the latissimus dorsi exhibited the strongest linear associations with SmO2 at the ARM, and with reductions in central blood volume. These findings have important implications for detection of hemorrhage in austere environments (e.g., combat) when use of a peripheral sensor may not be ideal, and may facilitate incorporation of these sensors into uniforms.

Influence of a fat layer on the near infrared spectra of human muscle: quantitative analysis based on two-layered Monte Carlo simulations and phantom experiments.

The influence of fat thickness on the diffuse reflectance spectra of muscle in the near infrared (NIR) region is studied by Monte Carlo simulations of a two-layer structure and with phantom experiments. A polynomial relationship was established between the fat thickness and the detected diffuse reflectance. The influence of a range of optical coefficients (absorption and reduced scattering) for fat and muscle over the known range of human physiological values was also investigated. Subject-to-subject variation in the fat optical coefficients and thickness can be ignored if the fat thickness is less than 5 mm. A method was proposed to correct the fat thickness influence.

Skin color correction for tissue spectroscopy: demonstration of a novel approach with tissue-mimicking phantoms.

The application of partial least squares (PLS) regression to visible-near-infrared (VIS-NIR) spectroscopy for modeling important blood and tissue parameters is generally complicated by the variation in skin pigmentation (melanin) across the human population. An orthogonal correction method for removing the influence of skin pigmentation has been demonstrated in diffuse reflectance spectra from two-layer tissue-mimicking phantoms. The absorption properties of the phantoms were defined by lyophilized human hemoglobin (bottom layer) and synthetic melanin (top layer). Tissue-like scattering was simulated in both layers with intralipid. The approach uses principal components analysis (PCA) loading vectors from a separate set of phantom spectra that encode the unwanted melanin variation to remove the effect of melanin from the test phantoms. The preprocessing of phantom spectra using this orthogonal correction method resulted in PLS models with reduced complexity and enhanced prediction performance. Preliminary results from a separate study that evaluates the feasibility of defining skin color variation in an experiment with a single human subject are also presented.

Smart medical systems with application to nutrition and fitness in space.

Smart medical systems are being developed to allow medical treatments to address alterations in chemical and physiologic status in real time. In a smart medical system, sensor arrays assess subject status, which is interpreted by computer processors that analyze multiple inputs and recommend treatment interventions. The response of the subject to the treatment is again assessed by the sensor arrays, thus closing the loop. An early form of "smart medicine" has been practiced in space to assess nutrition. Nutrient levels are assessed with food frequency questionnaires, which are interpreted by flight surgeons to recommend inflight alterations in diet. In the future, sensor arrays will directly probe body chemistry. Near-infrared spectroscopy can be used to non-invasively measure several blood and tissue parameters that are important in the assessment of nutrition and fitness. In particular, this technology can be used to measure blood hematocrit and interstitial fluid pH. The non-invasive measurement of interstitial pH is discussed as a surrogate for blood lactate measurement for the development and real-time assessment of exercise protocols in space. Earth-based application of these sensors is also described.

Investigation of electrolyte measurement in diluted whole blood using spectroscopic and chemometric methods.

The feasibility of using near-infrared (NIR) spectroscopy in combination with partial least-squares (PLS) regression was explored to measure electrolyte concentration in whole blood samples. Spectra were collected from diluted blood samples containing randomized, clinically relevant concentrations of Na+, K+, and Ca2+. Sodium was also studied in lysed blood. Reference measurements were made from the same samples using a standard clinical chemistry instrument. Partial least squares (PLS) was used to develop calibration models for each ion with acceptable results (Na+, R2 = 0.86, CVSEP = 9.5 mmol/L; K+, R2 = 0.54, CVSEP = 1.4 mmol/L; Ca2+, R2 = 0.56, CVSEP = 0.18 mmol/L). Slightly improved results were obtained using a narrower wavelength region (470-925 nm) where hemoglobin, but not water, absorbed indicating that ionic interaction with hemoglobin is as effective as water in causing measurable spectral variation. Good models were also achieved for sodium in lysed blood, illustrating that cell swelling, which is correlated with sodium concentration, is not required for calibration model development.

Experimental coronary artery occlusion: relevance to off-pump cardiac surgery.

Mechanical coronary artery occlusion is required for minimally invasive direct coronary artery bypass and off-pump coronary artery bypass surgery. It is important that the method of occlusion be minimally traumatic. Chronic effects of these methods have never been studied. Temporary occlusion of coronaries utilizing suture snare, silastic loop snare, and bulldog clamp was carried out in 12 Yucatan pigs. Three animals each were sacrificed acutely and at 3, 6, and 12 months. The area of occlusion of each vessel was examined by light microscopy and the degree of damage recorded. In the animals sacrificed acutely, there was more damage using the suture snare than with the other 2 methods, but there was minimal damage at longer intervals. There was slight damage acutely and chronically with the bulldog technique. No damage was seen acutely with the silastic loop technique, but some late damage was found. The techniques of coronary artery dissection and occlusion used for minimally invasive and off-pump bypass surgery may contribute to early postoperative graft occlusion.

Lightweight noninvasive trauma monitor for early indication of central hypovolemia and tissue acidosis: a review.

