Regional blood flow and skeletal muscle energy status in endotoxemic rats

1987 ◽  
Vol 252 (5) ◽  
pp. E581-E587 ◽  
Author(s):  
M. M. Jepson ◽  
M. Cox ◽  
P. C. Bates ◽  
N. J. Rothwell ◽  
M. J. Stock ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Regional Blood Flow ◽  
High Energy ◽  
Whole Body ◽  
Sublethal Dose ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Energy Status ◽  
Brown Adipose

Endotoxins induce muscle wasting in part as a result of depressed protein synthesis. To investigate whether these changes reflect impaired energy transduction, blood flow, O2 extraction, and high-energy phosphates in muscle and whole-body O2 consumption (VO2) have been measured. VO2 was measured for 6h after an initial sublethal dose of endotoxin (Escherichia coli lipopolysaccharide 0.3 mg/100 g body wt sc) or saline and during 6h after a second dose 24 h later. In fed or fasted rats, VO2 was either increased or better maintained after endotoxin. In anesthetized fed rats 3-4 after the second dose of endotoxin VO2 was increased, and this was accompanied by increased blood flow to liver (hepatic arterial supply), kidney, and perirenal brown adipose tissue and a 57 and 64% decrease in flow to back and hindlimb muscle, respectively, with no change in any other organ. Hindlimb arteriovenous O2 was unchanged, indicating markedly decreased aerobic metabolism in muscle, and the contribution of the hindlimb to whole-body VO2 decreased by 46%. Adenosine 5'-triphosphate levels in muscle were unchanged in endotoxin-treated rats, and this was confirmed by topical nuclear magnetic resonance spectroscopy, which also showed muscle pH to be unchanged. These results show that although there is decreased blood flow and aerobic oxidation in muscle, adenosine 5'-triphosphate availability does not appear to be compromised so that the endotoxin-induced muscle catabolism and decreased protein synthesis must reflex some other mechanism.

scholarly journals Tirilazad Pretreatment Improves Early Cerebral Metabolic and Blood Flow Recovery from Hyperglycemic Ischemia

1995 ◽  
Vol 15 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Yuichi Maruki ◽  
Raymond C. Koehler ◽  
Jeffrey R. Kirsch ◽  
Kathleen K. Blizzard ◽  
Richard J. Traystman
Keyword(s):  
Lipid Peroxidation ◽  
Blood Flow ◽  
Intracranial Pressure ◽  
Intracellular Ph ◽  
High Energy ◽  
Vehicle Group ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Early Reperfusion ◽  
Tirilazad Mesylate

Acidosis may augment cerebral ischemic injury by promoting lipid peroxidation. We tested the hypothesis that when acidosis is augmented by hyperglycemia, pretreatment with the 21-aminosteroid tirilazad mesylate (U74006F), a potent inhibitor of lipid peroxidation in vitro, improves early cerebral metabolic recovery. In a randomized, blinded study, anesthetized dogs received either tirilazad mesylate (1 mg/kg plus 0.2 mg/kg/h; n = 8) or vehicle (n = 8). Hyperglycemia (400–500 mg/dl) was produced prior to 30 min of global incomplete cerebral ischemia. Intracellular pH and high energy phosphates were measured by phosphorus magnetic resonance spectroscopy. During ischemia, microsphere-determined CBF decreased to 8 ± 4 ml min−1 100 g−1 and intracellular pH decreased to 5.6 ± 0.2 in both groups. During the first 20 min of reperfusion, ATP partially recovered in the vehicle group to 57 ± 21% of baseline, but then declined progressively in association with elevated intracranial pressure. By 30 min, ATP recovery was greater in the tirilazad group (77 ± 35 vs. 36 ± 19%), although postischemic hyperemia was similar. By 45 min, the tirilazad group had a higher intracellular pH (6.5 ± 0.5 vs. 5.9 ± 0.6) and a lower intracranial pressure (18 ± 6 vs. 52 ± 24 mm Hg). By 180 min, blood flow and ATP were undetectable in seven of eight vehicle-treated dogs, whereas ATP was >67% and pH was >6.7 in six of eight tirilazad-treated dogs. Thus, tirilazad acts during early reperfusion to prevent secondary metabolic decay associated with severe acidotic ischemia. If tirilazad acts by inhibiting lipid peroxidation, then these data are consistent with extreme acidosis limiting recovery by a mechanism involving lipid peroxidation.

