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1.
Appl Spectrosc ; 74(10): 1263-1273, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32662282

ABSTRACT

In critically ill patients, direct knowledge of intracellular pO2 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 pO2, from the surface of the skin. We used an animal model of graded hypoxia from low levels of inspired oxygen (n = 5) and verified that low intracellular pO2 is correlated with high steady-state serum lactate values. In addition, the pO2 gradient between arterial blood and inside muscle cells was 83 mm Hg at 21% O2, but fell to 24 mm Hg at 8% O2. Continuous myoglobin saturation measurement in skeletal muscle displayed the same trends as cerebral oxygenation with no lag in changes over time, demonstrating its relevance as a measure of systemic oxygenation.


Subject(s)
Cell Hypoxia , Muscle, Skeletal/chemistry , Myoglobin/blood , Oxyhemoglobins/analysis , Spectroscopy, Near-Infrared/methods , Animals , Female , Oxygen/blood , Rabbits
2.
Paediatr Anaesth ; 29(8): 850-857, 2019 08.
Article in English | MEDLINE | ID: mdl-31125476

ABSTRACT

BACKGROUND: Adaptive responses to congenital heart disease result in altered muscle perfusion and muscle metabolism. Such changes may be detectable using noninvasive spectroscopic monitors. AIMS: In this study we aimed to determine if resting muscle oxygen saturation (MOx) is lower in children with acyanotic or cyanotic congenital heart disease than in healthy children and to identify differences in muscle oxygen consumption in children with cyanotic and acyanotic congenital heart disease. METHODS: Using a custom fiber optic spectrometer system, optical measurements were obtained from the calf or forearm of 49 patients (17 with acyanotic congenital heart disease, 18 with cyanotic congenital heart disease, and 14 control). Twenty additional control patients were used to develop the analytic model. Spectra were used to determine MOx at baseline, during arterial occlusion, and during reperfusion. The rate of muscle desaturation during arterial occlusion was also evaluated. Two-sample t-tests were used to compare each heart disease group with the controls. RESULTS: Patients with acyanotic and cyanotic congenital heart disease had lower baseline MOx than controls. Baseline MOx was 91.3% (CI 85.9%, 96.7%) for acyanotic patients, 91.1% (CI 86.3%, 95.9%) for cyanotic patients, and 98.9% (CI 96.7%, 101.1%) for controls. Similarly, MOx was lower in the acyanotic and cyanotic groups than the controls after reperfusion (84.6% [CI 74.1%, 95.1%] and 82.1% [CI 74.5%, 89.7%] vs 98.9% [96.5%, 101.3%]). The rate of decline in oxygenation was significantly greater in cyanotic patients versus controls (0.46%/s (CI 0.30%, 0.62%/s) vs 0.17%/s (0.13%, 0.21%/s)). CONCLUSION: This study demonstrates that muscle oxygenation is abnormal in children with both cyanotic and acyanotic congenital heart disease. This suggests that noninvasive monitoring of muscle oxygenation may provide valuable information in situations where children with congenital heart disease may be at risk of hemodynamic compromise.


Subject(s)
Heart Defects, Congenital/metabolism , Heart Defects, Congenital/physiopathology , Oxygen/metabolism , Cyanosis , Female , Humans , Hypoxia/physiopathology , Infant , Male , Respiratory Function Tests
3.
PLoS One ; 12(8): e0182351, 2017.
Article in English | MEDLINE | ID: mdl-28771567

