scholarly journals Peritubular Capillary Oxygen Consumption in Sepsis-Induced AKI: Multi-Parametric Photoacoustic Microscopy

Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 621-625
Author(s):  
Nabin Poudel ◽  
Shuqiu Zheng ◽  
Colleen M. Schinderle ◽  
Naidi Sun ◽  
Song Hu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Energy Demand ◽  
Oxygen Metabolism ◽  
High Energy ◽  
Renal Hemodynamics ◽  
Metabolic Reprogramming ◽  
Acoustic Microscopy ◽  
Physiological Status ◽  
Outer Medulla

Understanding and measuring parameters responsible for the pathogenesis of sepsis-induced AKI (SI-AKI) is critical in developing therapies. Blood flow to the kidney is heterogeneous, partly due to the existence of dynamic networks of capillaries in various regions, responding differentially to oxygen demand in cortex versus medulla. High energy demand regions, especially the outer medulla, are susceptible to hypoxia and subject to damage during SI-AKI. Proximal tubule epithelial cells in the cortex and the outer medulla can also undergo metabolic reprogramming during SI-AKI to maintain basal physiological status and to avoid potential damage. Current data on the assessment of renal hemodynamics and oxygen metabolism during sepsis is limited. Preclinical and clinical studies show changes in renal hemodynamics associated with SI-AKI, and in clinical settings, interventions to manage renal hemodynamics seem to help improve disease outcomes in some cases. Lack of proper tools to assess temporospatial changes in peritubular blood flow and tissue oxygen metabolism is a barrier to our ability to understand microcirculatory dynamics and oxygen consumption and their role in the pathogenesis of SI-AKI. Current tools to assess renal oxygenation are limited in their usability as these cannot perform continuous simultaneous measurement of renal hemodynamics and oxygen metabolism. Multi-parametric photo-acoustic microscopy (PAM) is a new tool that can measure real-time changes in microhemodynamics and oxygen metabolism. Use of multi-parametric PAM in combination with advanced intravital imaging techniques has the potential to understand the contribution of microhemodynamic and tissue oxygenation alterations to SI-AKI.

scholarly journals Transmural distribution of metabolic abnormalities and glycolytic activity during dobutamine-induced demand ischemia

2008 ◽  
Vol 294 (6) ◽  
pp. H2680-H2686 ◽  
Author(s):  
Mohammad N. Jameel ◽  
Xiaohong Wang ◽  
Marcel H. J. Eijgelshoven ◽  
Abdul Mansoor ◽  
Jianyi Zhang
Keyword(s):  
Blood Flow ◽  
Coronary Stenosis ◽  
Energy Demand ◽  
Weight Ratio ◽  
Dry Weight ◽  
High Energy ◽  
Left Ventricular ◽  
Cardiac Work ◽  
Induced Demand ◽  
Systolic Thickening

The heterogeneity across the left ventricular wall is characterized by higher rates of oxygen consumption, systolic thickening fraction, myocardial perfusion, and lower energetic state in the subendocardial layers (ENDO). During dobutamine stimulation-induced demand ischemia, the transmural distribution of energy demand and metabolic markers of ischemia are not known. In this study, hemodynamics, transmural high-energy phosphate (HEP), 2-deoxyglucose-6-phosphate (2-DGP) levels, and myocardial blood flow (MBF) were determined under basal conditions, during dobutamine infusion (DOB: 20 μg·kg−1·min−1 iv), and during coronary stenosis + DOB + 2-deoxyglucose (2-DG) infusion. DOB increased rate pressure products (RPP) and MBF significantly without affecting the subendocardial-to-subepicardial blood flow ratio (ENDO/EPI) or HEP levels. During coronary stenosis + DOB + 2-DG infusion, RPP, ischemic zone (IZ) MBF, and ENDO/EPI decreased significantly. The IZ ratio of creatine phosphate-to-ATP decreased significantly [2.30 ± 0.14, 2.06 ± 0.13, and 2.04 ± 0.11 to 1.77 ± 0.12, 1.70 ± 0.11, and 1.72 ± 0.12 for EPI, midmyocardial (MID), and ENDO, respectively], and 2-DGP accumulated in all layers, as evidenced by the 2-DGP/PCr (0.55 ± 0.12, 0.52 ± 0.10, and 0.37 ± 0.08 for EPI, MID, and ENDO, respectively; P < 0.05, EPI > ENDO). In the IZ the wet weight-to-dry weight ratio was significantly increased compared with the normal zone (5.9 ± 0.5 vs. 4.4 ± 0.4; P < 0.05). Thus, in the stenotic perfused bed, during dobutamine-induced high cardiac work state, despite higher blood flow, the subepicardial layers showed the greater metabolic changes characterized by a shift toward higher carbohydrate metabolism, suggesting that a homeostatic response to high-cardiac work state is characterized by more glucose utilization in energy metabolism.

