Tissue Oxygen Metabolism Research Articles

Effect Over Time of Endotoxin Adsorption Therapy in Sepsis

Despite the use of potent antibiotics and intensive supportive care, the mortality among patients with sepsis and Gram-negative bacteremia remains high. In recent years, endotoxin adsorption therapy (PMX-DHP, polymyxin-direct hemoperfusion) has been widely used in Japan to remove endotoxin, a causative agent of sepsis. In septic patients whose clinical condition may change at any moment, the decision of when to perform blood purification in addition to conventional intensive care is a critical factor in the therapeutic strategy and prognosis. In the present study, we investigated the effect over time of PMX-DHP in sepsis. The subjects were 16 patients with systemic inflammatory response syndrome (SIRS) who required surgical treatment including a surgical operation and drainage. The following six parameters were compared between the first and second PMX-DHP: mean blood pressure and time-restricted urine at four time points - at baseline and at 6, 24 and 72 h after PMX-DHP; and white blood cell count, platelet count, base excess and Septic Severity Score (SSS) at 24 and 72 h after PMX-DHP. Mean blood pressure improved over time up to 24 h after both the first and second PMX-DHP. Time-restricted urine volume improved only at 6 h after the first PMX-DHP. White blood cell count improved over time up to 24 h after both the first and second PMX-DHP. The SSS improved at all time points studied except for 3 days after the second PMX-DHP. We conclude that PMX-DHP is expected to have important implications in terms of (i) correction of clinical conditions (by severity assessment); (ii) improvement of hemodynamics; (iii) possible anti-inflammatory effect; and (iv) possible improvement of oxygen metabolism in tissues.

Efficacy of Continuous Hemodiafiltration for Patients with Congestive Heart Failure

Background/Aims: The basic principle of treatment of congestive heart failure is achieving adequate control of preload and afterload through enhancement of cardiac contractility. In severe cases, however, we have usually applied continuous hemodiafiltration (CHDF) as a type of mechanical support. In this study, we investigated hemodynamic changes caused by CHDF in patients with congestive heart failure. Methods: We treated seven patients with congestive heart failure complicated by multiple organ failure by CHDF over 72 h, during which we measured hemodynamic parameters to determine their changes. Results: Implementation of CHDF resulted in a significant decrease in pulmonary artery occluded pressure and significant increases in cardiac index and left ventricular stroke work index. In addition, 72-hour cumulative water balance was found to be –1,791 ± 2,119 ml, and systemic vascular resistance index decreased significantly. Conclusion: Hemodynamics of patients were improved with CHDF through strict control of preload and consequently tissue oxygen metabolism was improved.

Effect of graded hypoxia on the rat hepatic tissue oxygenation and energy metabolism monitored by near-infrared and 31P nuclear magnetic resonance spectroscopy.

Alteration in hepatic cellular adenosine triphosphate (ATP) levels has been shown to be a sensitive index for hypoxic damage. Hepatic ATP metabolism can be monitored by 31P nuclear magnetic resonance (NMR). Near-infrared spectroscopy (NIRS) can measure tissue oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and cytochrome oxidase (Cyt Ox), which reflect ATP production. In this study, hepatic oxygenation parameters have been correlated with ATP metabolism under graded hypoxia. Sprague-Dawley rats underwent laparotomy for liver exposure. NIRS probes and an NMR coil were placed on the liver and the animal was positioned in the NMR magnet. Graded hypoxia was achieved by a stepwise reduction of the fraction of inspired oxygen (FiO2) from 15 to 4%. Recovery between the hypoxic periods was achieved using 30% oxygen. Hepatic tissue oxygenation parameters were measured continuously by NIRS; 31P-NMR spectra obtained at 1 min intervals from energy metabolites and intracellular pH were calculated. All the hypoxic grades produced an immediate reduction in HbO2 with a simultaneous increase in Hb. Cyt Ox was reduced significantly only with FiO2 of </= 10%. 31P-NMR spectra showed a significant decrease in cellular beta nucleoside triphosphate (beta-NTP) only with FiO2 of </= 10%. Significant correlation was seen between beta-NTP and HbO2 (r=0.85), Hb (r=-0.74), and Cyt Ox (r=0.81). Cyt Ox was reduced with intracellular hypoxia and correlated temporally with the reduction of cellular beta-NTP, and therefore could be used as an index for the changes in beta-NTP with hypoxia.