ABSTRACT

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 Response Syndrome criteria or who triggered a "Code Sepsis." Noninvasive MOx measurements were made from the first dorsal interosseous muscles of the hand once potential sepsis/septic shock was identified, as soon as possible after admission to the ED. Shock severity was defined by concurrent systolic blood pressure, heart rate, and serum lactate levels. MOx was also measured in a control group of 17 healthy adults. RESULTS: Mean (± SD) MOx in the healthy control group was 91.0 ± 5.5% (n = 17). Patients with mild, moderate, and severe shock had mean MOx values of 79.4 ± 21.2%, 48.6 ± 28.6%, and 42.2 ± 4.7%, respectively. Mean MOx for the mild and moderate shock severity categories were statistically different from healthy controls and from each other based on two-sample t-tests (p < 0.05). CONCLUSIONS: We demonstrate that noninvasive measurement of MOx was associated with clinical assessment of shock severity in suspected severe sepsis or septic shock. The ability of MOx to detect even mild septic shock has meaningful implications for emergency care, where decisions about triage and therapy must be made quickly and accurately. Future longitudinal studies may validate these findings and the value of MOx in monitoring patient status as treatment is administered.


Subject(s)
Muscle, Skeletal/chemistry , Oxygen/analysis , Sepsis/pathology , Shock, Septic/pathology , Adult , Aged , Blood Pressure , Case-Control Studies , Female , Hand , Heart Rate , Humans , Intensive Care Units , Lactic Acid/blood , Length of Stay , Male , Middle Aged , Muscle, Skeletal/metabolism , Sepsis/metabolism , Severity of Illness Index , Shock, Septic/metabolism , Spectroscopy, Near-Infrared
4.
Shock ; 47(5): 599-605, 2017 05.
Article in English | MEDLINE | ID: mdl-27820776

ABSTRACT

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 standard measures of shock: systolic blood pressure, heart rate, and lactate. METHODS: Optical spectra were collected from subjects by placement of a custom-designed optical probe over the first dorsal interosseous muscles on the back of the hand. Spectra were acquired from trauma patients as soon as possible upon admission to the trauma resuscitation room. Patients with any injury were eligible for study. MOx was determined from the collected optical spectra with a multiwavelength analysis that used both visible and near-infrared regions of light. Shock severity was determined in each patient by a scoring system based on combined degrees of hypotension, tachycardia, and lactate. MOx values of patients in each shock severity group (mild, moderate, and severe) were compared using two-sample t tests. RESULTS: In 17 healthy control patients, the mean MOx value was 91.0 ±â€Š5.5%. A total of 69 trauma patients were studied. Patients classified as having mild shock had a mean MOx of 62.5 ±â€Š26.2% (n = 33), those classified as in moderate shock had a mean MOx of 56.9 ±â€Š26.9% (n = 25) and those classified as in severe shock had a MOx of 31.0 ±â€Š17.1% (n = 11). Mean MOx for each of these groups was statistically different from the healthy control group (P < 0.05).Receiver operating characteristic analyses show that MOx and shock index (heart rate/systolic blood pressure) identified shock similarly well (area under the curves [AUC] = 0.857 and 0.828, respectively). However, MOx identified mild shock better than shock index in the same group of patients (AUC = 0.782 and 0.671, respectively). CONCLUSIONS: The results obtained from this pilot study indicate that MOx correlates with shock severity in a population of trauma patients. Noninvasive and continuous MOx holds promise to aid in patient triage and to evaluate patient condition throughout the course of resuscitation.


Subject(s)
Muscle, Skeletal/blood supply , Oxygen/metabolism , Shock/diagnosis , Wounds and Injuries/diagnosis , Adult , Area Under Curve , Blood Pressure/physiology , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Muscle, Skeletal/metabolism , Oxygen/blood , Oxygen Consumption , Pilot Projects , ROC Curve , Shock/metabolism , Shock/physiopathology , Wounds and Injuries/metabolism , Wounds and Injuries/physiopathology
5.
Anal Chim Acta ; 785: 27-33, 2013 Jun 27.
Article in English | MEDLINE | ID: mdl-23764440

ABSTRACT

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 than could be achieved with measurement of only the deoxygenated components, as in traditional near-infrared spectroscopy (NIRS). Using the second derivative with respect to wavelength reduced the effects of scattering on the spectra and also made oxygenated and deoxygenated forms more distinguishable from each other. Selecting spectral bands where oxygenated and deoxygenated forms absorb filtered out noise and spectral features unrelated to Mox. NIR and visible bands were scaled relative to each other in order to correct for errors introduced by normalization. Multivariate Curve Resolution (MCR) was used to estimate Mox from spectra within each data set collected from healthy subjects. A Locally Weighted Regression (LWR) model was built from calibration set spectra and associated Mox values from 20 subjects using 2562 spectra. LWR and Partial Least Squares (PLS) allow accurate measurement of Mox despite variations in skin pigment or fat layer thickness in different subjects. The method estimated Mox in five healthy subjects with an RMSE of 5.4%.