Abstract P430: VSMCs Increase Glutamine Utilization For Energy Metabolism During Obesity

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Krystal M Roggerson ◽  
Sharon Francis
Keyword(s):  
Oxygen Consumption ◽  
Energy Metabolism ◽  
High Fat Diet ◽  
Vascular Remodeling ◽  
Energy Demand ◽  
Critical Role ◽  
Fold Increase ◽  
Metabolic Reprogramming ◽  
High Fat ◽  
Low Fat

Obesity increases the risk of developing cardiovascular disease through vascular remodeling though the underlying mechanisms are not entirely understood. However, metabolic fuel partitioning and mitochondrial flexibility during energy metabolism may play a critical role. We demonstrated serum and glucocorticoid-inducible kinase 1 (SGK-1) is up-regulated in the vasculature of diet-induced obese mice and that SGK-1 deletion is protective against obesity-induced vascular remodeling by metabolically reprogramming vascular smooth muscle cell (VSMC) energy metabolism towards oxidative phosphorylation (OXPHOS) and away from glycolysis. Mitochondrial substrate availability and utilization of the primary metabolic fuels glucose, long chain fatty acids (LCFAs) and glutamine can drive metabolic reprogramming. Therefore, alterations in fuel utilization may contribute to vascular remodeling during obesity. The purpose of this study was to examine SGK-1’s role in 1) fuel dependency: a cell’s reliance for a specific fuel and 2) fuel capacity: a cell’s ability to oxidize a specific fuel to meet cellular energy demand under low-fat and high-fat diet-induced obesity. Using the MitoXpress Oxygen Consumption assay which measures OXPHOS, primary VSMCs isolated from wildtype (WT) and SMC-specific SGK-1 knockout (smSGK-1 KO) mice fed a 10% kcal low-fat or 45% kcal high-fat diet for eight weeks were seeded in a 96-well plate at a density of 6x10 4 cells/well in culture medium. To assess fuel dependency, cells were treated with fuel pathway inhibitors UK5099, Etomoxir or BPTES to block glucose, LCFA or glutamine oxidation, respectively. To measure fuel capacity, VSMCs were treated with a combination of two pathway inhibitors simultaneously. Next, samples were overlaid with a fluorescent extracellular oxygen consumption reagent, sealed with high-sensitivity mineral oil, then signals were read at 1.5-minute intervals for 2 hours at Ex/Em= 380/650 nm. Our results show WT VSMCs are exclusively glucose-dependent for OXPHOS regardless of dietary conditions. However, SGK-1 deletion induces a dependency for all three fuels for OXPHOS in VSMCs under low- and high-fat conditions. Even though WT and smSGK-1 KO VSMCs preferentially oxidized glucose for OXPHOS under low-fat conditions; SGK-1 deletion resulted in a 2.2-fold increase in glutamine capacity. Alternatively, WT VSMCs exposed to obesogenic conditions preferentially oxidized glutamine whereas SGK-1 deletion induced a nearly equal partitioning of all three fuels during obesity suggesting elevated mitochondrial flexibility. Overall, this study suggests SGK-1 increases glucose dependency for energy metabolism under physiological and obesogenic conditions. Also, increased glutamine utilization for OXPHOS during obesity may be an underlying cause of VSMC dysfunction and subsequent vascular impairment.

