Energy metabolism and adenine nucleotide degradation in twitch-stimulated rat hindlimb during ischemia-reperfusion

1993 ◽  
Vol 264 (4) ◽  
pp. E655-E661 ◽  
Author(s):  
D. G. Welsh ◽  
M. I. Lindinger
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Control Period ◽  
High Energy ◽  
Nucleotide Degradation

The purpose of this study was to characterize twitch tension and energy metabolism in ischemic, stimulated rat hindlimb to determine its suitability as a rapid time course model of ischemia-reperfusion injury. After 15 min equilibration, rat hindlimbs were stimulated (1-Hz twitches, 0.2 ms pulse duration, 15 V) for 5 min (control, n = 8). This twitch protocol was maintained throughout the ischemic and reperfusion periods. The control period was followed by 5, 20, or 40 min of ischemia (ligation of femoral artery and vein) or 40 min of ischemia with 0, 5, or 20 min of reperfusion (removal of ligature). The soleus [89% slow oxidative (SO)] and the white gastrocnemius [WG; 91% fast glycolytic (FG)] were analyzed for phosphocreatine (PCr), adenine nucleotides, glycogen, and glycolytic intermediates. Ischemia was characterized by progressive decreases in twitch tension, high-energy phosphagens, total adenine nucleotides (TAN), and glycogen. Also, energy metabolism was altered at a greater rate in WG than in soleus. Reperfusion resulted in a recovery in PCr and lactate, with little change in ATP, TAN, or glycogen. The inability to resynthesize adenine nucleotides and glycogen during reperfusion is characteristic of damaged skeletal muscle. The extent of the metabolic alterations in SO and FG muscles during twitch stimulation was comparable with previously reported noncontracting ischemia protocols of 2-4 and 4-7 h in length, respectively. The present study demonstrates that twitch stimulation of ischemic skeletal muscle is a useful model for inducing rapid metabolic changes and an ischemic insult comparable to prolonged noncontracting ischemia-reperfusion models.

When does the lung die?K fc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung

1997 ◽  
Vol 83 (1) ◽  
pp. 247-252 ◽  
Author(s):  
David R. Jones ◽  
Randy M. Becker ◽  
Steve C. Hoffmann ◽  
John J. Lemasters ◽  
Thomas M. Egan
Keyword(s):  
Cell Viability ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Rat Lung ◽  
Donor Pool ◽  
Ischemic Time

Jones, David R., Randy M. Becker, Steve C. Hoffmann, John J. Lemasters, and Thomas M. Egan. When does the lung die? K fc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung. J. Appl. Physiol. 83(1): 247–252, 1997.—Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient ( K fc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. K fc increased with increasing postmortem ischemic time ( r = 0.88). Lungs ventilated with O2 1 h postmortem had similar K fc and wet-to-dry ratios as controls. Nonventilated lungs had threefold ( P < 0.05) and sevenfold ( P < 0.0001) increases in K fc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing K fc values ( r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal K fc with preharvest O2 ventilation. The relationship between K fc and TAN suggests that vascular permeability may be related to lung TAN levels.

scholarly journals Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

2019 ◽  
Vol 21 (1) ◽  
pp. 88 ◽  
Author(s):  
Spencer G. Miller ◽  
Paul S. Hafen ◽  
Jeffrey J. Brault
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Intracellular Signaling ◽  
Adenine Nucleotide ◽  
Degradation Products ◽  
Adenine Nucleotides ◽  
Skeletal Muscle Atrophy ◽  
Valuable Insight ◽  
Disease States ◽  
Nucleotide Degradation

Adenine nucleotides (AdNs: ATP, ADP, AMP) are essential biological compounds that facilitate many necessary cellular processes by providing chemical energy, mediating intracellular signaling, and regulating protein metabolism and solubilization. A dramatic reduction in total AdNs is observed in atrophic skeletal muscle across numerous disease states and conditions, such as cancer, diabetes, chronic kidney disease, heart failure, COPD, sepsis, muscular dystrophy, denervation, disuse, and sarcopenia. The reduced AdNs in atrophic skeletal muscle are accompanied by increased expression/activities of AdN degrading enzymes and the accumulation of degradation products (IMP, hypoxanthine, xanthine, uric acid), suggesting that the lower AdN content is largely the result of increased nucleotide degradation. Furthermore, this characteristic decrease of AdNs suggests that increased nucleotide degradation contributes to the general pathophysiology of skeletal muscle atrophy. In view of the numerous energetic, and non-energetic, roles of AdNs in skeletal muscle, investigations into the physiological consequences of AdN degradation may provide valuable insight into the mechanisms of muscle atrophy.