Subject(s)
Hemoglobins/analysis , Muscles/metabolism , Myoglobin/analysis , Oxygen/chemistry , Spectroscopy, Near-Infrared , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Least-Squares Analysis , Middle Aged , Young Adult
6.
ASAIO J ; 57(4): 314-7, 2011.
Article in English | MEDLINE | ID: mdl-21508828

ABSTRACT

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. Timing of bypass, aortic cross-clamp, infusion of cardioplegic solution, and length of intensive care unit (ICU) stay were recorded. Baseline cellular oxygenation was approximately 50% just before aortic cross-clamp and decreased to approximately 20% during cardioplegia. Cellular oxygenation remained low throughout cardioplegia and returned toward baseline after bypass. In four cases, cellular oxygenation did not return as quickly to baseline as in the other three cases. Among the four patients demonstrating slow recovery, the average ICU length of stay was 2.25 days compared with an average stay of 1.33 days for those patients exhibiting rapid cellular oxygenation recovery (p = 0.06). The slow recovery group had an average cross-clamp time of 40.1 ± 28.4 minutes, compared with 26.0 ± 8.5 minutes for the fast recovery group (p = 0.34). This study demonstrates for the first time that myocyte cellular oxygenation can be measured intraoperatively during cardiac surgery. Measurement of cellular oxygenation may be useful for improving myocardial preservation techniques.


Subject(s)
Cardiac Surgical Procedures/methods , Myocardium/pathology , Oxygen/chemistry , Thoracic Surgery/methods , Adolescent , Aorta/pathology , Child , Child, Preschool , Heart Arrest, Induced , Humans , Infant , Intensive Care Units , Length of Stay , Monitoring, Intraoperative/methods , Optics and Photonics/methods
7.
Appl Spectrosc ; 64(9): 973-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20828433

ABSTRACT

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 included Intralipid as a light scatterer. Spectra were also acquired from the rabbit forelimb. Three partial least squares (PLS) analyses were performed on second-derivative spectra, each separately calibrated to myoglobin oxygen saturation, hemoglobin oxygen saturation, or cytochrome aa3 oxidation. The three variables were measured from in vitro and in vivo spectra that contained all three chromophores. In the in vitro studies, measured values of myoglobin saturation, hemoglobin saturation, and cytochrome aa3 oxidation had standard errors of 5.9%, 7.4%, and 12.2%, respectively, with little cross-talk between the in vitro measurements. In the progression from normal oxygenation to ischemia in the rabbit forelimb, hemoglobin desaturated first, followed by myoglobin, while cytochrome aa3 reduction occurred last. The ability to simultaneously measure oxygenations in the vascular, intracellular, and mitochondrial compartments will be valuable in physiological studies of muscle metabolism and in clinical studies when oxygen supply or utilization are compromised.


Subject(s)
Electron Transport Complex IV/chemistry , Hemoglobins/chemistry , Myoglobin/chemistry , Oxygen/metabolism , Spectroscopy, Near-Infrared/methods , Animals , Capillaries/metabolism , Electron Transport Complex IV/metabolism , Forelimb/blood supply , Hemoglobins/metabolism , Ischemia/physiopathology , Least-Squares Analysis , Microscopy, Electron , Mitochondria/metabolism , Muscle, Skeletal/metabolism , Myoglobin/metabolism , Oxidation-Reduction , Rabbits
8.
Methods ; 46(4): 312-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18930151

