Marker Of Anaerobic Metabolism Research Articles

Cancer Microenvironment Defines Tumor-Infiltrating Lymphocyte Density and Tertiary Lymphoid Structure Formation in Laryngeal Cancer

BackgroundThe presence and activity of tumor-infiltrating lymphocytes (TILs) is a key parameter related to the antitumor immune response. A large number of studies reveal TIL density as a prognostic marker and predictor of response to radiotherapy, chemotherapy, and immunotherapy.MethodsWe examined the TIL and tertiary lymphoid structure TLS density in the invading front and inner tumor stroma, in a 33 squamous cell laryngeal carcinomas (LSCC) treated with laryngectomy. TIL and TLS densities were in parallel examined with markers of anaerobic metabolism, vascular density (VD), vascular survival ability (VSA), and histopathological parameters.ResultsTIL and TLS densities significantly decreased in inner tumor areas (p < 0.0001). TIL density in the invading tumor front was inversely related with lymph node involvement (p = 0.03), HIF1α expression (p = 0.008), vessel density (p = 0.02), and MIB1 (p = 0.006). TIL density in inner stroma was inversely linked to local invasion (marginal p = 0.05), tumor budding (TB) (p = 0.005), MIB1 (p = 0.02), and HIF1α expression (p = 0.02). Low-TLS density in the invading front and in inner tumor areas was related to high TB (p = 0.02 and 0.002, respectively), HIF1α (p = 0.003 and 0.01, respectively), and LDH5 expression (p = 0.003 and 0.007, respectively). CD4+, FOXP3+ TIL density, and FOXP3+/CD8+ ratio were directly associated with VSA (p = 0.008, 0.02, and 0.05, respectively).ConclusionPoor immune response is related to hypoxic background and anaerobic metabolism, as well as increased invasive and metastatic ability. Regulatory TIL markers are linked with increased angiogenic potential. The prognostic, predictive, and therapy-guiding value of TILs in clinical practice demands thorough investigation.

Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans.

Elevated circulating lactate has been associated with obesity and insulin resistance. The aim of the current study was to determine if lactate-induced lysine lactylation (kla), a post-translational modification, was present in human skeletal muscle and related to insulin resistance. Fifteen lean (Body Mass Index: 22.1 ± 0.5 kg/m2) and fourteen obese (40.6 ± 1.4 kg/m2) adults underwent a muscle biopsy and 2-h oral glucose tolerance test. Skeletal muscle lactylation was increased in obese compared to lean females (19%, p < 0.05) and associated with insulin resistance (r = 0.37, p < 0.05) in the whole group. Skeletal muscle lactylation levels were significantly associated with markers of anaerobic metabolism (plasma lactate and skeletal muscle lactate dehydrogenase [LDH], p < 0.05) and negatively associated with markers of oxidative metabolism (skeletal muscle cytochrome c oxidase subunit 4 and Complex I [pyruvate] OXPHOS capacity, p < 0.05). Treatment of primary human skeletal muscle cells (HSkMC) with sodium lactate for 24 h increased protein lactylation and IRS-1 serine 636 phosphorylation in a similar dose-dependent manner (p < 0.05). Inhibition of glycolysis (with 2-deoxy-d-glucose) or LDH-A (with sodium oxamate or LDH-A siRNA) for 24 h reduced HSkMC lactylation which paralleled reductions in culture media lactate accumulation. This study identified the existence of a lactate-derived post-translational modification in human skeletal muscle and suggests skeletal muscle lactylation could provide additional insight into the regulation of skeletal muscle metabolism, including insulin resistance.

Intramucosal pH as a criterion for the organism emergency from hepatospanchnic ischemia, or centralization of blood flow