Prolonged adenine nucleotide resynthesis and reperfusion injury in postischemic skeletal muscle

1992 ◽  
Vol 262 (5) ◽  
pp. H1538-H1547 ◽  
Author(s):  
B. B. Rubin ◽  
S. Liauw ◽  
J. Tittley ◽  
A. D. Romaschin ◽  
P. M. Walker
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Time Course ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Prolonged Release ◽  
Intracellular Acidosis ◽  
Edema Formation ◽  
Muscle Necrosis

Skeletal muscle ischemia results in energy depletion and intracellular acidosis. Reperfusion is associated with impaired adenine nucleotide resynthesis, edema formation, and myocyte necrosis. The purpose of these studies was to define the time course of cellular injury and adenine nucleotide depletion and resynthesis in postischemic skeletal muscle during prolonged reperfusion in vivo. The isolated canine gracilis muscle model was used. After 5 h of ischemia, muscles were reperfused for either 1 or 48 h. Lactate and creatine phosphokinase (CPK) release during reperfusion was calculated from arteriovenous differences and blood flow. Adenine nucleotides, nucleosides, bases, and creatine phosphate were quantified by high-performance liquid chromatography, and muscle necrosis was assessed by nitroblue tetrazolium staining. Reperfusion resulted in a rapid release of lactate, which paralleled the increase in blood flow, and a delayed but prolonged release of CPK. Edema formation and muscle necrosis increased between 1 and 48 h of reperfusion (P less than 0.05). Recovery of energy stores during reperfusion was related to the extent of postischemic necrosis, which correlated with the extent of nucleotide dephosphorylation during ischemia (r = 0.88, P less than 0.001). These results suggest that both adenine nucleotide resynthesis and myocyte necrosis, which are protracted processes in reperfusing skeletal muscle, are related to the extent of nucleotide dephosphorylation during ischemia.

L-type Ca2+ channel and Na+/Ca2+ exchange inhibitors reduce Ca2+ accumulation in reperfused skeletal muscle

1996 ◽  
Vol 80 (4) ◽  
pp. 1263-1269 ◽  
Author(s):  
D. G. Welsh ◽  
M. I. Lindinger
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Blood Cells ◽  
Contractile Function ◽  
Adenine Nucleotides ◽  
High Energy ◽  
Ischemia And Reperfusion ◽  
Tension Recovery ◽  
Contractile Recovery ◽  
White Gastrocnemius

It is known that extracellular Ca2+ accumulates within skeletal muscle after prolonged periods of ischemia and reperfusion. In this study, we determined whether the L-type Ca2+ channel and the Na+/Ca2+ exchanger mediated Ca2+ influx and whether Ca2+ accumulation limited the metabolic and contractile recovery of reperfused skeletal muscle. Contracting rat hindlimbs (1-Hz twitch) exposed to 40 min of no-flow ischemia were reperfused with diltiazem (500 microM) or 3,4-dichlorobenzamil (300 microM) to block the Na+/Ca2+ exchanger and/or the L-type Ca2+ channel. High inhibitor concentrations were used to counter the binding of diltiazem and 3,4-dichlorobenzamil to albumin and red blood cells. Muscle Ca2+ accumulation, contractile function, and energy metabolism were assessed by measuring intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, twitch tension, and high-energy phosphagens [ATP, total adenine nucleotides (TAN) and phosphocreatine (PCr)]. Compared with control reperfusion, diltiazem and 3,4-dichlorobenzamil reduced Ca2+ influx and attenuated the rise in [Ca2+]i in the fast-oxidative glycolytic plantaris (Pl) and the fast-glycolytic white gastrocnemius (WG). The inhibitor-induced decrease in Ca2+ influx was 1.5- to 2-fold greater with 3,4-dichlorobenzamil than with diltiazem. Coinciding with the reduced Ca2+ accumulation, diltiazem and 3,4-dichlorobenzamil enhanced the resynthesis of ATP (Pl and WG), PCr (Pl and WG), and TAN (Pl) compared with control reperfusion. 3,4-Dichlorobenzamil also augmented twitch-tension recovery. We conclude that Ca2+ accumulation during reperfusion 1) arises from L-type Ca2+ channel and Na+/Ca2+ exchange activation; and 2) impairs the metabolic and contractile recovery of skeletal muscle.