ABSTRACT

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 and (dys)function in human muscle in vivo. Three innovations involving advances in optical spectroscopy (OS) and magnetic resonance spectroscopy (MRS) permit quantifying key compounds in energy metabolism to yield mitochondrial oxidation and phosphorylation fluxes. The first of these uses analytical methods applied to optical spectra to measure hemoglobin (Hb) and myoglobin (Mb) oxygenation states and relative contents ([Hb]/[Mb]) to determine mitochondrial respiration (O2 uptake) in vivo. The second uses MRS methods to quantify key high-energy compounds (creatine phosphate, PCr, and adenosine triphosphate, ATP) to determine mitochondrial phosphorylation (ATP flux) in vivo. The third involves a functional test that combines these spectroscopic approaches to determine mitochondrial energy coupling (ATP/O2), phosphorylation capacity (ATP(max)) and oxidative capacity (O2max) of muscle. These new developments in optical and MR tools allow us to determine the function and capacity of mitochondria noninvasively in order to identify specific defects in vivo that are associated with disease in human and animal muscle. The clinical implication of this unique diagnostic probe is the insight into the nature and extent of dysfunction in metabolic and degenerative disorders, as well as the ability to follow the impact of interventions designed to reverse these disorders.


Subject(s)
Energy Metabolism , Mitochondria/physiology , Animals , Hemoglobins/metabolism , Humans , Magnetic Resonance Spectroscopy/methods , Mitochondria, Muscle/physiology , Mitochondrial Diseases/physiopathology , Myoglobin/metabolism , Optics and Photonics , Oxidative Phosphorylation , Oxygen Consumption , Oxyhemoglobins/metabolism , Spectrum Analysis/methods
9.
Cell Metab ; 7(4): 312-20, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18396137

ABSTRACT

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 weeks. KO mice manifested encephalomyopathy including a retarded growth rate, lethargy, loss of motor skill, blindness, and elevated serum lactate. CI activity in submitochondrial particles from KO mice was undetectable by spectrophotometric assays. However, CI-driven oxygen consumption by intact tissue was about half that of controls. Native gel electrophoresis revealed reduced levels of intact CI. These data suggest that CI fails to assemble properly or is unstable without NDUFS4. KO muscle has normal morphology but low NADH dehydrogenase activity and subsarcolemmal aggregates of mitochondria. Nonetheless, total oxygen consumption and muscle ATP and phosphocreatine concentrations measured in vivo were within normal parameters.


Subject(s)
Electron Transport Complex I/deficiency , Electron Transport Complex I/metabolism , Mitochondria/enzymology , Mitochondrial Encephalomyopathies/metabolism , Adenosine Triphosphatases/metabolism , Animals , Cell Respiration , Electron Transport Complex I/genetics , Female , Liver/enzymology , Mice , Mice, Knockout , Mitochondrial Encephalomyopathies/genetics , Mitochondrial Encephalomyopathies/mortality , Muscle, Skeletal/cytology , Muscle, Skeletal/ultrastructure , NADH Dehydrogenase/deficiency , NADH Dehydrogenase/genetics , NADH Dehydrogenase/metabolism , Oxygen Consumption , Phenotype , Survival Analysis , Time Factors
11.
Appl Spectrosc ; 61(6): 665-9, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17650380

ABSTRACT

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 in optical spectra collected in vivo. However, the utility of this approach is limited without information on tissue concentrations of these species. Here we describe a strategy to quantify the contributions of Hb and Mb to in vivo optical spectra. We have found that the peak position of the deoxy-heme peak around 760 nm in the optical spectra of the deoxygenated tissue is a linear function of the relative contributions of Hb and Mb to the optical spectra. Therefore, analysis of this peak position, hereafter referred to as wavelength shift analysis, reveals the relative concentration of Hb to Mb in solutions and intact tissue. Biochemical analysis of muscle homogenates confirmed that the wavelength shift of the combined Hb/Mb peak in in vivo spectra reflects the ratio of concentrations (Hb/Mb) in muscle. The importance of quantifying the Hb contribution is illustrated by our data demonstrating that Hb accounts for approximately 80% of the optical signal in mouse skeletal muscle but only approximately 20% in human skeletal muscle. This advance will facilitate comparison of the metabolic properties between individual muscles and provides a fully noninvasive approach to measuring local respiration that can be adapted for clinical use.