In critical conditions, despite the restoration of systemic hemodynamics and overall oxygen delivery, tissue hypoxia and reduced oxygen extraction remain. One of the important tasks of intensive care for critical conditions is the early diagnosis of tissue perfusion disorders. In clinical circumstances, signs of hypoperfusion are arterial hypotension, tachycardia, oliguria, encephalopathy, low body temperature, the disappearance of skin capillary pattern, metabolic lactate acidosis. However, blood pressure is an insensitive indicator of tissue hypoperfusion itself. Experimental clinical trials have repeatedly documented that local perfusion pressure in critical conditions does not directly depend on systemic blood pressure. Lactate is not a specific marker of anaerobic metabolism, but rather impaired microcirculation seems to be one of the possible mechanisms of hyperlactatemia. Reliable markers of tissue perfusion and the effectiveness of early targeted therapy are regional capnometry (gastric intramucosal pH, sublingual pCO2), a saturation of mixed venous blood, etc. Intramucosal pH is of particular practical importance as a marker of regional capnometry. The aim of the study is the analysis of literature sources devoted to the effectiveness and diagnostic significance of intramucosal pH as a marker of regional perfusion. The value of intramucosal pH was evaluated: 1) during abdominal operations and the development of postoperative complications in comparison against IL-6 and IL-8; 2) during and after surgical interventions in conditions of prolonged cardiopulmonary bypass to assess the adequacy of blood supply to the abdominal organs; 3) in experimental septic shock compared to the values of lactate and hypoxanthine concentration in the liver and arterial blood; 4) the correlation between intramucosal pH va-lues, indices of the pediatric mortality risk scale, forming of great (cardiac arrest, shock) and minor (hypotension, hypovolemia, arrhythmia) hemodynamic complications and duration of staying in intensive care unit and intensive therapy; 5) during laparoscopic cholecystectomy in apparently healthy patients with the simultaneous calculation of the difference between arterial and intramucosal pH. Intramuscular pH-controlled intensive therapy is a separate fragment: an intramucosal pH of less than 7.3 reflects splanchnic hypoperfusion and is an indicator of the unfavorable outcomes; intramucousal pH of more than 7.3 is a criterion for the emergency of the organism from hepatosplanchic ischemia, i.e. centralization of blood circulation. Therefore, the intramucosal pH is valuable in the clinical picture of critical conditions as a marker of regional perfusion measured by capnometry, which allows monitoring that reflects the perfusion of the intestinal wall. The lower threshold is 7.35 (the sensitivity of the method is 67 %, specificity is 74 %). An intramucosal pH of &lt; 7.3 reflects splanchnic hypoperfusion and is an indicator of an adverse outcome. An alternative measurement of intramucosal pCO2, pCO2 in arterial blood and the difference [P (1-a) CO2] is a more reliable index of intestinal oxygenation than single intramucosal pH, but rather pH (1-a) makes it possible to adequately assess the acid-base state of arterial blood. The improvement and widespread use of capnometry and capnography for monitoring during general anaesthesia and intensive care, on the one hand, and modern knowledge of the pathophysiology of gas exchange, on the other hand, stimulate the wider use of less invasive and more affordable methods of regional capnometry and aerial tonometry.

Effect of reproduction cycle stage on energy metabolism responses in a sentinel species (Dreissena polymorpha) exposed to cadmium: What consequences for biomonitoring?

Metal trace elements such as cadmium (Cd) are commonly present in ecosystems and could lead to impairment of mitochondrial functions and energy imbalance in aquatic organisms including molluscs. Combined exposure to increasing temperatures and Cd could enhance such an impact on animals. Seasonal fluctuations, such as temperature, and the corresponding reproduction cycle can affect biomarker responses. However, the reproduction cycle stage is rarely taken into account in ecotoxicological studies. Thus, this work aimed at understanding energy metabolism responses in a sentinel species, Dreissena polymorpha. Mussels were collected during the rest and the reproduction periods and were exposed to 10 μg.L−1 of cadmium (Cd) at two temperatures (in situ temperature and in situ temperature + 5°C) during 7 days. Energy metabolism was monitored by measuring reserves and energy nucleotides charge and by assessing aerobic and anaerobic metabolism markers, and upstream regulation pathways. Markers related to OXPHOS activity revealed seasonal variations under laboratory conditions. Conversely, adenylate nucleotides, glycogen, lipid and transcript levels of AMP-activated protein kinase, citrate synthase, ATP synthase and cytochrome b encoding genes remained steady after the acclimation period. No evident effect of Cd on energy metabolism markers was noticed for both exposures although the transcript level of succinate dehydrogenase and citrate synthase encoding genes decreased with Cd during the rest period. Cellular stress, revealed by lipid peroxidation and catalase mRNA levels, only occurred in Cd and warming co-exposed mussels during the reproduction period. These results suggest that contaminant impact might differ according to the reproduction cycle stage. The effect of confounding factors on biomarker variations should be further investigated to have a deeper knowledge of metabolism responses under laboratory conditions.

INOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer.