Adrenergic influences on cardiac function during ventricular fibrillation in isolated rat hearts

1991 ◽  
Vol 261 (5) ◽  
pp. H1452-H1456
Author(s):  
I. Derad ◽  
I. Funk ◽  
P. Pauschinger ◽  
J. Born
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Ventricular Fibrillation ◽  
Cardiac Function ◽  
Coronary Blood Flow ◽  
High Energy ◽  
High Energy Phosphates ◽  
Tissue Concentrations ◽  
Rat Hearts ◽  
Isolated Rat

Effects of norepinephrine (NE, 10(-6) M), epinephrine (E, 10(-6) M), and vehicle on coronary blood flow (CF), oxygen consumption, and lactate release were compared in 32 isolated rat hearts during 5 min of ventricular fibrillation (VF). After VF, tissue concentrations of ATP, AMP, creatinine phosphate (CP), and lactate were measured. Perfusion of treatments started 30 s after onset of VF and was maintained throughout VF. CF during VF was greater (P less than 0.005) during perfusion of E (mean +/- SE, 5.73 +/- 0.15 ml/min) than NE (5.06 +/- 0.32 ml/min) or vehicle (5.11 +/- 0.18 ml/min). Oxygen consumption during VF was higher during perfusion of E (29.5 +/- 0.9 microliters.min(-1).g wet heart wt(-1)) than vehicle (27.3 +/- 0.7 microliters.min(-1).g(-1); P less than 0.05); average oxygen consumption during NE (27.6 +/- 1.4 microliters.min(-1).g(-1)) and vehicle were comparable. After NE, but not E, tissue AMP concentrations were significantly increased, and CP concentrations were reduced compared with vehicle (P less than 0.05). Enhanced consumption of high-energy phosphates during NE suggests that there is also an enhanced demand for oxygen. However, unlike during E, during NE this demand is not met by an augmented CF. Thus, compared with E, NE treatment during VF may increase the risk of hypoxic damage.

scholarly journals Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target

2021 ◽  
Vol 22 (11) ◽  
pp. 5703
Author(s):  
Vittoria Infantino ◽  
Anna Santarsiero ◽  
Paolo Convertini ◽  
Simona Todisco ◽  
Vito Iacobazzi
Keyword(s):  
Cancer Cells ◽  
Energy Demand ◽  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Hypoxia Inducible Factor ◽  
Cancer Therapeutics ◽  
High Energy ◽  
Metabolic Reprogramming ◽  
Low Oxygen ◽  
Functional Changes

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underlies the metabolic and functional changes of cancer cells. Noteworthy, HIF-1 represents a promising target for novel cancer therapeutics. In this review, we summarize the molecular mechanisms underlying the interplay between HIF-1 and energetic metabolism, with a focus on mitochondria, of hypoxic cancer cells.

Cerebrospinal fluid production and its relationship to cerebral metabolism and cerebral blood flow

1959 ◽  
Vol 197 (4) ◽  
pp. 825-828 ◽  
Author(s):  
Edgar A. Bering
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cerebral Blood Flow ◽  
Oxygen Consumption ◽  
Choroid Plexus ◽  
Cerebral Metabolism ◽  
Oxygen Metabolism ◽  
Csf Flow ◽  
Constant Composition ◽  
Fluid Production

The cerebrospinal fluid production has been studied in the dog under conditions of maximum obtainable flow rates from the cisterna magna. Under these conditions the fluid had constant composition and was assumed to represent the cerebrospinal fluid in the intact state. Cerebral blood flow and cerebral oxygen consumption were measured by the method of Kety and Schmidt. The only significant correlations found were with oxygen consumption when the CSF flow rate was in terms of brain weight and with cerebral blood flow and cerebral vascular resistance when CSF flow was in terms of choroid plexus weight. A combined regression equation was calculated which satisfactorily accounted for the observed CSF flow: CSF cu mm/min. = .128 x CMRO2 x brain wgt. + 0.15 x CVR x choroid plexus wt. This suggested separate physiological processes, one correlated with oxygen metabolism and one with hydrodynamic factors of the cerebral blood flow. The data demonstrated that the choroid plexus alone could not have accounted for the entire CSF flow and some must have come from another source, presumably the brain.

scholarly journals Glucose Metabolic Dysfunction in Neurodegenerative Diseases—New Mechanistic Insights and the Potential of Hypoxia as a Prospective Therapy Targeting Metabolic Reprogramming