Nondestructive and real-time evaluation of liver viability in brain dead donor for liver transplantation using near-infrared spectroscopy.

A reliable and less-invasive method is currently desired to assess the hemodynamic and functional alteration associated with brain death in the organs of donor candidates. Near-infrared spectroscopy (NIRs) was applied to rat liver in brain-dead donors for assessing tissue oxygenation and intracellular energy metabolism as a means of monitoring the liver viability in the brain-dead donor. Brain-dead rats were divided into 4 according to doses of epinephrine and vasopressin administered. Arterial ketone bodies ratio (AKBR), hyaluronic acid (HA), and NIRs monitoring of a liver graft were performed in the brain-dead phase before the grafts were transplanted into syngeneic rats. NIRs monitoring of oxygenated hemoglobin (Hb) and cytochrome aa3 oxidase (Cytaa3) redox state reflected changes in the hepatic microcirculation and intracellular oxygenation. The administration of high-dose epinephrine proved to be contraindicated due to catecholamine-induced hypoxic stress, while combined administration of adrenaline and vasopressin at an optimal dose rate was beneficial for preservation of the liver viability. The data obtained by NIRs were significantly correlated with the 7-day survival of recipients after liver transplantation. Thus, we conclude that NIRs is a sensitive and nondestructive method for monitoring alterations in the viability of brain-dead liver and can predict liver graft outcome.

Ischemia/Reperfusion Injury of the Pancreas: A New Animal Model

Background.Ischemia/reperfusion is thought to play an important role in the development of postimplantation pancreatitis after pancreas transplantation and also in the transition of edematous pancreatitis into necrotizing pancreatitis. Previous studies have suggested that impairment of microcirculation and hence tissue oxygenation and energy metabolism may be critical steps in this process.Materials and methods.In landrace pigs vascular isolation of the pancreatic tail was performed. Morphological alterations, tissue oxygenation, and energy metabolism were assessed in response to 3 h of global warm ischemia and the following reperfusion.Results.A rapid onset of morphological alterations immediately after reperfusion was noted. Oxygen consumption and ATP levels were markedly decreased, and tissue oxygenation was severely impaired especially during the first hour after reperfusion. ATP tissue levels and oxygen consumption 10 min after reperfusion correlated significantly with the morphological changes at the end of the experiment.Conclusion.These findings can be explained by a failure of nutritive capillary perfusion and concomitant shunt perfusion. Therefore an impaired microcirculation rather than an impaired oxygen utilization shortly after reperfusion is of major relevance in the development of the ischemia/reperfusion injury of the pancreas.

The effects of desflurane on splanchnic hemodynamics and oxygenation in the anesthetized pig.

This study was designed to investigate the effects of desflurane on systemic and splanchnic hemodynamics, O2 delivery and O2 uptake, tissue oxygenation (as monitored by surface PO2 electrodes), and hepatic oxygen-dependent intermediary metabolism (hepatic lactate uptake, intestinal lactate production, ketone-body ratio) in the pig. We studied 11 anesthetized (i.e., ketamine, flunitrazepam, vecuronium) and ventilated domestic pigs (17-23 kg). After instrumentation, desflurane was administered randomly at 0.5 minimum alveolar anesthetic concentration (MAC) (4.2 vol %) and 1.0 MAC (8.3 vol %). Desflurane caused dose-dependent decreases in heart rate, mean arterial blood pressure, and cardiac output. Hepatic arterial blood flow was not affected at 0.5 MAC but decreased at 1.0 MAC. In contrast, portal and superior mesenteric arterial blood flow decreased at 0.5 MAC but did not show any further significant decrease at 1.0 MAC. Total hepatic blood flow decreased dose-dependently. Although O2 deliveries of whole body, liver, and small intestine were markedly reduced at both concentrations, respective O2 uptakes did not change significantly. The decreases in O2 deliveries were reflected by moderate disturbances in hepatic and small intestinal surface PO2. No evidence for severe tissue hypoxia could be detected. Desflurane had no adverse effects on hepatic and small intestinal metabolic function. These data indicate that hepatic and small intestinal O2 reserve capacity is impaired by desflurane.