Simple SummaryThe role of Inducible Nitric Oxygen Synthase (iNOS) in the progression of human malignancies is obscure. We studied the expression patterns of iNOS in non-small-cell lung cancer. iNOS was expressed by cancer cells and cancer-associated fibroblasts. None of these patterns, however, are related to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing tumor-infiltrating lymphocytes (iNOS+TILs) occurred in 48% of cases. This was related to low Hypoxia-Inducible Factor 1α (HIF1α) and better overall survival. Expression of Programmed death-ligand 1 PD-L1, however, mitigates the beneficial effect of the presence of iNOS+TIL. An important role of iNOS in anti-neoplastic lymphocyte biology has been brought forward, supporting iNOS+TILs as putative immune response markers.Background: Inducible Nitric Oxygen Synthase (iNOS) promotes the generation of NO in tissues. Its role in tumor progression and immune response is unclear. Methods: The immunohistochemical expression patterns of iNOS were studied in a series of 98 tissue samples of non-small-cell lung carcinoma (NSCLC), in parallel with the expression of hypoxia and anaerobic metabolism markers, PD-L1 and tumor-infiltrating lymphocytes (TILs). Results: iNOS is expressed by cancer cells in 19/98 (19.4%), while extensive expression by cancer-associated fibroblasts occurs in 8/98 (8.2%) cases. None of these patterns relate to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing TILs (iNOS+TILs) occurs in 47/98 (48%) cases. This is related to low Hypoxia-Inducible Factor 1α (HIF1α), high PD-L1 expression and a better overall survival (p = 0.002). Expression of PD-L1, however, mitigates the beneficial effect of the presence of iNOS+TIL. Conclusions: Extensive expression of iNOS by TILs occurs in approximately 50% of NSCLCs, and this is significantly related to an improved overall survival. This brings forward the role of iNOS in anti-neoplastic lymphocyte biology, supporting iNOS+TILs as a putative marker of immune response. The value of this biomarker as a predictive and treatment-guiding tool for tumor immunotherapy demands further investigation.

Anaerobic Metabolism Markers as a Guide of Resuscitation Effort and Mortality Benefit in Septic Shock Among Egyptian Population

Introduction: Venous-to-arterial carbon dioxide pressure and ratio of carbon dioxide gap divided by difference in arterial-venous oxygen content might be relevant in septic shock management. The aim of this study was to evaluate whether carbon dioxide gap and ratio of carbon dioxide gap divided by difference in oxygen content following septic shock resuscitation could predict mortality. Methods: Fifty septic shock patients were included in this study. Arterial and central venous blood gas samples were measured before and 6 hours following fluid resuscitation and vasopressors. Results: Our study population was 61.6 ± 7.4 years (31 males). Thirty-three patients survived. Paired comparisons in nonsurvivors showed worsening hemodynamics, carbon dioxide gap, ratio of carbon dioxide gap divided by difference in oxygen content, and lactate clearance. Mortality prediction cutoffs for lactate (40 mg/dl) with sensitivity (88.2%) and specificity (78.8%), carbon dioxide gap (6 mmHg) with sensitivity (94.1%) and specificity (63.6%) and ratio of carbon dioxide gap divided by difference in oxygen content (1.6) with sensitivity (88.2%) and specificity (60.6%). Combined lactate and the ratio of carbon dioxide gap divided by difference in oxygen content had sensitivity of 88.2% and specificity of 93.9%. Combined lactate and carbon dioxide gap had sensitivity of 82.4% and specificity of 90.9%. Discussion: Changes in carbon dioxide gap and ratio of carbon dioxide gap divided by difference in arterial-venous oxygen content during resuscitation of septic shock were related to in-hospital mortality. Adding carbon dioxide gap and the ratio of carbon dioxide gap divided by difference in arterial-venous oxygen content to lactate increased the accuracy of mortality prediction.

Predicting postoperative complications with the respiratory exchange ratio after high-risk noncardiac surgery: A prospective cohort study.