2021 ◽  
Vol 22 (11) ◽  
pp. 5887
Author(s):  
Rongrong Han ◽  
Jing Liang ◽  
Bing Zhou
Keyword(s):  
Glucose Metabolism ◽  
Neurodegenerative Disease ◽  
Energy Demand ◽  
High Energy ◽  
Adult Brain ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Normal Brain ◽  
Metabolic Dysfunction ◽  
Lateral Sclerosis

Glucose is the main circulating energy substrate for the adult brain. Owing to the high energy demand of nerve cells, glucose is actively oxidized to produce ATP and has a synergistic effect with mitochondria in metabolic pathways. The dysfunction of glucose metabolism inevitably disturbs the normal functioning of neurons, which is widely observed in neurodegenerative disease. Understanding the mechanisms of metabolic adaptation during disease progression has become a major focus of research, and interventions in these processes may relieve the neurons from degenerative stress. In this review, we highlight evidence of mitochondrial dysfunction, decreased glucose uptake, and diminished glucose metabolism in different neurodegeneration models such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). We also discuss how hypoxia, a metabolic reprogramming strategy linked to glucose metabolism in tumor cells and normal brain cells, and summarize the evidence for hypoxia as a putative therapy for general neurodegenerative disease.

Abstract 17303: Longitudinal Cerebral Oxygen Metabolism in Congenital Heart Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jessie Mei Lim ◽  
Davide Marini ◽  
Amandeep Saini ◽  
Stephanie Au-Young ◽  
Steven Fan ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Oxygen Consumption ◽  
Congenital Heart ◽  
Oxygen Metabolism ◽  
Cerebral Oxygen ◽  
Brain Growth ◽  
Cerebral Oxygen Metabolism ◽  
Cerebral Oxygen Consumption

Background: Brain growth differences are apparent between different types of cyanotic congenital heart disease, but the underlying mechanism remains unclear. Here, we explored and characterized longitudinal cerebral hemodynamic and oxygen metabolism profiles and their relationships to brain growth patterns in infants with single ventricle physiologies (SV) and transposition of the great arteries (TGA). We hypothesized that there are marked differences in cerebral oxygen metabolism in those with SV compared with TGA. Methods: Cerebral blood flow (CBF), oxygen delivery (CDO2) and consumption (CVO2) and brain growth were measured in 103 term newborns with SV and TGA using MRI at pre- and post-surgery and at follow-up. We measured whole brain size by segmenting a 3D steady state free precession acquisition. Cerebral blood flow was measured using phase contrast imaging of the neck vessels and cerebral venous blood oxygen saturation was derived from T2 oximetry of the superior sagittal sinus. TGAs were divided into those with and without ventricular septums. Results: CBF profiles were similar between the 3 lesion groups. Cerebral oxygen delivery trends increased but were not significantly different between cardiac groups. We observed that this may be mediated by different mechanisms: an increase in arterial saturation in TGAs, and an increase in hemoglobin concentration in SVs. Cerebral oxygen consumption in SV infants remained low (p = 0.54) while that of TGA increased over time (TGA IVS p < 0.001; TGA VSD p <0.001) (Fig. 1), mediated by an unchanging oxygen extraction fraction in SVs (p = 0.59). The SV cerebral oxygen consumption profile aligned with their declining brain weight z-score trajectory. Conclusions: In conclusion, there are characteristic differences in hemodynamic adaptations between SVs and TGAs. Changes in oxygen metabolism may be facilitating brain growth trajectories. This informs us of possible mechanisms involved during a time of critical brain development.

scholarly journals Effects of MK-801 and NBQX on Acute Recovery of Piglet Cerebral Metabolism after Hypothermic Circulatory Arrest

1994 ◽  
Vol 14 (1) ◽  
pp. 156-165 ◽  
Author(s):  
Mitsuru Aoki ◽  
Fumikazu Nomura ◽  
Michael E. Stromski ◽  
Miles K. Tsuji ◽  
James C. Fackler ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Oxygen Consumption ◽  
Cardiopulmonary Bypass ◽  
Circulatory Arrest ◽  
High Energy ◽  
Hypothermic Circulatory Arrest ◽  
Cerebral Oxygen ◽  
High Energy Phosphates ◽  
Mk 801

