Ischemic conduction failure and energy metabolism in experimental diabetic neuropathy

1985 ◽  
Vol 248 (4) ◽  
pp. E457-E462 ◽  
Author(s):  
P. A. Low ◽  
K. Ward ◽  
J. D. Schmelzer ◽  
S. Brimijoin

We examined the effect of ischemia on nerve conduction in experimental diabetic neuropathy (EDN) and related electrophysiological changes to nerve adenosine triphosphate (ATP), creatine phosphate (CP), and lactate under anoxic conditions. Rats rendered diabetic with streptozotocin had a resistance to ischemic conduction block (RICB). Caudal nerve action potential (NAP) was well maintained for 10 min in controls and for 15 min in EDN, after which time NAP declined in both groups but more rapidly in normal rats. Time to 50% reduction in nerve ATP and CP was 10 and 3 min, respectively, in controls and delayed to 20 and 8 min in EDN. Rate of utilization of high-energy phosphate (approximately P) was linear for 5 min in controls to be followed by a progressive decline. In EDN rate of utilization of approximately P was linear to 15 min to be followed by a more gradual decline than in normal nerves. These findings suggest that the maintenance of nerve transmission in anoxic-ischemic states depends on anaerobic metabolism and that RICB in EDN is due in part to the ability of diabetic nerves to maintain a higher level of anaerobic glycolysis and for a longer time than normal nerves.

1978 ◽  
Vol 235 (5) ◽  
pp. H475-H481 ◽  
Author(s):  
J. M. Jarmakani ◽  
T. Nagatomo ◽  
M. Nakazawa ◽  
G. A. Langer

The effect of hypoxia on myocardial high-energy phosphate content in the newborn, 2-wk-old, and adult rabbit was determined and compared with mechanical function. Studies were done on the ventricular septum arterially perfused with Krebs-Henseleit bicarbonate buffer solution equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia) at 60 beats/min and 27 degrees C. In the adult, ATP concentration decreased to 68%, 56%, and 39% of control after 2, 30, and 60 min of hypoxia, respectively. After 30 min of hypoxia, ATP concentration was not different from control in the newborn but decreased to 82% of control in the 2-wk-old. After 2 min of hypoxia, creatine phosphate concentration decreased to 55% and 10% of control in the newborn and adult rabbit, respectively. Lactate production increased significantly during hypoxia and was greater in the newborn than in the adult. The data indicate that the newborn rabbit is capable of maintaining glycolysis and normal levels of myocardial ATP during hypoxia, which ensures normal myocardial mechanical function for longer periods than in the adult.


1976 ◽  
Vol 40 (6) ◽  
pp. 1004-1008 ◽  
Author(s):  
P. Kligfield ◽  
H. Horner ◽  
N. Brachfeld

Insertion of a flow pump into the Langendorff retrograde perfusion apparatus has permitted the production of stable, graded ischemia in hearts whose hemodynamic and metabolic response may be evaluated. Ventricular pressures were monitored with a modified balloon and catheter-tip manometer system, and oxygen consumption , lactate and glucose metabolism, and tissue high-energy phosphate stores measured. A 15-min stabilization period in 56 paced hearts was followed by 15 min of either full, 40, 30, 20, or 10% coronary flow, after which the ventricular tissue was freeze-clamped for tissue assay. Tissue creatine phosphate fell progressively from 23.7 in full flow hearts to 9.9 mumol/g dry wt after 90% reduction in flow. This was accompanied by a graded reduction in ATP from 20.3 to 14.0 mumol/g dry wt and a rise in AMP from 1.1 to 2.6 mumol/g dry wt. Tissue lactate rose progressively from 22.3 to 60.1 mumol/g dry wt. Hemodynamic function correlated with coronary flow. This preparation offers an opportunity to study pharmacological and metabolic interventions in ischemic heart disease.