The respiratory exchange ratio (RER), defined as the ratio of CO2 production (VCO2) to O2 consumption (VO2), is reported to be a noninvasive marker of anaerobic metabolism. The intubated, ventilated patient's inspired and expired fractions of O2 and CO2 (FiO2, FeO2, FiCO2 and FeCO2) are monitored in the operating room and can be used to calculate RER. To investigating the ability of the RER to predict postoperative complications. An observational, prospective study. Two French university hospitals between March 2017 and September 2018. A total of 110 patients undergoing noncardiac high-risk surgery. The RER was calculated as (FeCO2 - FiCO2)/(FiO2 - FeO2) at five time points during the operation. The primary endpoint was at the end of the surgery. The secondary endpoints were systemic oxygenation indices (pCO2 gap, pCO2 gap/arteriovenous difference in O2 ratio, central venous oxygen saturation) and the arterial lactate level at the end of the surgery. Complications were classified according to the European Peri-operative Clinical Outcome definitions. Postoperative complications occurred in 35 patients (34%). The median [interquartile range] RER at the end of surgery was significantly greater in the subgroup with complications, 1.06 [0.84 to 1.35] than in the subgroup without complications, 0.81 [0.75 to 0.91], and correlated significantly with the arterial lactate (r = 0.31, P < 0.001) and VO2 (r = -0.23, P = 0.001). Analysis of the area under the receiver operating characteristic curve for the predictive value of RER for postoperative complications revealed a value of 0.77 [95% confidence interval (CI) 0.69 to 0.88, P = 0.001]. The best cut-off for the RER was 0.94, with a sensitivity of 71% (95% CI 54 to 85) and a specificity of 79% (95% CI 68 to 88). As a putative noninvasive marker of tissue hypoperfusion and anaerobic metabolism, the RER can be used to predict complications following high-risk surgery. ClinicalTrials.gov identifier: NCT03471962.

Anoxia tolerance in the sea cucumbers Parastichopus californicus and Cucumaria miniata reflects habitat use

Natural fluctuations in dissolved oxygen are an important physiological challenge faced by marine organisms. This is particularly true of intertidal species that may become trapped in bodies of water where oxygen becomes rapidly depleted, or which may be emersed and exposed to elevated oxygen, but without respiratory organs adapted for uptake of oxygen from air. We sought to determine whether oxygen handling approaches differ in two species of sea cucumber, Cucumaria miniata and Parastichopus californicus, which inhabit distinct niches that vary in dissolved oxygen profiles. C. miniata occupies the rocky intertidal zone and thus experiences daily oscillations in oxygen content, whereas P. californicus inhabits the more oxygen stable, subtidal zone. Using closed chamber respirometry, our data showed that C. miniata have a higher basal metabolic rate than P. californicus, attributed to continuous filter-feeding, a phenomenon that contrasts with the sporadic feeding habits of the sediment-feeding P. californicus. Exposure to 6-h of anoxia or 6-h of emersion had no effect on coelomic fluid glucose concentrations in either species, however P. californicus body wall glucose concentrations increased ~6-fold relative to immersed normoxic controls under both treatments. Lactate production, a marker of anaerobic metabolism, was unaltered in both species under both anoxia and emersion conditions. These data demonstrate that habitat influences anoxia tolerance in sea cucumbers, with the intertidal C. miniata displaying a higher tolerance to both low dissolved oxygen and emersion, than the subtidal species, P. californicus.

Abstract 191: Selective Frontal Lobe Metabolic Dysfunction After Sub-arachnoid Hemorrhage

Aneurysmal SAH results in high morbidity. Patients who make a good neurological recovery report significant neuropsychological impairment such as loss of motivation, interests, and concentration, all of which are commonly associated with frontal lobe dysfunction. We hypothesize that subclinical frontal lobe injury occurs in neurologically intact SAH patients and may be identified by measuring brain energy metabolism using regional N-acetyl aspartate (NAA) as an imaging marker of neuronal integrity and mitochondrial function, and CSF lactate, as a marker of anaerobic metabolism. We utilized MR Spectroscopy (MRS) to measure regional NAA in SAH patients who had suffered neither cerebral infarction nor neurological deficits. Only patients who underwent endovascular aneurysm coiling were included. Measurements were made in frontal, temporal, occipital lobes, lateral ventricles, and averaged in each hemisphere from 3 slices. Matching ROIs were placed on the most proximate CT perfusion maps to measure corresponding rCBF. MR spectra were compared to controls from our data library (7 subjects) and to rCBF. Average age was 58 years, Hunt Hess score was 2.43±1.09, modified Fisher score was 2.79±1.05. 3 patients had DCI and none had cerebral infarction. Median GCS at discharge was 15. MRS was done at 9.93±7.73 days from admission. 1 patient had no MRS data, 3 patients had no CT perfusion. SAH patients demonstrated significantly reduced NAA/RMS in frontal lobes (16.18±4.96 vs. 20.93±5.56, p=0.042) but not in temporal (16.49±4.37 vs. 19.37±4.38, p=0.09) or occipital lobes (20.62±4.50 vs. 21.05±4.23, p=0.41). CSF lactate was significantly higher in SAH patients (7.74±2.27 vs. 4.02±0.76, p=0.001). NAA/RMS did not correlate with CBF in pooled data (R 2 =0.02, p=0.40) or in frontal lobe rCBF (R 2 =0.001, p=0.92); nor with CSF lactate (R 2 =0.02, p=0.53). Total frontal lobe NAA is selectively reduced and CSF lactate is elevated in neurologically intact survivors after SAH. This preliminary data is suggestive of energy depletion and subclinical brain injury, which appears to be independent of cerebral blood flow. In addition to validating this pilot data, we will study the association with cognitive impairment in these patients.