Subject(s)
Algorithms , Hemoglobins/analysis , Muscle, Skeletal/metabolism , Myoglobin/analysis , Spectrum Analysis/methods , Adult , Animals , Female , Humans , Male , Mice , Middle Aged
12.
Shock ; 27(6): 695-700, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17505311

ABSTRACT

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 endotoxin (lipopolysaccharide [LPS]) than in controls. Four hours after intraperitoneal injection with LPS, adult guinea pigs were anesthetized, and hearts were excised and perfused in the Langendorff manner. Six control and eight LPS-exposed guinea pigs were studied. Myoglobin oxygen saturation was determined from analysis of optical reflectance spectra acquired from the left ventricular free wall. Myoglobin saturation was significantly higher at baseline with LPS than in controls (96.0% +/- 0.8% vs. 89.4% +/- 1.7%, P < 0.001). At the end of 30 s of ischemia, myoglobin saturation decreased to 15% +/- 1% in controls, but to only 60% +/- 7% in the LPS group. Myocardial performance was determined by measured left ventricular developed pressure, which was significantly depressed in the LPS-exposed hearts relative to controls (30 +/- 4 mmHg vs. 67 +/- 9 mmHg, P < 0.001). Myocardial oxygen consumption, calculated from measurements of arterial and venous PO2 and coronary flow, was lower in LPS hearts relative to controls (0.199 +/- 0.021 mL oxygen x min(-1) x g(-1) vs. 0.157 +/- 0.006 mL oxygen x min(-1) x g(-1)). In this model of sepsis in the perfused guinea pig heart, intracellular oxygenation was higher and oxygen consumption was lower than in controls. Cellular dysfunction seen in sepsis may be caused by compromised oxygen use rather than insufficient oxygen delivery. Optical spectroscopy has the potential to noninvasively monitor patients and their responses to therapy.


Subject(s)
Endotoxins/metabolism , Oxygen/metabolism , Sepsis/therapy , Spectrophotometry/methods , Animals , Equipment Design , Guinea Pigs , Heart , Hypoxia , Lipopolysaccharides/pharmacology , Male , Mitochondria/metabolism , Myocardium/metabolism , Myocardium/pathology , Myoglobin/metabolism , Perfusion , Phosphorylation , Sepsis/pathology
13.
Crit Care Med ; 34(8): 2217-23, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16763506

ABSTRACT

OBJECTIVE: 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. DESIGN: Prospective case series. SETTING: Pediatric intensive care unit of a tertiary children's hospital. PATIENTS: Six patients with diabetic ketoacidosis and altered mental status, requiring computed tomographic scan of the head. INTERVENTIONS: Study evaluations included: 1) transcranial Doppler evaluations to determine middle cerebral artery flow velocities and cerebral autoregulation, defined by the autoregulatory index, at 6 and 36 hrs; 2) continuous monitoring of regional cerebral oxygenation on the left lateral forehead using near-infrared spectroscopy for the first 24 hrs of admission; 3) serial measurement of S100B as a marker of central nervous system injury; and 4) follow-up head computed tomographic scan. RESULTS: Serial computed tomographic scans showed that four of six patients had changes in brain volume without overt cerebral edema. Initial scans showed narrowing of the third and lateral ventricles when compared with follow-up. There was no difference in middle cerebral artery flow velocities between admission and recovery at 36 hrs, despite Paco2 increasing during treatment. Cerebral flow was normal to increased, despite hypocapnia. Cerebral autoregulation was impaired in five of six patients at 6 hrs and normalized by 36 hrs. Mean regional cerebral oxygenation was measured in five of six patients and decreased linearly with time. Two patients showed maximal regional cerebral oxygenation before returning to baseline. There were no periods of low regional cerebral oxygenation in any patient at any time. No elevation in S100B was found. CONCLUSIONS: We found normal to increased cerebral blood flow, elevated regional cerebral oxygenation, impaired autoregulation, and changes in brain volume in clinically ill pediatric patients with diabetic ketoacidosis. We found no evidence of cerebral ischemia. These findings suggest that the pathophysiology of cerebral edema in diabetic ketoacidosis may involve a transient loss of cerebral autoregulation, allowing a paradoxic increase in cerebral blood flow and the development of vasogenic cerebral edema.