TONOMETRY: A Review of Clinical Studies

In the quest for a better monitor of end-organ injury in the critically ill patient, gastrointestinal tonometry to measure intramucosal pH (pHi) and PCO2 has been advocated by several investigators. The authors discuss the principles and practice of gastric tonometry. In addition, the clinical applications of the technique are discussed with close attention to the use of pHi as an indicator of mucosal ischemia, ICU morbidity rates, and ICU mortality rates in surgical and medical patient populations. Although prognostic capability is an important role for tonometry, the principal benefit of the technology is its efficacy as an index of tissue resuscitation and as a guide to medical intervention. Given recent technical advances, gastrointestinal tonometry may gain increasing use in the assessment of tissue perfusion and oxygen metabolism.

THE CARDIOPULMONARY, EICOSANOID, AND TISSUE MICROANATOMIC EFFECTS OF FLUCONAZOLE DURING GRADED BACTEREMIA

Imidazole compounds have been shown to be beneficial in systemic sepsis and inflammation. The purpose of this study was to delineate the effects of fluconazole on systemic hemodynamics and on microanatomy of the heart, lung, liver, and kidney parenchyma of swine during graded bacteremia. Eighteen adult swine were studied in three groups: 1), anesthesia control; 2), septic control (Aeromonas hydrophila, 10(9)/mL, infused i.v. for 4 h); 3) fluconazole (fluconazole, 30 mg/kg i.v., followed by A. hydrophila infusion). After 4 h of graded bacteremia, autopsy was performed. Compared with the septic control group, cardiac index, oxygen delivery, and oxygen consumption were reduced significantly after fluconazole pretreatment, and mixed venous hemoglobin oxygen saturation (SVO2) and oxygen extraction were increased. Plasma thromboxane A2 and leukotriene levels were not affected by fluconazole. Computerized digital image analysis of the liver, heart, and kidney specimens revealed no statistically significant differences between the septic control group and fluconazole-pretreated animals. In the lung specimens, preinfusion of fluconazole decreased alveolar wall thickness in septic swine (anesthesia control group: 8.15 x 10(-3) +/- 1.3 x 10(-3)mm versus septic control group: 9.9 x 10(-3) +/- 1.3 x 10(-4) versus fluconazole group: 6.8 x 10(-3) +/- 1.6 x 10(-3); p < or = .05). Fluconazole pretreatment before graded bacteremia has no beneficial effect on cardiopulmonary performance or septic tissue edema of the heart, kidney, or liver. Tissue oxygen metabolism might be down-regulated by fluconazole. However, preinfusion of fluconazole appears to normalize the sepsis-induced increase in pulmonary alveolar wall thickness. The net significance of these changes on clinical outcome is not clear from these data.

A.361 Influence of inhaled nitric oxide on tissue oxygen metabolism

A.361 Influence of inhaled nitric oxide on tissue oxygen metabolism

A Combination of Flurbiprofen Axetil and Dobutamine Improved Tissue Oxygen Metabolism in a Patient with Sepsis due to Ascending Cholangitis

A case of ascending cholangitis with sepsis where a combination of flurbiprofen axetil and dobutamine improved tissue oxygen metabolism is reported. A 23-year-old man was admitted to our hospital with a diagnosis of ascending cholangitis. He had a history of hepatic porto-enterostomy for biliary atresia at 90 days after birth. The patient fell into respiratory failure with sepsis one day after admission and was transfered to our ICU. Mechanical ventilation via tracheal tube was performed. Hemodynamic values including an elevated heart rate (128min-1) and cardiac index (7.8l·min-1·m-2) indicated a hyperdynamic state, but oxygen uptake decreased with a lowered oxygen extraction ratio (13%) and elevated mixed venous oxygen saturation (89.3%). Severe lactic acidosis (lactate 9.8mg·dl-1) occurred, indicating that oxygen debt induced hypoxic tissue injury. Flurbiprofen axetil (2mg·hr-1) was administered to inhibit systemic inflammatory response and decrease cellular oxygen demand. As body temperature decreased from 38.2°C to 37.4°C, systolic arterial pressure, cardiac index and oxygen delivery index declined from 130mmHg, 7.8l· min-1·m-2, and 1, 226ml·min-1·m-2 to 80mmHg, 5.7l·min-1·m-2, and 744ml·min-1·m-2, respectively. Body temperature, systolic arterial pressure, cardiac index and oxygen delivery index reached adequate levels of 37.4°C, 100mmHg, 6.1l·min-1·m-2, and 7, 180ml·min-1·m-2, respectively after combined administration of flurbiprofen axetil at a reduced dose of 1.5mg·hr-1, and dobutamine at a dose of 2μg·kg-1·min-1. Mixed venous oxygen saturation decreased to 85.4% and the oxygen extraction ratio increased to 18%. Lactate was reduced to 2.3mg·dl-1.These findings demonstrated improvement of tissue oxygen metabolism. It may be useful to keep a supranormal level of oxygen delivery and to reduce cellular oxygen demand adequately by nonsteroidal anti-inflammatory drugs for the treatment of severe sepsis with oxygen debt.