Tethered Cord Syndrome–A Study of the Short-Term Effects of Surgical Detethering on Markers of Neuronal Injury and Electrophysiologic Parameters

Several studies have assessed clinical and radiologic outcomes after detethering of the cord for tethered cord syndrome (TCS). However, no data regarding the impact of detethering on the metabolism or electrophysiologic functioning of the cord are available. The aim of this study was to assess the changes in the cerebrospinal fluid (CSF) levels of markers of neuronal injury and alterations in the electrophysiologic functioning of the spinal cord after detethering. This prospective study included patients with congenital TCS. Patients underwent clinical assessment, magnetic resonance imaging, somatosensory evoked potentials (SSEP) study, and CSF biochemical analysis (to estimate lactate, glial fibrillary acidic protein, and S100B levels), before and 3 months after surgery. Clinical and radiologic outcomes were assessed. We studied changes in biochemical and electrophysiologic parameters before and after detethering as surrogate markers for the effects of this intervention. Twenty-one patients were recruited over 2 years. Detethering led to clinical improvement in 75% of patients with motor deficits, 60% of patients with bladder symptoms, and 50% of patients with gait problems. At 3 months follow-up, 43% (median) of the preoperative vertical tethering was found to be corrected. There was significant reduction in CSF lactate, glial fibrillary acidic protein, and S100B levels as well as a significant decrease in the latencies of the SSEP waves 3 months after surgery. Surgical detethering led to a reduction in the CSF levels of the markers of anaerobic metabolism and neuronal injury. There was also a reduction in the latencies of the SSEP waves, indicating better electrophysiologic functioning of the cord.

Hypoxia-inducible proteins HIF1α and lactate dehydrogenase LDH5, key markers of anaerobic metabolism, relate with stem cell markers and poor post-radiotherapy outcome in bladder cancer

Purpose: To assess whether anaerobic metabolism, proliferation activity and stem cell content are linked with radioresistance in bladder cancer. Materials and methods: Tissue sections from 66 patients with invasive transitional cell bladder cancer treated with hypofractionated accelerated radiotherapy, was immunohistochemically analyzed for the Hypoxia-Inducible Factor 1α (HIF1α) and the anaerobic glycolysis enzyme lactate dehydrogenase 5 (LDH5). Proliferation index (Ki-67) and stem-cell marker (cluster of differentiation CD44, aldehyde dehydrogenase ALDH1) expression was also examined. Results: Both HIF1α and LDH5 expression were linked with high CD44 stem cell population (p = 0.001 and 0.05, respectively), while high Ki-67 proliferation index was linked with nuclear LDH5 expression (p = 0.03) and high histological grade (p = 0.02). A strong significant association of HIF1α (p = 0.0009) and of LDH5 (p < 0.0001) with poor local relapse free survival (LRFS) was noted, which was also confirmed in multivariate analysis. A significant association with overall survival was also noted. Silencing of lactate dehydrogenase LDHA gene in the human RT112 bladder cancer cell line, or exposure to oxamate (LDH activity inhibitor), resulted in strong radio-sensitization. Conclusions: HIF1α and LDH5 are markers of poor outcome in patients with bladder cancer treated with radiotherapy. Blockage of anaerobic metabolism may prove of importance in clinical radiotherapy.

Prognostic value of gasometric parameters of carbon dioxide in resuscitation of septic patients. A bibliography review

The anaerobic metabolism is the cornerstone in physiopathology of septic shock. Nowadays we have both the central or mixed venous oxigen saturation and lactate levels to monitoring the metabolism in septic patients. Some studies have shown that normalisation of systemic haemodynamic and oxygen metabolism variables not prevent progression to multiorgan damage and death.Recently has been proposed the venous-to-arterial carbon dioxide difference (ΔpvaCO2) as an alternative marker of tissue hypoperfusion, like Cardiac Index. High ΔpvaCO2 predicts adverse outcomes. Also has been proposed both, the ratio between the ΔpvaCO2 and arterial-to-venous oxygen content difference (ΔCavO2): ΔpvaCO2/ΔCavO2; and, the ratio between venous-to-arterial carbon dioxide difference (ΔCvaCO2) and ΔCavO2: ΔCvaCO2/ΔCavO2, as markers of anaerobic metabolism. Both of high ratios are related to high levels of lactate and worse prognosis. Therefore in patients with sepsis the combination of markers of resuscitation could be important to improve the outcomes.