Subject(s)
Brain Edema/physiopathology , Brain/blood supply , Diabetic Ketoacidosis/physiopathology , Hemostasis/physiology , Hyperemia/physiopathology , Adolescent , Blood Flow Velocity/physiology , Brain/diagnostic imaging , Carbon Dioxide/blood , Child , Critical Illness , Hospitals, Pediatric , Humans , Infant , Intensive Care Units, Pediatric , Middle Cerebral Artery/diagnostic imaging , Nerve Growth Factors/blood , Oxygen/blood , Prospective Studies , S100 Calcium Binding Protein beta Subunit , S100 Proteins/blood , Spectroscopy, Near-Infrared , Tilt-Table Test , Ultrasonography, Doppler, Transcranial
14.
Pediatr Crit Care Med ; 7(2): 154-8, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16446597

ABSTRACT

OBJECTIVE: 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. DESIGN: Prospective observational study. SETTING: Tertiary children's hospital. PATIENTS: Eleven neonatal and pediatric patients requiring veno-arterial ECLS support between June 2000 and March 2003. INTERVENTIONS: Near infrared spectroscopy probe placement on left and right frontal regions of patients undergoing ECLS, before vessel cannulation or within 24 hrs of initiation of ECLS. MEASUREMENTS AND MAIN RESULTS: Regional cerebral oxygenation was measured every minute for 72 hrs or until the patient was decannulated. The effect of cannulation on rSO2i from each hemisphere of the brain and the relationship between ECLS flow and rSO2i during ECLS support and "trialing off" periods were determined. Ligation of the right carotid artery resulted in a 12-25% decrease in rSO2i from baseline in the right frontal region for a duration ranging from 17 to 45 mins before returning toward baseline. No substantial change in the left frontal region rSO2i was detected during cannulation. Following this depression in rSO2i on the right, there was a transient increase above baseline in rSO2i observed in both hemispheres on initiating ECLS. No correlation between ECLS flow and rSO2i was found over the 72-hr period. Periods of "trialing off" ECLS were not related to any change in rSO2i in either hemisphere. CONCLUSIONS: This study demonstrated no relationship between ECLS flow and rSO2i changes during the 72-hr observation period. A brief period of cerebral oxygen desaturation of the right frontal region at the time of right carotid ligation was seen in all three study patients examined during cannulation, followed by an increased rSO2i with initiation of ECLS flow. Near infrared spectroscopy measurement may offer an important adjunct for neurologic monitoring of ECLS patients.


Subject(s)
Brain/blood supply , Extracorporeal Membrane Oxygenation , Hemodynamics/physiology , Oxygen/blood , Carotid Artery, Common , Female , Frontal Lobe/blood supply , Humans , Infant , Infant, Newborn , Ligation , Male , Monitoring, Physiologic , Prospective Studies , Spectroscopy, Near-Infrared
15.
J Physiol ; 569(Pt 2): 467-73, 2005 Dec 01.
Article in English | MEDLINE | ID: mdl-16254011