Sequential studies of severely hypometabolic tissue volumes after permanent middle cerebral artery occlusion. A positron emission tomographic investigation in anesthetized baboons.

In the positron emission tomography literature, markedly hypometabolic brain tissue (oxygen metabolism < 1.3 to 1.7 mL.100 g-1.min-1) has often been equated with irreversible damage in the human brain. By serial positron emission tomography measurements, we investigated the temporal evolution of the volume of severely hypometabolic brain tissue after permanent middle cerebral artery occlusion in anesthetized baboons with, as a perspective, the development of rational therapeutic strategies. Seven anesthetized and ventilated baboons underwent sequential positron emission tomography examinations with the 15O steady-state technique before and 1, 4, 7, and 24 hours and 14 to 29 days after occlusion. In each baboon the infarct volume was calculated by quantitative histological procedures after 19 to 41 days of occlusion. The sequential measurement of regional oxygen metabolism demonstrated an extension (for > or = 24 hours) of the volume of severely hypometabolic tissue as defined by both absolute and relative metabolic thresholds, and this profile of evolutivity is observed no matter the threshold used. Mean (+/- SEM) infarction volume of 2.4 +/- 0.6 cm3 was comparable to a tissue volume with oxygen consumption < 40% of contralateral metabolism. The volume of hypometabolic tissue was essentially stable at the 1-, 4-, and 7-hour postocclusion studies, increased markedly at the 24-hour study point, and increased even further in the chronic-stage study (on average, 17 days after occlusion). The tissue that eventually displayed a severely hypometabolic state at the final measurement showed a significant decrease of oxygen metabolism and cerebral blood flow at each time analyzed. In that tissue, the oxygen extraction fraction increased significantly at 1 hour (although not thereafter). The extension of severely hypometabolic volume after middle cerebral artery occlusion reinforces the concept of a dynamic penumbra and suggests the existence of a relatively large window of therapeutic opportunity in which it may be possible to develop neuroprotective strategies. Our study suggests that maximum infarct volume is determined at some time between 24 hours and 17 days after permanent middle cerebral artery occlusion in anesthetized baboons.

Tissue oxygenation in low flow states and during hypoxemia

Tissue oxygenation during ischemia and hypoxia is critical to cellular viability. Adequate tissue oxygenation reflects a balance between oxygen delivery (DO2) and oxygen demand. At critical levels of DO2, oxygen consumption (VO2) declines due to supply dependency, indicating inadequate tissue oxygenation and impaired cellular metabolism. The mechanism by which DO2 is compromised (hypoxia vs. ischemia) determines the level of delivery at which VO2 becomes supply dependent. Tonometry is a method used to assess the adequacy of gut oxygenation. Studies using tonometric monitoring of intramural pH have shown that tonometry detects early tissue anaerobiosis and net adenosine triphosphate (ATP) hydrolysis. A decrease in intramural pH strongly correlates with the onset of supply dependency in tissue VO2. Inadequate intestinal oxygenation determined by tonometry has predicted clinical outcomes and complications in patients at risk. Gut tonometry may provide an early indication of inadequate tissue oxygenation. This early recognition is necessary to mitigate adverse consequences, including ATP catabolism, the production of reactive oxygen metabolites, and the activation of the inflammatory process, which can lead to progressive cellular dysfunction and cell death.

Optical mapping of inner retinal tissue PO2.