Valor pronóstico de los parámetros gasométricos del dióxido de carbono en pacientes con sepsis. Una revisión bibliográfica

The anaerobic metabolism is the cornerstone in physiopathology of septic shock. Nowadays we have both the central or mixed venous oxigen saturation and lactate levels to monitoring the metabolism in septic patients. Some studies have shown that normalization of systemic hemodynamic and oxygen metabolism variables not prevent progression to multiorgan damage and death.Recently has been proposed the venous-to-arterial carbon dioxide difference (ΔpvaCO2) as an alternative marker of tissue hypoperfusion, like Cardiac Index. High ΔpvaCO2 predicts adverse outcomes. Also has been proposed both, the ratio between the ΔpvaCO2 and arterial-to-venous oxygen content difference (ΔCavO2): ΔpvaCO2/ΔCavO2; and, the ratio between venous-to-arterial carbon dioxide difference (ΔCvaCO2) and ΔCavO2: ΔCvaCO2/ΔCavO2, as markers of anaerobic metabolism. Both of high ratios are related to high levels of lactate and worse prognosis. Therefore in patients with sepsis the combination of markers of resuscitation could be important to improve the outcomes.

Pharmacological postconditioning by sevoflurane during cardiac surgery

Optimization of myocardial protection during cardiac surgery with a long period of anoxia infarction using sevoflurane postconditioning of myocardium. to develop the optimal pharmacological postconditioning protocol with sevoflurane for infarction patients ,undergoing cardiac surgery. Two groups were formedfor this study: CON] 00 (n-32) with aortic cross-clamping time 114±15 min and SEV100 group (n-34), where the myocardium anoxia was 119±22 minutes. According to previously developed in the pilot study Protocol, we added sevofturane in the circuit of extracorporeal circulation in a dose of 2.0 vol. % 20 minutes before removing the clamp from the aorta and the first 20 min of reperfusion in the group SE V100. In the group CON1 00 pharnacological postconditioning wasn't conducted. To assess the adequacy of the cardioprotection against ischemic damage in operated patients, we used the following clinical and laboratory parameters: changing the level of troponin T; the concentration of lactate and glucose as a marker of severity of anaerobic metabolism; concentration of proinflammatory cytokines IL-6, IL-8, TNF-alpha in blood serum as reperfusion injury markers. Also we used the registration of central hemodynamics data: measuring the mean invasive blood pressure; central venous pressure; Cardiac output was measured by the method of transesophageal echocardiography TEEcho-CG, calculated left ventricular ejection fraction by Simpson. We evaluated the clinical course of the perioperative period: incidence ofperioperative myocardial ischemia; the need and the duration ofuse of cardiotonic drugs in the perioperative period; the incidence of reperfusion arrhythmias; the frequency of self-recovery heart rate. According to the results of anaerobic metabolism markers, we can conclude that the period of the myocardium anoxia ofpatients in both groups experienced no significant difference. However; a completely different pattern was observed when comparing the proinflammatory cytokines, such as IL-6, IL-8, TNF-a. This confirms that the group SEV] 00 survived the reperfusion is much better than the group CON100. Instrumental examination also showed that the group ofpatients in which pharmacological postconditioning with sevofturane was held signficantly better suffered ischemia and reperfiision injury compared to control group. Self-recovery heart rate after removing the aorta clamp in the group CON100 was observed in 81%, in group SEV100 same - 93%. Similarly, the frequency of myocardial ischemia episodes on the ECG in reperfusion period was two times lower in the group SEV100 compared with group CON100 - 5.8% and 12.5% respectively. Reperfusion arrhythmia is almost 3 times more frequent in the group CON100 - 21,8%, in the group SEV100, where he conducted pharmacological postconditioning with sevoflurane is 8.8%.. Combined with sevoflurane cardioprotection FPC has a much better resistance to myocardial ischemia-reperfusion injury in patients with myocardial infarction time over 100 minutes than monoprotection with cardioplegic solution "Console ". This method can be recommended as an additional method ofprotection against myocardial ischemia-reperfusion injury.