Myocardial oxygenation and high-energy phosphate levels during KATP channel blockade

2003 ◽  
Vol 285 (4) ◽  
pp. H1420-H1427 ◽  
Author(s):  
Jianyi Zhang ◽  
Arthur H. L. From ◽  
Kamil Ugurbil ◽  
Robert J. Bache
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
High Energy ◽  
Arterial Stenosis ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Channel Blockade ◽  
High Energy Phosphate ◽  
Similar Reduction ◽  
Myocardial Oxygenation

Inhibition of ATP-sensitive K+ (KATP) channel activity has previously been demonstrated to result in coronary vasoconstriction with decreased myocardial blood flow and loss of phosphocreatine (PCr). This study was performed to determine whether the high-energy phosphate abnormality during KATP channel blockade can be ascribed to oxygen insufficiency. Myocardial blood flow and oxygen extraction were measured in open-chest dogs during KATP channel blockade with intracoronary glibenclamide, whereas high-energy phosphates were examined with 31P magnetic resonance spectroscopy (MRS), and myocardial deoxymyoglobin (Mb-δ) was determined with 1H MRS. Glibenclamide resulted in a 20 ± 8% decrease of myocardial blood flow that was associated with a loss of phosphocreatine (PCr) and accumulation of inorganic phosphate. Mb-δ was undetectable during basal conditions but increased to 58 ± 5% of total myoglobin during glibenclamide administration. This degree of myoglobin desaturation during glibenclamide was far greater than we previously observed during a similar reduction of blood flow produced by a coronary stenosis (22% of myoglobin deoxygenated during stenosis). The findings suggest that reduction of coronary blood flow with an arterial stenosis was associated with a decrease of myocardial energy demands and that this response to hypoperfusion was inhibited by KATP channel blockade.

scholarly journals The relationships of high energy phosphates, tissue pH, and regional blood flow to diastolic distensibility in the ischemic dog myocardium.

1985 ◽  
Vol 57 (6) ◽  
pp. 822-835 ◽  
Author(s):  
S Momomura ◽  
J S Ingwall ◽  
J A Parker ◽  
P Sahagian ◽  
J J Ferguson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
High Energy ◽  
High Energy Phosphates ◽  
Tissue Ph

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

Blood flow and high-energy phosphates in microregions of left ventricular subendocardium

1981 ◽  
Vol 240 (5) ◽  
pp. H804-H810 ◽  
Author(s):  
H. D. Kleinert ◽  
H. R. Weiss
Keyword(s):  
Blood Flow ◽  
Linear Relationship ◽  
Tissue Perfusion ◽  
High Energy ◽  
Left Ventricular ◽  
Significant Loss ◽  
Tissue Blood Flow ◽  
High Energy Phosphates ◽  
Tissue Samples ◽  
Heterogeneous Distribution

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

Magnetic resonance spectroscopy of high-energy phosphates and lactate immediately after coronary artery bypass surgery

Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 328-333 ◽  
Author(s):  
D NF Harris ◽  
J A Wilson ◽  
S D Taylor-Robinson ◽  
K M Taylor
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Cerebral Ischaemia ◽  
Artery Bypass ◽  
High Energy ◽  
Jugular Bulb ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Intracellular Acidosis ◽  
High Incidence

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 ± 0.86 vs after: 2.57 ± 1.31; mean ± 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 ± 0.04 vs 7.16 ± 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 ± 0.37 vs 6.39 ± 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.

Metabolic and energy correlates of intracellular pH in progressive fatigue of squid (L. brevis) mantle muscle

1996 ◽  
Vol 271 (5) ◽  
pp. R1403-R1414 ◽  
Author(s):  
H. O. Portner ◽  
E. Finke ◽  
P. G. Lee
Keyword(s):  
Free Energy ◽  
Critical Velocity ◽  
Energy Levels ◽  
High Energy ◽  
Swimming Velocity ◽  
High Energy Phosphates ◽  
Energy Status ◽  
Intracellular Acidosis ◽  
Model Calculations

Squid (Lolliguncula brevis) were exercised at increasing swimming speeds to allow us to analyze the correlated changes in intracellular metabolic, acid-base, and energy status of the mantle musculature. Beyond a critical swimming velocity of 1.5 mantle lengths/s, an intracellular acidosis developed that was caused by an initial base loss from the cells, the onset of respiratory acidification, and, predominantly, octopine formation. The acidosis was correlated with decreasing levels of phospho-L-arginine and, thus, supported ATP buffering at the expense of the phosphagen. Monohydrogenphosphate, the actual substrate of glycogen phosphorylase accumulated, enabling glycogen degradation, despite progressive acidosis. In addition to octopine, succinate, and glycerophosphate accumulation, the onset of acidosis characterizes the critical velocity and indicates the transition to a non-steady-state time-limited situation. Accordingly, swimming above the critical velocity caused cellular energy levels (in vivo Gibbs free energy change of ATP hydrolysis) to fall. A minimal value was reached at about -45 kJ/mol. Model calculations demonstrate that changes in free Mg2+ levels only minimally affect ATP free energy, but minimum levels are relevant in maintaining functional concentrations of Mg(2+)-complexed adenylates. Model calculations also reveal that phosphagen breakdown enabled L. brevis to reach swimming speeds about three times higher than the critical velocity. Comparison of two offshore squid species (Loligo pealei and Illex illecebrosus) with the estuarine squid L.brevis indicates that the latter uses a strategy to delay the exploitation of high-energy phosphates and protect energy levels at higher than the minimum levels (-42 kJ/mol) characterizing fatigue in the other species. A more economical use of anaerobic resources and an early reduction in performance may enable L. brevis to tolerate more extreme environmental conditions in shallow estuarine waters and even hypoxic environments and to prevent a fatal depletion of energy stores.