A high resolution optical mapping procedure was developed to visualize oxygen concentration levels topographically within the tissue of the inner retina in vivo. The novel optical mapping procedure has the potential for describing oxygen metabolism in retinal and other body tissues and elucidating the coupling of metabolism to function. The method is based upon the fluorescence quenching by molecular oxygen of a lipid soluble probe substance which accumulates within the lipid bilayers of tissue cells. The optical mapping system can provide more than 300,000 values of tissue PO2 in space with millisecond time resolution. Optical maps of inner retinal tissue PO2 were imaged under conditions of normoxia, hyperoxia, and for a retina which received restricted panretinal photocoagulation. Moreover, the effects of transient increases in intraocular pressure were also investigated. An O2 consumption rate of 5.48 +/- 0.50 (SEM) x 10(-3) ml O2/ml tissue/min for the light-adapted rat inner retina was estimated from the application of a Krogh cylinder diffusion model to tissue PO2 gradients measured in the capillary-free zone around arterioles. Similarly, arterioles oxygenated a surrounding cylinder of tissue with a mean radius of 144.73 +/- 5.52 (SEM) microns. Histograms of PO2 values within inner retinal tissue (mean PO2 = 25.03 mm Hg, median = 24.58 mm Hg) showed remarkable correspondence to those determined invasively in brain by others, using O2 microcathodes, possibly suggesting a similarity in the underlying capillary architectures of the two neural tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluid Resuscitation and Tissue Oxygen Metabolism in Critically Ill Patients

Fluid Resuscitation and Tissue Oxygen Metabolism in Critically Ill Patients

Nuclear magnetic resonance spectroscopy and the study of tissue oxygen metabolism: a review.

Nuclear magnetic resonance (NMR) techniques are being increasingly utilised as an in vivo method to monitor tissue oxygen concentration in various organs. In muscle and heart, proton NMR spectroscopy of myoglobin has been used to calculate local oxygen tension through the oxygen sensitivity of the histidine group signal intensity. Similarly, spin lattice relaxation times of perfluorocarbon emulsions are oxygen sensitive, and this property has been taken advantage of to produce oxygen maps of brain by fluorine NMR imaging. Phosphorus NMR spectroscopy has also been extensively used to monitor bioenergetic state, which under some conditions, is directly related to tissue oxygen tension. This review will focus on these NMR techniques for oxygen determination, and will critically assess their utility for further studies.

光を体内に通して生体の機能をはかる : 光CTの開発

光を体内に通して生体の機能をはかる : 光CTの開発

Hemodynamic Change and Tissue Oxygen Metabolism in Sepsis due to Peritonitis

Hemodynamic Change and Tissue Oxygen Metabolism in Sepsis due to Peritonitis

Cardiorespiratory Effects of Pressure Controlled Inverse Ratio Ventilation in Severe Respiratory Failure

Cardiorespiratory values were measured in nine patients with severe respiratory failure before and following initiation of pressure controlled inverse ratio ventilation (PC-IRV) at an inspiratory to expiratory ratio of 2:1. All patients showed increases in PaO2, with the mean PaO2 rising from 63 +/- 4 (mean +/- SEM) to 76 +/- 8 mm Hg. Peak inspiratory pressure fell from 44 +/- 4 to 39 +/- 2 cm H2O. There were no significant changes in any hemodynamic or oxygen metabolism variable associated with the institution of PC-IRV. In particular, no significant alteration in cardiac index, pulmonary artery pressures, oxygen delivery, oxygen consumption, or oxygen extraction ratio occurred with the use of PC-IRV. These results suggest that PC-IRV may be a useful ventilatory modality in the treatment of severe respiratory failure since it results in improvement in arterial oxygenation without any deterioration in hemodynamic or tissue oxygen metabolism parameters.

In vivo study of tissue oxygen metabolism using optical and nuclear magnetic resonance spectroscopies.

In vivo study of tissue oxygen metabolism using optical and nuclear magnetic resonance spectroscopies.

Blood flow, tissue oxygenation, pH distribution, and energy metabolism of murine mammary adenocarcinomas during growth.

Many solid tumors are relatively resistant to non-surgical therapeutic assaults. A variety of factors are involved in the lack of responsiveness of these neoplasms including cellular heterogeneity due to genetic differences between cells, and physiological factors created by inadequate and heterogeneous vascular networks. Thus, properties such as tumor blood flow, tissue oxygenation, pH distribution and energy metabolism, factors which generally go hand in hand, markedly influence the therapeutic response. Since the strategic approach must consider the physiological microenviron-ment of the cells within a tumor mass and -if possible- should exploit the metabolic micromilieu in designing therapies, we have measured relevant parameters in a well established murine tumor cell line with a known size dependent increase in the radiobiologicaly hypoxic cell fraction.