Scaling matters: incorporating body composition into Weddell seal seasonal oxygen store comparisons reveals maintenance of aerobic capacities

Adult Weddell seals (Leptonychotes weddellii) haul-out on the ice in October/November (austral spring) for the breeding season and reduce foraging activities for ~4 months until their molt in the austral fall (January/February). After these periods, animals are at their leanest and resume actively foraging for the austral winter. In mammals, decreased exercise and hypoxia exposure typically lead to decreased production of O2-carrying proteins and muscle wasting, while endurance training increases aerobic potential. To test whether similar effects were present in marine mammals, this study compared the physiology of 53 post-molt female Weddell seals in the austral fall to 47 pre-breeding females during the spring in McMurdo Sound, Antarctica. Once body mass and condition (lipid) were controlled for, there were no seasonal changes in total body oxygen (TBO2) stores. Within each season, hematocrit and hemoglobin values were negatively correlated with animal size, and larger animals had lower mass-specific TBO2 stores. But because larger seals had lower mass-specific metabolic rates, their calculated aerobic dive limit was similar to smaller seals. Indicators of muscular efficiency, myosin heavy chain composition, myoglobin concentrations, and aerobic enzyme activities (citrate synthase and β-hydroxyacyl CoA dehydrogenase) were likewise maintained across the year. The preservation of aerobic capacity is likely critical to foraging capabilities, so that following the molt Weddell seals can rapidly regain body mass at the start of winter foraging. In contrast, muscle lactate dehydrogenase activity, a marker of anaerobic metabolism, exhibited seasonal plasticity in this diving top predator and was lowest after the summer period of reduced activity.

Lactate and Venoarterial Carbon Dioxide Difference/Arterial-Venous Oxygen Difference Ratio, but Not Central Venous Oxygen Saturation, Predict Increase in Oxygen Consumption in Fluid Responders*

During circulatory failure, the ultimate goal of treatments that increase cardiac output is to reduce tissue hypoxia. This can only occur if oxygen consumption depends on oxygen delivery. We compared the ability of central venous oxygen saturation and markers of anaerobic metabolism to predict whether a fluid-induced increase in oxygen delivery results in an increase in oxygen consumption. Prospective study. ICU. Fifty-one patients with an acute circulatory failure (78% of septic origin). Before and after a volume expansion (500 mL of saline), we measured cardiac index, o2- and Co2-derived variables and lactate. Volume expansion increased cardiac index ≥ 15% in 49% of patients ("volume-responders"). Oxygen delivery significantly increased in these 25 patients (+32% ± 16%, p < 0.0001). An increase in oxygen consumption ≥ 15% concomitantly occurred in 56% of these 25 volume-responders (+38% ± 28%). Compared with the volume-responders in whom oxygen consumption did not increase, the volume-responders in whom oxygen consumption increased ≥ 15% were characterized by a higher lactate (2.3 ± 1.1 mmol/L vs. 5.5 ± 4.0 mmol/L, respectively) and a higher ratio of the veno-arterial carbon dioxide tension difference (P(v - a)Co2) over the arteriovenous oxygen content difference (C(a - v)o2). A fluid-induced increase in oxygen consumption greater than or equal to 15% was not predicted by baseline central venous oxygen saturation but by high baseline lactate and (P(v - a)Co2/C(a - v)o2 ratio (areas under the receiving operating characteristics curves: 0.68 ± 0.11, 0.94 ± 0.05, and 0.91 ± 0.06). In volume-nonresponders, volume expansion did not significantly change cardiac index, but the oxygen delivery decreased due to a hemodilution-induced decrease in hematocrit. In volume-responders, unlike markers of anaerobic metabolism, central venous oxygen saturation did not allow the prediction of whether a fluid-induced increase in oxygen delivery would result in an increase in oxygen consumption. This suggests that along with indicators of volume-responsiveness, the indicators of anaerobic metabolism should be considered instead of central venous oxygen saturation for starting hemodynamic resuscitation.