1961 ◽  
Vol 200 (1) ◽  
pp. 182-186 ◽  
Author(s):  
Ruth D. Peterson ◽  
Clarissa H. Beatty ◽  
Rose M. Bocek

The metabolism of high-energy phosphates in a muscle fiber preparation and diaphragm has been investigated. During dissection the creatine phosphate (CrP) level of fibers decreased but was reconstituted during soaking to 61% of the in situ value and remained uncharged during incubation. Dissection and soaking did not affect the adenosinetriphosphate + adenosinediphosphate (ATP + ADP) levels but incubation caused small decreases. Similar decreases in CrP and ATP levels of diaphragm occurred during incubation. The decreases in the ATP levels in fibers and diaphragm correlated with decreases in adenine absorption. A concomitant shift occurred in the absorption peak of fiber media toward the absorption maximum of hypoxanthine. In contrast, the curves for diaphragm media showed a progressive shift toward the absorption maximum for uric acid. Uricase analyses demonstrated uric acid in diaphragm media. The mesothelial covering of the diaphragm was shown to have a separate and distinct metabolism which converts hypoxanthine to uric acid. Soaking the fibers in iced buffer instead of buffer at room temperature decreased the CrP levels after incubation, ATP values were unaffected.


1982 ◽  
Vol 33 (5) ◽  
pp. 453-458 ◽  
Author(s):  
Richard M. Engelman ◽  
William A. Dobbs ◽  
John H. Rousou ◽  
Mooideen K. Meeran

1985 ◽  
Vol 59 (3) ◽  
pp. 766-773 ◽  
Author(s):  
S. Kozlowski ◽  
Z. Brzezinska ◽  
B. Kruk ◽  
H. Kaciuba-Uscilko ◽  
J. E. Greenleaf ◽  
...  

The muscle contents of high-energy phosphates and their derivatives [ATP, ADP, AMP, creatine phosphate (CrP), and creatine], glycogen, some glycolytic intermediates, pyruvate, and lactate were compared in 11 dogs performing prolonged heavy exercise until exhaustion (at ambient temperature 20.0 +/- 1.0 degrees C) without and with trunk cooling using ice packs. Without cooling, dogs were able to run for 57 +/- 8 min, and their rectal (Tre) and muscle (Tm) temperatures increased to 41.8 +/- 0.2 and 43.0 +/- 0.2 degrees C, respectively. Compared with noncooling, duration of exercise with cooling was longer by approximately 45% while Tre and Tm at the time corresponding to the end of exercise without cooling were lower by 1.1 +/- 0.2 and 1.2 +/- 0.2 degrees C, respectively. The muscle contents of high-energy phosphates (ATP + CrP) decreased less, the rate of glycogen depletion was lower, and the increases in the contents of AMP, pyruvate, and lactate as well as in the muscle-to-blood lactate ratio were smaller. The muscle content of lactate was positively correlated with Tm. The data indicate that with higher body temperature equilibrium between high-energy phosphate breakdown and resynthesis was shifted to the lower values of ATP and CrP and glycolysis was accelerated. The results suggest that hyperthermia developing during prolonged muscular work exerts an adverse effect on muscle metabolism that may be relevant to limitation of endurance.


1966 ◽  
Vol 44 (7) ◽  
pp. 1015-1033 ◽  
Author(s):  
Doris I. Fraser ◽  
W. J. Dyer ◽  
H. M. Weinstein ◽  
J. R. Dingle ◽  
J. A. Hines

Muscular activity just before death critically affected the levels of glycolytic metabolites in the skeletal muscle of feeding, aquarium-held cod. Relaxed cod could be obtained by slow anesthetization without visible excitation; these contained very little lactate in the white muscle (7–28 mg/100 g), and exhibited high, uniformly distributed levels of high-energy phosphate compounds (about 17 μmoles acid-labile P/g plus equal or higher amounts of creatine phosphate). A trend to lower glycogen levels in the anterior portion of the fillet was indicated. Unexercised fish caught and killed with negligible struggling appeared to have undergone some antemortem activity. Compared with relaxed cod, they showed higher lactate levels (about 100 mg/100 g), much lower levels of creatine phosphate and other high-energy phosphate compounds, together with some ammonia. Again, glycogen was lower in the anterior than in the posterior portion. Exhaustion uniformly depleted energy reserves to low levels in the white muscle; in the red muscle, however, high glycogen levels were maintained, although the content of other glycolytic metabolites indicated partial activation of the glycolytic processes during the antemortem struggle. In all fish examined, levels of inorganic and total acid-soluble phosphorus were lower in the red than in the white muscle.


1994 ◽  
Vol 267 (3) ◽  
pp. H894-H904 ◽  
Author(s):  
J. Zhang ◽  
L. Shorr ◽  
M. Yoshiyama ◽  
H. Merkle ◽  
M. Garwood ◽  
...  