Differential energetic response of brain vs. skeletal muscle upon glycemic variations in healthy humans

2008 ◽  
Vol 294 (1) ◽  
pp. R12-R16 ◽  
Author(s):  
Kerstin M. Oltmanns ◽  
Uwe H. Melchert ◽  
Harald G. Scholand-Engler ◽  
Maria C. Howitz ◽  
Bernd Schultes ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Underlying Mechanism ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
Energy Status ◽  
High Energy Phosphate ◽  
Available Energy ◽  
Healthy Humans ◽  
High Energy Phosphate Metabolism ◽  
The Brain

The brain regulates all metabolic processes within the organism, and therefore, its energy supply is preserved even during fasting. However, the underlying mechanism is unknown. Here, it is shown, using 31P-magnetic resonance spectroscopy that during short periods of hypoglycemia and hyperglycemia, the brain can rapidly increase its high-energy phosphate content, whereas there is no change in skeletal muscle. We investigated the key metabolites of high-energy phosphate metabolism as rapidly available energy stores by 31P MRS in brain and skeletal muscle of 17 healthy men. Measurements were performed at baseline and during dextrose or insulin-induced hyperglycemia and hypoglycemia. During hyperglycemia, phosphocreatine (PCr) concentrations increased significantly in the brain ( P = 0.013), while there was a similar trend in the hypopglycemic condition ( P = 0.055). Skeletal muscle content remained constant in both conditions ( P > 0.1). ANOVA analyses comparing changes from baseline to the respective glycemic plateau in brain (up to +15%) vs. muscle (up to −4%) revealed clear divergent effects in both conditions ( P < 0.05). These effects were reflected by PCr/Pi ratio ( P < 0.05). Total ATP concentrations revealed the observed divergency only during hyperglycemia ( P = 0.018). These data suggest that the brain, in contrast to peripheral organs, can activate some specific mechanisms to modulate its energy status during variations in glucose supply. A disturbance of these mechanisms may have far-reaching implications for metabolic dysregulation associated with obesity or diabetes mellitus.

Muscle metabolic responses to exercise above and below the “critical power” assessed using 31P-MRS

2008 ◽  
Vol 294 (2) ◽  
pp. R585-R593 ◽  
Author(s):  
Andrew M. Jones ◽  
Daryl P. Wilkerson ◽  
Fred DiMenna ◽  
Jonathan Fulford ◽  
David C. Poole
Keyword(s):  
Critical Power ◽  
Quadriceps Muscle ◽  
High Energy ◽  
Knee Extension ◽  
Work Rate ◽  
Metabolic Responses ◽  
Time To Exhaustion ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Constant Work Rate

We tested the hypothesis that the asymptote of the hyperbolic relationship between work rate and time to exhaustion during muscular exercise, the “critical power” (CP), represents the highest constant work rate that can be sustained without a progressive loss of homeostasis [as assessed using 31P magnetic resonance spectroscopy (MRS) measurements of muscle metabolites]. Six healthy male subjects initially completed single-leg knee-extension exercise at three to four different constant work rates to the limit of tolerance (range 3–18 min) for estimation of the CP (mean ± SD, 20 ± 2 W). Subsequently, the subjects exercised at work rates 10% below CP (<CP) for 20 min and 10% above CP (>CP) for as long as possible, while the metabolic responses in the contracting quadriceps muscle, i.e., phosphorylcreatine concentration ([PCr]), Pi concentration ([Pi]), and pH, were estimated using 31P-MRS. All subjects completed 20 min of <CP exercise without duress, whereas the limit of tolerance during >CP exercise was 14.7 ± 7.1 min. During <CP exercise, stable values for [PCr], [Pi], and pH were attained within 3 min after the onset of exercise, and there were no further significant changes in these variables (end-exercise values = 68 ± 11% of baseline [PCr], 314 ± 216% of baseline [Pi], and pH 7.01 ± 0.03). During >CP exercise, however, [PCr] continued to fall to the point of exhaustion and [Pi] and pH changed precipitously to values that are typically observed at the termination of high-intensity exhaustive exercise (end-exercise values = 26 ± 16% of baseline [PCr], 564 ± 167% of baseline [Pi], and pH 6.87 ± 0.10, all P < 0.05 vs. <CP exercise). These data support the hypothesis that the CP represents the highest constant work rate that can be sustained without a progressive depletion of muscle high-energy phosphates and a rapid accumulation of metabolites (i.e., H+ concentration and [Pi]), which have been associated with the fatigue process.

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