Low Oxygen Tension Enhances Hepatitis C Virus Replication

Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells. In vitro propagation of hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV production in actively dividing or differentiating human hepatoma cells cultured under low or atmospheric oxygen tensions. By using both HCV replicons and infection-based assays, low oxygen was found to enhance HCV RNA replication whereas virus entry and RNA translation were not affected. Hypoxia signaling pathway-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses revealed an upregulation of genes related to hypoxic stress, glycolytic metabolism, cell growth, and proliferation when cells were kept under low (3% [vol/vol]) oxygen tension, likely reflecting cell adaptation to anaerobic conditions. Interestingly, hypoxia-mediated enhancement of HCV replication correlated directly with the increase in anaerobic glycolysis and creatine kinase B (CKB) activity that leads to elevated ATP production. Surprisingly, activation of hypoxia-inducible factor alpha (HIF-α) was not involved in the elevation of HCV replication. Instead, a number of oncogenes known to be associated with glycolysis were upregulated and evidence that these oncogenes contribute to hypoxia-mediated enhancement of HCV replication was obtained. Finally, in liver biopsy specimens of HCV-infected patients, the levels of hypoxia and anaerobic metabolism markers correlated with HCV RNA levels. These results provide new insights into the impact of oxygen tension on the intricate HCV-host cell interaction.

Lactate dehydrogenase, Catalase, and Superoxide dismutase in Tumor Tissue of Breast Cancer Patients in Respect to Mammographic Findings

Lactate dehydrogenase (LDH), marker of anaerobic metabolism, is associated with highly invasive and metastatic breast cancer. Novel studies show that increased anaerobic metabolism (LDH), as well as activity of antioxidative enzymes (superoxide dismutase (SOD) and catalase (CAT)), is correlated with higher mammographic density, as known predictor of breast cancer risk. In this study, we measured LDH, MDH, and SOD activity in tumor and adjacent tissues of breast cancer patients by spectrophotometric assay. Mammograms were evaluated according to the American College of Radiology Breast Imaging Reporting and Data system. Mammographically dense breast tissue is associated with higher activity of LDH in tumor tissue of breast cancer patients. Moreover, patients with masses have significantly higher activity of LDH compared to patients with focal asymmetries or architectural distortion. Patients with spiculated mass margin had higher activity of LDH compared to patients with focal asymmetries or architectural distortion. Activity of LDH in patients significantly increases, while activity of CAT significantly decreases with the increase of BIRADS category. These results suggest that the association of activity of LDH and CAT in tumor tissue with mammographic characteristics could help in defining aggressive breast cancers.

Microdialysis in Early Detection of Temporary Pancreatic Ischemia in a Porcine Model

Background: Ischemic injury to the pancreas occurs in various clinical conditions. A method for online monitoring of pathophysiological events in pancreatic parenchyma is missing. Aims: To assess the timing of microdialysis (MD) technique response on temporary changes in pancreatic perfusion, and to evaluate the relationship between MD data and systemic markers of anaerobic metabolism and inflammation. Methods: In anaesthetized normoventilated pigs, MD probes were placed in right (control) and left (ischemic) pancreatic lobes, respectively. Following the clamping of the vessels, ischemia was verified by tissue oxygen tension (P_tiO₂) measurements. Results: P_tiO₂ decreased within 20 min after the clamping of the vessels, already returning to baseline levels at the first sampling point after the removal of the clamp. MD lactate levels increased, whereas pyruvate and glucose levels decreased at 20 min after the induction of ischemia. These trends continued until the end of ischemia and returned to baseline following reperfusion. Serum lactate, amylase and tumor necrosis factor-alpha levels decreased throughout the protocol time. Conclusion: MD data were in concordance with changes in P_tiO₂, which is indicative of local anaerobic metabolism. MD allowed the detection of pathophysiological processes within the ischemic pancreas at a stage when no elevations of systemic markers of ischemia or inflammation were observed.

Energetics of paraplegic cycling: Adaptations to 12 months of high volume training

The efficiency of functional electrical-stimulation (FES) cycling in spinal cord injured and anaesthetised able-bodied cyclists has been found to be about one third of that reported during volitional cycling. The stimulation paradigm itself appears to be the main source of this inefficiency. It is unknown whether a period of high-volume training can induce adaptations that may influence the metabolic and electrical cost of FES cycling. 11 individuals with paraplegia completed a 12-month, home-based, progressive FES cycle training programme (up to 5 × 60 min per wk). Stimulation cost, oxygen cost, efficiency and markers of anaerobic metabolism were determined before and after 6 and 12 months of training, during constant work-rate tests. Oxygen cost and efficiency did not significantly change after training. Total stimulation cost and blood lactate values reduced overall, while respiratory exchange ratios remained relatively high. The high metabolic cost of FES cycling is a result of non-physiological recruitment of predominantly fast muscle fibres. The electrical cost of cycling reduced by 37%, probably due to motor unit hypertrophy, and lactate oxidation capacity improved.