Hepatic preconditioning preserves energy metabolism during sustained ischemia

2000 ◽  
Vol 279 (1) ◽  
pp. G163-G171 ◽  
Author(s):  
C. Peralta ◽  
R. Bartrons ◽  
L. Riera ◽  
A. Manzano ◽  
C. Xaus ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
High Energy ◽  
Energetic Cost ◽  
Main Role ◽  
Adenylate Energy Charge ◽  
Glycogen Depletion ◽  
Adenine Nucleotide Pool

We evaluated the possibility that ischemic preconditioning could modify hepatic energy metabolism during ischemia. Accordingly, high-energy nucleotides and their degradation products, glycogen and glycolytic intermediates and regulatory metabolites, were compared between preconditioned and nonpreconditioned livers. Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and adenylate energy charge; the accumulation of adenine nucleosides and bases was much lower in preconditioned livers, thus reflecting slower adenine nucleotide degradation. These effects were associated with a decrease in glycogen depletion and reduced accumulation of hexose 6-phosphates and lactate. 6-Phosphofructo-2-kinase decreased in both groups, reducing the availability of fructose-2,6-bisphosphate. Preconditioning sustained metabolite concentration at higher levels although this was not correlated with an increased glycolytic rate, suggesting that adenine nucleotides and cAMP may play the main role in the modulation of glycolytic pathway. Preconditioning attenuated the rise in cAMP and limited the accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen depletion. Our results suggest the induction of metabolic arrest and/or associated metabolic downregulation as energetic cost-saving mechanisms that could be induced by preconditioning.

Protective effects of glycine during hypothermic renal ischemia-reperfusion injury

1991 ◽  
Vol 261 (5) ◽  
pp. F841-F848 ◽  
Author(s):  
M. J. Mangino ◽  
M. K. Murphy ◽  
G. G. Grabau ◽  
C. B. Anderson
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Renal Ischemia ◽  
Cold Ischemia ◽  
Urine Production

The objective of this investigation was to test the effects of glycine, a cytoprotectant in normothermic in vitro models of renal ischemia, in a model of hypothermic renal preservation injury. This study also probes possible physiological mechanisms of glycine protection during renal hypothermic ischemia-reperfusion injury. Canine kidneys were subjected to 48 h of hypothermic ischemia (4 degrees C) after intravascular flush with cold conventional Collins solution (G. H. Collins, M. B. Bravo-Shugarman, and P. I. Terasaki, Lancet 2: 1219-1223, 1969) and were subsequently revascularized for 1 h. After 1 h of reperfusion, glomerular filtration rate, urine production, and electrolyte excretion were dramatically higher when the Collins flush contained 5 mM glycine, compared with the 0 mM glycine controls. Renal tissue adenine nucleotides and glutathione levels progressively declined with graded cold ischemia times, and glycine had no effect on these levels. However, renal tissue ATP levels (but not glutathione) were significantly higher when kidneys were flushed with glycine, stored for 48 h, and reoxygenated in vitro for 1 h at 37 degrees C, compared with kidneys flushed without glycine. Analysis of CoA esters from ischemic renal tissue indicated altered production of only butyryl CoA after 48 and 72 h of cold ischemia, but no differences were detected in glycine or control kidneys. In conclusion, this study reports dramatic functional preservation with glycine in kidneys subjected to hypothermic ischemia and in vivo reperfusion. The mechanisms of these effects appear not to be attributable to the maintenance of cellular adenine nucleotide or glutathione levels nor to the scavenging of accumulated amphipathic acyl CoA esters.

Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin

2006 ◽  
Vol 290 (3) ◽  
pp. C719-C727 ◽  
Author(s):  
Frank C. Chen ◽  
Ozgur Ogut
Keyword(s):  
Reperfusion Injury ◽  
Posttranslational Modifications ◽  
Actin Polymerization ◽  
Time Course ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Concentration ◽  
Cross Sectional ◽  
The Impact

The severity and duration of ischemia-reperfusion injury is hypothesized to play an important role in the ability of the heart subsequently to recover contractility. Permeabilized trabeculae were prepared from a rat model of ischemia-reperfusion injury to examine the impact on force generation. Compared with the control perfused condition, the maximum force (Fmax) per cross-sectional area and the rate of tension redevelopment of Ca2+-activated trabeculae fell by 71% and 44%, respectively, during ischemia despite the availability of a high concentration of ATP. The reduction in Fmax with ischemia was accompanied by a decline in fiber stiffness, implying a drop in the absolute number of attached cross bridges. However, the declines during ischemia were largely recovered after reperfusion, leading to the hypothesis that intrinsic, reversible posttranslational modifications to proteins of the contractile filaments occur during ischemia-reperfusion injury. Examination of thin-filament proteins from ischemic or ischemia-reperfused hearts did not reveal proteolysis of troponin I or T. However, actin was found to be glutathionylated with ischemia. Light-scattering experiments demonstrated that glutathionylated G-actin did not polymerize as efficiently as native G-actin. Although tropomyosin accelerated the time course of native and glutathionylated G-actin polymerization, the polymerization of glutathionylated G-actin still lagged native G-actin at all concentrations of tropomyosin tested. Furthermore, cosedimentation experiments demonstrated that tropomyosin bound glutathionylated F-actin with significantly reduced cooperativity. Therefore, glutathionylated actin may be a novel contributor to the diverse set of posttranslational modifications that define the function of the contractile filaments during ischemia-reperfusion injury.

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