BACKGROUND: Hemorrhage is a major cause of soldier death; it must be quickly identified and appropriately treated. We developed a prototype patient monitor that noninvasively and continuously determines muscle oxygen saturation (SmO2), muscle pH (pHm), and a regional assessment of blood volume (HbT) using near-infrared spectroscopy. Previous demonstration in a model of progressive, central hypovolemia induced by lower body negative pressure (LBNP) showed that SmO2 provided an early indication of impending hemodynamic instability in humans. In this review, we expand the number of subjects and provide an overview of the relationship between the muscle and sublingual microcirculation in this model of compensated shock. METHODS: Healthy human volunteers (n = 30) underwent progressive LBNP in 5-minute intervals. Standard vital signs, along with stroke volume (SV), total peripheral resistance, functional capillary density, SmO2, HbT, and pHm were measured continuously throughout the study. RESULTS AND DISCUSSION: SmO2 and SV significantly decreased during the first level of central hypovolemia (-15 mm Hg LBNP), whereas vital signs were later indicators of impending cardiovascular collapse. SmO2 declined with SV and inversely with total peripheral resistance throughout LBNP. HbT was correlated with declining functional capillary density, suggesting vasoconstriction as a cause for decreased SmO2 and subsequently decreased pHm. CLINICAL TRANSLATION: The monitor has been miniaturized to a 58-g solid-state sensor that is currently being evaluated on patients with dengue hemorrhagic fever. Early results demonstrate significant decreases in SmO2 similar to those observed with progressive reductions in central blood volume. As such, this technology has the potential to (1) provide a monitoring capability for both nontraumatic and traumatic hemorrhage and (2) help combat medics triage casualties and monitor patients during lengthy transport from combat areas.

Oxygen transport characterization of a human model of progressive hemorrhage.

BACKGROUND: Hemorrhage continues to be a leading cause of death from trauma sustained both in combat and in the civilian setting. New models of hemorrhage may add value in both improving our understanding of the physiologic responses to severe bleeding and as platforms to develop and test new monitoring and therapeutic techniques. We examined changes in oxygen transport produced by central volume redistribution in humans using lower body negative pressure (LBNP) as a potential mimetic of hemorrhage. METHODS AND RESULTS: In 20 healthy volunteers, systemic oxygen delivery and oxygen consumption, skeletal muscle oxygenation and oral mucosa perfusion were measured over increasing levels of LBNP to the point of hemodynamic decompensation. With sequential reductions in central blood volume, progressive reductions in oxygen delivery and tissue oxygenation and perfusion parameters were noted, while no changes were observed in systemic oxygen uptake or markers of anaerobic metabolism in the blood (e.g., lactate, base excess). While blood pressure decreased and heart rate increased during LBNP, these changes occurred later than the reductions in tissue oxygenation and perfusion. CONCLUSIONS: These findings indicate that LBNP induces changes in oxygen transport consistent with the compensatory phase of hemorrhage, but that a frank state of shock (delivery-dependent oxygen consumption) does not occur. LBNP may therefore serve as a model to better understand a variety of compensatory physiological changes that occur during the pre-shock phase of hemorrhage in conscious humans. As such, LBNP may be a useful platform from which to develop and test new monitoring capabilities for identifying the need for intervention during the early phases of hemorrhage to prevent a patient's progression to overt shock.

Simultaneous correction of the influence of skin color and fat on tissue spectroscopy by use of a two-distance fiber-optic probe and orthogonalization technique.

We have demonstrated simultaneous correction for the optical interference of skin and fat in tissue spectra by using a two-distance fiber-optic probe. We obtained the correction by orthogonalizing the spectra collected at a long source-detector distance (SD) to the spectra collected at a short SD and mapped to the long SD space. The method was validated in tissuelike three-layer phantoms as well as preliminarily in human tissue. After the correction, a partial-least-squares model of the phantoms showed enhanced prediction performance.

Investigation of muscle pH as an indicator of liver pH and injury from hemorrhagic shock.

BACKGROUND: During hemorrhagic shock blood flow to vital organs is maintained by the diversion of blood from both the splanchnic organs and skeletal muscle. In this swine study, we tested the hypotheses that (1). liver and muscle pH are correlated during both shock and resuscitation and (2). muscle pH during shock is an indicator of potential liver injury after resuscitation. MATERIALS AND METHODS: Hemorrhagic shock was induced over 15 min to lower systolic blood pressure to 40 mm Hg and was maintained for 60 (n = 5) or 90 (n = 5) min. Resuscitation was achieved with shed blood and warm saline to maintain mean pressure >60 mm Hg for 120 min. Liver and muscle pH were measured with microelectrodes throughout the entire shock and resuscitation periods, along with hepatic venous oxygen saturation. Arterial lactate and aspartate aminotransferase were measured at baseline, end of shock, and resuscitation. Correlation between muscle and liver pH was determined. The ability of muscle pH to predict liver injury (40% increase in arterial aspartate aminotransferase) was compared with other predictors: liver pH, arterial lactate, and tonometric-arterial PCO(2) gap. RESULTS: pH values and rates of change were similar in both muscle and liver tissue. Liver pH was well correlated with muscle pH during both shock and resuscitation, R(2) = 0.84. Muscle pH predicts potential liver injury with the same sensitivity as blood lactate in this swine shock model. CONCLUSIONS: Minimally invasive measurement of muscle pH warrants further study as a method to assess splanchnic hypoperfusion and resultant injury.