ABSTRACT

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 understanding of the effects of ageing on coupling has been the lack of in vivo approaches to measure P/O. We use optical and magnetic resonance spectroscopy to independently quantify mitochondrial ATP synthesis and O2 uptake to determine in vivo P/O. Resting ATP demand (equal to ATP synthesis) was lower in the skeletal muscle of 30-month-old C57Bl/6 mice compared to 7-month-old controls (21.9 +/- 1.5 versus 13.6 +/- 1.7 nmol ATP (g tissue)(-1) s(-1), P = 0.01). In contrast, there was no difference in the resting rates of O2 uptake between the groups (5.4 +/- 0.6 versus 8.4 +/- 1.6 nmol O2 (g tissue)(-1) s(-1)). These results indicate a nearly 50% reduction in the mitochondrial P/O in the aged animals (2.05 +/- 0.07 versus 1.05 +/- 0.36, P = 0.02). The higher resting ADP (30.8 +/- 6.8 versus 58.0 +/- 9.5 micromol g(-1), P = 0.05) and decreased energy charge (ATP/ADP) (274 +/- 70 versus 84 +/- 16, P = 0.03) in the aged mice is consistent with an impairment of oxidative ATP synthesis. Despite the reduced P/O, uncoupling protein 3 protein levels were not different in the muscles of the two groups. These results demonstrate reduced mitochondrial coupling in aged skeletal muscle that alters cellular metabolism and energetics.


Subject(s)
Aging/physiology , Energy Metabolism , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Oxidative Phosphorylation Coupling Factors/physiology , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Carrier Proteins/metabolism , Female , Ion Channels , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred C57BL , Mitochondrial Proteins , Muscle, Skeletal/chemistry , Muscle, Skeletal/cytology , Oxygen Consumption , Time Factors , Uncoupling Protein 3
16.
Am J Physiol Heart Circ Physiol ; 288(5): H2062-7, 2005 May.
Article in English | MEDLINE | ID: mdl-15591100

ABSTRACT

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 cardiac contractility was increased with epinephrine and decreased during cardiac arrest with KCl. Infusion of epinephrine to achieve a doubling of contractility, as measured by left ventricular maximum pressure change over time (dP/dt), resulted in a decrease in mean myoglobin saturation from 79% at baseline to 65% and a decrease in coronary venous oxygen tension from 155 mmHg at baseline to 85 mmHg. Cardiac arrest with KCl increased mean myoglobin saturation to 100% and coronary venous oxygen tension to 390 mmHg. A previously developed computer model of oxygen transport in the myocardium was used to calculate the probability distribution of intracellular oxygen tension and the hypoxic fraction of the myocardium with an oxygen tension below 0.5 mmHg. The hypoxic fraction of the myocardium was approximately 15% at baseline, increased to approximately 30% during epinephrine infusion, and fell to approximately 0% during cardiac arrest. The coronary venous adenosine concentration changed in parallel with the hypoxic fraction of the myocardium during epinephrine and KCl. It is concluded that catecholamine stimulation of buffer-perfused hearts increases hypoxia in the myocardium and that the increase in venous adenosine concentration is a reflection of the larger hypoxic fraction of myocardium that is releasing adenosine.


Subject(s)
Adenosine/metabolism , Myocardial Contraction/physiology , Myocardium/metabolism , Oxygen/metabolism , Animals , Buffers , Epinephrine/pharmacology , Guinea Pigs , Hypoxia/metabolism , Hypoxia/physiopathology , In Vitro Techniques , Male , Myocardial Contraction/drug effects , Oxygen Consumption/physiology , Potassium Chloride/pharmacology , Sympathomimetics/pharmacology
17.
Am J Physiol Cell Physiol ; 286(2): C457-63, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14522819

ABSTRACT

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 normal mitochondria. To measure mitochondrial coupling under physiological conditions, we have developed a procedure for determining the P/O of skeletal muscle in vivo. This technique measures ATPase and oxygen consumption rates during ischemia with 31P magnetic resonance and optical spectroscopy, respectively. This novel approach allows the independent quantitative measurement of ATPase and oxygen flux rates in intact tissue. The quantitative measurement of oxygen consumption is made possible by our ability to independently measure the saturations of hemoglobin (Hb) and myoglobin (Mb) from optical spectra. Our results indicate that the P/O in skeletal muscle of the mouse hindlimb measured in vivo is 2.16 +/- 0.24. The theoretical P/O for resting muscle is 2.33. Systemic treatment with 2,4-dinitrophenol to partially uncouple mitochondria does not affect the ATPase rate in the mouse hindlimb but nearly doubles the rate of oxygen consumption, reducing in vivo P/O to 1.37 +/- 0.22. These results indicate that only a small fraction of the oxygen consumption in resting mouse skeletal muscle is nonphosphorylating under physiological conditions, suggesting that mitochondria are more tightly coupled than previously thought.


