Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm

2005 ◽  
Vol 98 (5) ◽  
pp. 1753-1760 ◽  
Author(s):  
V. P. Wright ◽  
P. F. Klawitter ◽  
D. F. Iscru ◽  
A. J. Merola ◽  
T. L. Clanton
Keyword(s):  
Contractile Function ◽  
Force Production ◽  
Creatine Phosphate ◽  
High Energy ◽  
Diaphragm Muscle ◽  
Severe Hypoxia ◽  
High Energy Phosphates ◽  
Rat Diaphragm ◽  
Tetanic Force ◽  
Hypoxia Exposure

Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of Pi. Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 μM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca2+ concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to ∼10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates.

High-energy phosphate compounds of rat diaphragm and skeletal muscle fibers

1961 ◽  
Vol 200 (1) ◽  
pp. 182-186 ◽  
Author(s):  
Ruth D. Peterson ◽  
Clarissa H. Beatty ◽  
Rose M. Bocek
Keyword(s):  
Uric Acid ◽  
Absorption Maximum ◽  
Room Temperature ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates ◽  
Rat Diaphragm ◽  
High Energy Phosphate ◽  
Atp Levels

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.

Influence of intracellular acidosis on contractile function in the working rat heart

1987 ◽  
Vol 253 (6) ◽  
pp. H1499-H1505 ◽  
Author(s):  
F. M. Jeffrey ◽  
C. R. Malloy ◽  
G. K. Radda
Keyword(s):  
Stroke Volume ◽  
Intracellular Ph ◽  
Rat Heart ◽  
Contractile Function ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Intracellular Acidosis ◽  
Tension Development ◽  
O2 Delivery

The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. We developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O2 delivery. Intracellular pH and high-energy phosphates were monitored by 31P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH4Cl (extracellular pH, 7.4). The subsequent washout of NH3 from the cytosol generated a slight acidosis (from intracellular pH 7.0 to 6.8) which was associated with little change in the determinants of O2 consumption (rate-pressure product) and O2 delivery (coronary flow). Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. Results were qualitatively similar at different external [Ca2+] (1.75, 2.5, 3.15 mM) and preload (12 or 21 cmH2O) but were most prominent at the lowest external [Ca2+] and left atrial pressure. In contrast to this model of isolated intracellular acidosis, hearts subject to a respiratory (extracellular plus intracellular) acidosis showed a marked reduction in pressure development. It was concluded that 1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and 2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.

Effect of hypoxia on myocardial high-energy phosphates in the neonatal mammalian heart

1978 ◽  
Vol 235 (5) ◽  
pp. H475-H481 ◽  
Author(s):  
J. M. Jarmakani ◽  
T. Nagatomo ◽  
M. Nakazawa ◽  
G. A. Langer
Keyword(s):  
Lactate Production ◽  
Creatine Phosphate ◽  
High Energy ◽  
Adult Rabbit ◽  
High Energy Phosphates ◽  
Mechanical Function ◽  
High Energy Phosphate ◽  
Buffer Solution ◽  
Bicarbonate Buffer ◽  
Atp Concentration

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.

scholarly journals Reductions in mitochondrial O2 consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium

2009 ◽  
Vol 297 (1) ◽  
pp. H223-H232 ◽  
Author(s):  
Qingsong Hu ◽  
Gen Suzuki ◽  
Rebeccah F. Young ◽  
Brian J. Page ◽  
James A. Fallavollita ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
High Energy ◽  
Atp Depletion ◽  
Hibernating Myocardium ◽  
Wall Thickening ◽  
High Energy Phosphates ◽  
Simulated Ischemia

We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating left anterior descending coronary regions (systolic wall thickening = 2.8 ± 0.2 vs. 5.4 ± 0.3 mm in remote myocardium), and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37°C). At baseline, ATP (20.1 ± 1.0 vs. 26.7 ± 2.1 μmol/g dry wt, P < 0.05), ADP (8.1 ± 0.4 vs. 10.3 ± 0.8 μmol/g, P < 0.05), and total adenine nucleotides (31.2 ± 1.3 vs. 40.1 ± 2.9 μmol/g, P < 0.05) were depressed compared with normal myocardium, whereas total creatine, creatine phosphate, and ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6 ± 0.9 vs. 13.7 ± 1.7 μmol/g at 20 min in control, P < 0.05) and mitochondrial respiration [145 ± 13 vs. 187 ± 11 ng atoms O2·mg protein−1·min−1 in control (state 3), P < 0.05], whereas lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium is ischemia tolerant, with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia, which may maintain myocyte viability.

Contractile and metabolic effects of increased creatine kinase activity in mouse skeletal muscle

1996 ◽  
Vol 270 (4) ◽  
pp. C1236-C1245 ◽  
Author(s):  
B. B. Roman ◽  
J. M. Foley ◽  
R. A. Meyer ◽  
A. P. Koretsky
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Kinase Activity ◽  
Contractile Function ◽  
Contractile Activity ◽  
High Energy ◽  
Metabolic Effects ◽  
High Energy Phosphates ◽  
Lactate Dehydrogenase Activity ◽  
B Subunit

The effects of increased expression of creatine kinase (CK) in skeletal muscle were studied in control and transgenic animals homozygous for expression of the B subunit of CK. CK activity was 47% higher in transgenic gastrocnemius muscle. The CK activity was distributed as follows: 45 +/- 1% MM dinner, 31 +/- 4% MB dimer, and 22 +/- 5% BB dimer. No significant differences in metabolic or contractile proteins were detected except for a 22% decrease in lactate dehydrogenase activity and a 9% decrease in adenylate kinase activity. The only significant effect in contractile activity was that the rise time of a 5-s isometric contraction was 28% faster in the transgenic muscle. 31P nuclear magnetic resonance (NMR) spectra were obtained from control and transgenic muscles during mechanical activation, and there were no NMR measurable differences detected. These results indicate that a 50% increase in CK activity due to expression of the B subunit does not have large effects on skeletal muscle metabolism or contractile function. Therefore, control muscle has sufficient CK activity to keep up with changes in cellular high-energy phosphates except during the early phase of intense contractile activity.

Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat

2009 ◽  
Vol 333 (1-2) ◽  
pp. 269-277 ◽  
Author(s):  
Stefano Signoretti ◽  
Valentina Di Pietro ◽  
Roberto Vagnozzi ◽  
Giuseppe Lazzarino ◽  
Angela M. Amorini ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates

Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability

2003 ◽  
Vol 284 (4) ◽  
pp. H1313-H1320 ◽  
Author(s):  
Yong-Mei Cha ◽  
Petras P. Dzeja ◽  
Win K. Shen ◽  
Arshad Jahangir ◽  
Chari Y. T. Hart ◽  
...  
Keyword(s):  
Chronic Atrial Fibrillation ◽  
Creatine Phosphate ◽  
Ventricular Myocardium ◽  
High Energy ◽  
Oxidative Modification ◽  
Potential Contribution ◽  
High Energy Phosphates ◽  
Atrial Myocardium ◽  
Electrical Instability ◽  
Atrial Area

The failing ventricular myocardium is characterized by reduction of high-energy phosphates and reduced activity of the phosphotransfer enzymes creatine kinase (CK) and adenylate kinase (AK), which are responsible for transfer of high-energy phosphoryls from sites of production to sites of utilization, thereby compromising excitation-contraction coupling. In humans with chronic atrial fibrillation (AF) unassociated with congestive heart failure (CHF), impairment of atrial myofibrillar energetics linked to oxidative modification of myofibrillar CK has been observed. However, the bioenergetic status of the failing atrial myocardium and its potential contribution to atrial electrical instability in CHF have not been determined. Dogs with ( n = 6) and without ( n = 6) rapid pacing-induced CHF underwent echocardiography (conscious) and electrophysiological (under anesthesia) studies. CHF dogs had more pronounced mitral regurgitation, higher atrial pressure, larger atrial area, and increased atrial fibrosis. An enhanced propensity to sustain AF was observed in CHF, despite significant increases in atrial effective refractory period and wavelength. Profound deficits in atrial bioenergetics were present with reduced activities of the phosphotransfer enzymes CK and AK, depletion of high-energy phosphates (ATP and creatine phosphate), and reduction of cellular energetic potential (ATP-to-ADP and creatine phosphate-to-Cr ratios). AF duration correlated with left atrial area ( r = 0.73, P = 0.01) and inversely with atrial ATP concentration ( r = −0.75, P = 0.005), CK activity ( r = −0.57, P = 0.054), and AK activity ( r = −0.64, P = 0.02). Atrial levels of malondialdehyde, a marker of oxidative stress, were significantly increased in CHF. Myocardial bioenergetic deficits are a conserved feature of dysfunctional atrial and ventricular myocardium in CHF and may constitute a component of the substrate for AF in CHF.

Exercise hyperthermia as a factor limiting physical performance: temperature effect on muscle metabolism

1985 ◽  
Vol 59 (3) ◽  
pp. 766-773 ◽  
Author(s):  
S. Kozlowski ◽  
Z. Brzezinska ◽  
B. Kruk ◽  
H. Kaciuba-Uscilko ◽  
J. E. Greenleaf ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Muscle Metabolism ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates ◽  
Glycogen Depletion ◽  
Heavy Exercise ◽  
High Energy Phosphate ◽  
Glycolytic Intermediates ◽  
Temperature Equilibrium

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.

Metabolic responses to varying restrictions of coronary blood flow in swine

1975 ◽  
Vol 228 (2) ◽  
pp. 655-662 ◽  
Author(s):  
AJ Liedtke ◽  
HC Hughes ◽  
Neely
Keyword(s):  
Fatty Acid ◽  
Coronary Flow ◽  
Mechanical Performance ◽  
Glucose Consumption ◽  
Creatine Phosphate ◽  
High Energy ◽  
Coronary Perfusion ◽  
Acid Extraction ◽  
High Energy Phosphates ◽  
Tissue Levels

An in situ working swine heart preparation is described in which total coronary perfusion was controlled. At normal rates of coronary flow, oxygen, glucose, and fatty acid utilization were stable for at least a 60-min perfusion period. With a 50% reduction in coronary flow, oxygen and glucose consumption were reduced during 30 min of perfusion and fatty acid extraction was lower at the end of 30 min. Glycogen utilization was increased, but tissue levels of creatine phosphate, ATP, and lactate were similar to those in hearts receiving normal flow. With a 60% reduction in coronary flow, uptake of oxygen, glucose, and fatty acids were further decreased. Tissue levels of high-energy phosphates and glycogen were decreased and ADP, AMP, and lactate increased. Mechanical performance progressively deteriorated in these hearts, and ventricular fibrillation developed after about 20 min (19.8 plus or minus 3.0 min). The data indicate that this preparation is suitable for the study of myocardial metabolism during mild and severe ischemia and may be useful for the evaluation of pharmacological interventions designed for the treatment of myocardial ischemia.

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