This study examines the hypothesis that high-energy phosphate (HEP) compound levels in unstimulated in vivo myocardium are defined by 1) the level of perfusion and 2) non-perfusion-dependent metabolic characteristics. This hypothesis was tested by determining 1) the effects of pharmacological hyperperfusion of functioning myocardium on transmural HEP compound distribution, contractile function, and myocardial oxygen consumption rate (MVO2) as well as 2) the effect of KCl cardioplegia on transmural myocardial HEP compound distribution. Creatine phosphate (CP) and ATP were measured across the anterior left ventricular wall using spatially localized 31P-nuclear magnetic resonance (NMR). At baseline, the CP-to-ATP (CP/ATP) ratio was significantly lower in the subendocardium than in the subepicardium. This transmural HEP gradient was abolished by hyperperfusion without significant effects on contractile function or MVO2. Similarly, KCl arrest significantly increased CP and CP/ATP in all myocardial layers, and the transmural gradient of CP/ATP was abolished again. These studies indicate that in present experimental model 1) myocardial performance is not constrained by inadequate perfusion in any myocardial layer although modest oxygen limitation affects the kinetics of oxidative phosphorylation in the inner myocardial layers and 2) in all myocardial layers, submaximal activation of intermediary metabolism and oxidative phosphorylation reactions results in lower steady-state CP and higher ADP levels relative to their respective values when energy expenditure is markedly reduced by KCl arrest.


2020 ◽  
Vol 14 (10) ◽  
pp. 2580-2594 ◽  
Author(s):  
William D. Orsi ◽  
Raphaël Morard ◽  
Aurele Vuillemin ◽  
Michael Eitel ◽  
Gert Wörheide ◽  
...  

Abstract Foraminifera are single-celled eukaryotes (protists) of large ecological importance, as well as environmental and paleoenvironmental indicators and biostratigraphic tools. In addition, they are capable of surviving in anoxic marine environments where they represent a major component of the benthic community. However, the cellular adaptations of Foraminifera to the anoxic environment remain poorly constrained. We sampled an oxic-anoxic transition zone in marine sediments from the Namibian shelf, where the genera Bolivina and Stainforthia dominated the Foraminifera community, and use metatranscriptomics to characterize Foraminifera metabolism across the different geochemical conditions. Relative Foraminifera gene expression in anoxic sediment increased an order of magnitude, which was confirmed in a 10-day incubation experiment where the development of anoxia coincided with a 20–40-fold increase in the relative abundance of Foraminifera protein encoding transcripts, attributed primarily to those involved in protein synthesis, intracellular protein trafficking, and modification of the cytoskeleton. This indicated that many Foraminifera were not only surviving but thriving, under the anoxic conditions. The anaerobic energy metabolism of these active Foraminifera was characterized by fermentation of sugars and amino acids, fumarate reduction, and potentially dissimilatory nitrate reduction. Moreover, the gene expression data indicate that under anoxia Foraminifera use the phosphogen creatine phosphate as an ATP store, allowing reserves of high-energy phosphate pool to be maintained for sudden demands of increased energy during anaerobic metabolism. This was co-expressed alongside genes involved in phagocytosis and clathrin-mediated endocytosis (CME). Foraminifera may use CME to utilize dissolved organic matter as a carbon and energy source, in addition to ingestion of prey cells via phagocytosis. These anaerobic metabolic mechanisms help to explain the ecological success of Foraminifera documented in the fossil record since the Cambrian period more than 500 million years ago.


1960 ◽  
Vol 198 (1) ◽  
pp. 213-216 ◽  
Author(s):  
Frederick E. Samson ◽  
William M. Balfour ◽  
Nancy A. Dahl

The rate of adenosinetriphosphate (ATP) disappearance in the brain after inhibition of aerobic and anaerobic metabolism was investigated. It was found that the rate increases with increasing age in the neonatal rat and that the effect of lowering the body temperature, which slows the rate, is greater in the 21-day rat than in the newborn. Calculation from the data gives 0.5 µm/sec/gm as the rate of high-energy phosphate utilization in the 21-day rat, and 0.04 µm/sec/gm in the 1-day rat. This increase in the rate of energy utilization during neonatal maturation is compared with the capacity to generate ATP; the utilization increase is found to be six times that of the capacity to generate ATP. The Q10 of the high-energy phosphate utilization in the 21-day rat is 1.7 in the 37°–25°C range, but is 10. in the 25°–15°C range. It is concluded that the rate of high-energy phosphate utilization is closely related to the amount of neuronal activity and, further, that the energy cost per average nerve impulse probably is greater in the adult brain than in the neonatal brain.


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