Brain protection during open heart surgery in the neonate and infant remains inadequate. Effects of the excitatory neurotransmitter antagonists MK-801 and NBQX on recovery of brain cellular energy state and metabolic rates were evaluated in 34 4-week-old piglets (10 MK-801, 10 NBQX, 14 controls) undergoing cardiopulmonary bypass and hypothermic circulatory arrest at 15°C nasopharyngeal temperature for 1 h, as is used clinically for repair of congenital heart defects. MK-801 (dizocilpine) (0.75 mg/kg) or NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F)quinoxaline] (25 mg/kg) was given intravenously before cardiopulmonary bypass. Equivalent doses were placed in the cardiopulmonary bypass prime plus continuous infusions after reperfusion (0.15 mg kg−1h−1 and 5 mg kg−1h−1). Changes in high-energy phosphate concentrations and pH were analyzed by magnetic resonance spectroscopy in 17 animals until 225 min after reperfusion. Cerebral blood flow determined by radioactive microspheres as well as cerebral oxygen and glucose consumption were studied in 17 other animals. Cerebral blood flow and oxygen consumption were depressed relative to control by both MK-801 and NBQX at baseline. Recovery of phosphocreatine (p = 0.010), ATP (p = 0.030), and intracellular pH (p = 0.004) was accelerated by MK-801 and retarded by NBQX over the 45 min of rewarming reperfusion and the first hour of normothermic reperfusion. The final recovery of ATP at 3 h and 45 min reperfusion was significantly reduced by NBQX (46 ± 26% baseline, mean ± SD) versus control (81 ± 19%) and MK-801 (75 ± 8%) (p = 0.030). Cerebral oxygen consumption recovered to 105 ± 30% baseline in group MK-801 and 94 ± 31% in control but only to 61 ± 22% in group NBQX (p = 0.070). Cerebral blood flow stayed significantly lower in group NBQX relative to control. Thus, MK-801 accelerates recovery of cerebral high-energy phosphates and metabolic rate after cardiopulmonary bypass and hypothermic circulatory arrest in the immature animal. At the dosage used NBQX exerts an adverse effect.

scholarly journals Neurovascular Coupling in Development and Disease: Focus on Astrocytes

2021 ◽  
Vol 9 ◽  
Author(s):  
Teresa L. Stackhouse ◽  
Anusha Mishra
Keyword(s):  
Blood Flow ◽  
Energy Demand ◽  
Neurovascular Unit ◽  
Neurovascular Coupling ◽  
Time Frame ◽  
Blood Oxygen Level Dependent ◽  
High Energy ◽  
Neural Activation ◽  
Blood Oxygen Level ◽  
Similar Time

Neurovascular coupling is a crucial mechanism that matches the high energy demand of the brain with a supply of energy substrates from the blood. Signaling within the neurovascular unit is responsible for activity-dependent changes in cerebral blood flow. The strength and reliability of neurovascular coupling form the basis of non-invasive human neuroimaging techniques, including blood oxygen level dependent (BOLD) functional magnetic resonance imaging. Interestingly, BOLD signals are negative in infants, indicating a mismatch between metabolism and blood flow upon neural activation; this response is the opposite of that observed in healthy adults where activity evokes a large oversupply of blood flow. Negative neurovascular coupling has also been observed in rodents at early postnatal stages, further implying that this is a process that matures during development. This rationale is consistent with the morphological maturation of the neurovascular unit, which occurs over a similar time frame. While neurons differentiate before birth, astrocytes differentiate postnatally in rodents and the maturation of their complex morphology during the first few weeks of life links them with synapses and the vasculature. The vascular network is also incomplete in neonates and matures in parallel with astrocytes. Here, we review the timeline of the structural maturation of the neurovascular unit with special emphasis on astrocytes and the vascular tree and what it implies for functional maturation of neurovascular coupling. We also discuss similarities between immature astrocytes during development and reactive astrocytes in disease, which are relevant to neurovascular coupling. Finally, we close by pointing out current gaps in knowledge that must be addressed to fully elucidate the mechanisms underlying neurovascular coupling maturation, with the expectation that this may also clarify astrocyte-dependent mechanisms of cerebrovascular impairment in neurodegenerative conditions in which reduced or negative neurovascular coupling is noted, such as stroke and Alzheimer’s disease.

Sign in / Sign up

Export Citation Format

Share Document