Subject(s)
Ischemia/metabolism , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , 2,4-Dinitrophenol/pharmacology , Adenosine Triphosphate/biosynthesis , Animals , Female , Hemoglobins/metabolism , Hindlimb , Magnetic Resonance Spectroscopy , Mice , Muscle, Skeletal/blood supply , Myoglobin/metabolism , Oxidation-Reduction , Oxygen Consumption , Phosphorus , Spectrum Analysis , Uncoupling Agents/pharmacology
18.
Am J Physiol Heart Circ Physiol ; 285(5): H1819-25, 2003 Nov.
Article in English | MEDLINE | ID: mdl-12869374

ABSTRACT

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 intracellular myoglobin saturation previously reported from traditional buffer-perfused hearts. Studies were performed at 37 degrees C with hearts paced at 240 beats/min and a constant perfusion pressure of 80 cmH2O. It was found that during perfusion with a hematocrit of 5%, baseline mean myoglobin saturation was 93% compared with 72% during buffer perfusion. Mean myoglobin saturation, ventricular function, and oxygen consumption remained fairly constant for arterial perfusate oxygen tensions above 100 mmHg and then decreased precipitously below 100 mmHg. In contrast, mean myoglobin saturation, ventricular function, and oxygen consumption began to decrease even at high oxygen tension with buffer perfusion. The present results demonstrate that perfusion with 5% red blood cells in the perfusate increases the baseline mean myoglobin saturation and better preserves cardiac function at low oxygen tension relative to buffer perfusion. These results suggest that caution should be used in extrapolating intracellular oxygen dynamics from buffer-perfused to blood-perfused hearts.


Subject(s)
Erythrocytes , Hypoxia/metabolism , Myocardium/metabolism , Oxygen Consumption/physiology , Animals , Arteries , Buffers , Coronary Circulation , Female , Guinea Pigs , In Vitro Techniques , Male , Myoglobin/metabolism , Perfusion , Spectrum Analysis , Veins
19.
Am J Physiol Heart Circ Physiol ; 285(5): H1826-36, 2003 Nov.
Article in English | MEDLINE | ID: mdl-12869375

ABSTRACT

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, interstitial, and parenchymal spaces) is simulated. The model is used to interpret experimental data on mean cardiac tissue myoglobin saturation and to reveal differences in tissue oxygenation between buffer-perfused and red blood cell-perfused isolated hearts. Interpretation of measured mean myoglobin saturation is strongly dependent on the oxygen content of the perfusate (e.g., red blood cell-containing vs. cell-free perfusate). Model calculations match experimental values of mean tissue myoglobin saturation, measured mean myoglobin, and venous oxygen tension and can be used to predict distributions of intracellular oxygen tension. Calculations reveal that approximately 20% of the tissue is hypoxic with an oxygen tension of <0.5 mmHg when the buffer is equilibrated with 95% oxygen to give an arterial oxygen tension of over 600 mmHg. The addition of red blood cells to give a hematocrit of only 5% prevents tissue hypoxia. It is incorrect to assume that the usual buffer-perfused Langendorff heart preparation is adequately oxygenated for flows in the range of < or =10 ml. min-1. ml tissue-1.


Subject(s)
Coronary Circulation/physiology , Models, Cardiovascular , Myocardium/metabolism , Oxygen/metabolism , Animals , Buffers , Humans , In Vitro Techniques , Microcirculation/physiology , Myoglobin/metabolism , Perfusion , Predictive Value of Tests
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