The distribution of calcium in hypoxic cat hearts: the effect of β1-blockade

1978 ◽  
Vol 56 (4) ◽  
pp. 564-570 ◽  
Author(s):  
Cathy C. Y. Pang ◽  
Leslie E. Bailey
Keyword(s):  
Contractile Activity ◽  
Blocking Agent ◽  
Contractile Force ◽  
Rapid Decrease ◽  
Coupling Mechanism ◽  
Hypoxic Conditions ◽  
Concomitant Reduction ◽  
Mammalian Myocardium ◽  
Residual Tissue

Contractile activity decays rapidly during the first few minutes of hypoxia in the mammalian myocardium. These changes may be the result of redistribution of the Ca involved in the excitation–contraction (E–C) coupling mechanism. It was the purpose of this study to determine if distortions in the Ca pool(s) involved in E–C coupling are responsible for the acute reduction in contractile force in the heart. Working, Langendorff kitten heart preparations were perfused with a Krebs–Henseleit solution equilibrated with 5% O2, 5% CO2, and 90% N2. Within 3 min of initiation of this treatment the Ca content of a pool directly involved in E–C coupling (Ca2) was reduced by approximately one-half, and this was accompanied by an equivalent increase in a slowly exchanging Ca pool (Ca3). A concomitant reduction in contractile force was associated with this redistribution of Ca. The Ca remaining in the heart after contractility had been abolished by Ca-free perfusion (residual tissue Ca) was significantly elevated by hypoxia. The β1 blocking agent practolol (10−5 M), prevented the hypoxia-induced reduction in Ca content of Ca2 produced by hypoxia, but had no effect on contractility under hypoxic conditions or during re-oxygenation. Practolol did not prevent the increase in residual tissue Ca induced by hypoxia. It was concluded that the immediate reduction in contractility caused by hypoxia was not causally related to the reduction in the quantity of Ca in Ca2, the pool involved in E–C coupling, but may be related to a rapid decrease in the supply of energy for contraction.

Ischemic preconditioning-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contraction-induced myocardial injury

2004 ◽  
Vol 287 (1) ◽  
pp. H81-H90 ◽  
Author(s):  
Masakuni Kido ◽  
Hajime Otani ◽  
Shiori Kyoi ◽  
Tomohiko Sumida ◽  
Hiroyoshi Fujiwara ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Myocardial Injury ◽  
Contractile Activity ◽  
Integral Membrane Protein ◽  
Contractile Force ◽  
Global Ischemia ◽  
Blue Dye ◽  
Perfused Heart ◽  
Complete Restoration ◽  
Rat Hearts

Dystrophin is an integral membrane protein involved in the stabilization of the sarcolemmal membrane in cardiac muscle. We hypothesized that the loss of membrane dystrophin during ischemia and reperfusion is responsible for contractile force-induced myocardial injury and that cardioprotection afforded by ischemic preconditioning (IPC) is related to the preservation of membrane dystrophin. Isolated and perfused rat hearts were subjected to 30 min of global ischemia, followed by reperfusion with or without the contractile blocker 2,3-butanedione monoxime (BDM). IPC was introduced by three cycles of 5-min ischemia and 5-min reperfusion before the global ischemia. Dystrophin was distributed exclusively in the membrane of myocytes in the normally perfused heart but was redistributed to the myofibril fraction after 30 min of ischemia and was lost from both of these compartments during reperfusion in the presence or absence of BDM. The loss of dystrophin preceded uptake of the membrane-impermeable Evans blue dye by myocytes that occurred after the withdrawal of BDM and was associated with creatine kinase release and the development of contracture. Although IPC did not alter the redistribution of membrane dystrophin induced by 30 min of ischemia, it facilitated the restoration of membrane dystrophin during reperfusion. Also, myocyte necrosis was not observed when BDM was withdrawn after complete restoration of membrane dystrophin. These results demonstrate that IPC-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contractile force-induced myocardial injury and suggest that the cardioprotection conferred by IPC can be enhanced by the temporary blockade of contractile activity until restoration of membrane dystrophin during reperfusion.

Cellular and molecular mechanisms of hypoxia-inducible factor driven vascular remodeling

2007 ◽  
Vol 97 (05) ◽  
pp. 774-787 ◽  
Author(s):  
Norbert Weissmann ◽  
Friedrich Grimminger ◽  
Werner Seeger ◽  
Frank Rose ◽  
Jörg Hänze
Keyword(s):  
Vascular Remodeling ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Genetic Manipulation ◽  
Hypoxia Inducible Factor ◽  
Ischemic Disease ◽  
Hypoxic Conditions ◽  
Concomitant Reduction ◽  
Adaptive Processes

SummaryHypoxia-inducible factor (HIF) is an oxygen-dependent transcription factor that activates a diverse set of target genes, the products of which are involved in adaptive processes to hypoxia. Employing genetic manipulation of HIF expression, in-vivo and cellular studies have focused on HIF as a crucial factor affecting hypoxia-induced vascular remodeling.Vascular remodeling comprises processes which establish and improve blood vessel supply such as vasculogenesis, angiogenesis and arteriogenesis. These processes are observed during ontogenesis, tumor progression, ischemic disease or physical training. Furthermore, under hypoxic conditions, a pulmonary-specific type of vascular remodeling called pulmonary arterial remodeling occurs that is characterized by thickening of the vessel wall with a concomitant reduction in the vessel lumen area, thereby limiting blood flow.This response results in pulmonary hypertension with right ventricular hypertrophy, a lethal disease. In this review, we summarize and discuss mechanisms by which HIF interferes with the different vascular remodeling processes.

scholarly journals Maximum activities and effects of fructose bisphosphate on pyruvate kinase from muscles of vertebrates and invertebrates in relation to the control of glycolysis

1978 ◽  
Vol 174 (3) ◽  
pp. 989-998 ◽  
Author(s):  
Victor A. Zammit ◽  
Isidorus Beis ◽  
Eric A. Newsholme
Keyword(s):  
Pyruvate Kinase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Contractile Activity ◽  
Mass Action ◽  
Glycolytic Flux ◽  
Fructose Bisphosphate ◽  
Efficient System ◽  
Hypoxic Conditions ◽  
Sufficient Energy ◽  
Ratio Data

1. Comparison of the maximum activities of pyruvate kinase with those of phosphofructokinase in a large number of muscles from invertebrates and vertebrates indicates that, in general, in any individual muscle, the activity of pyruvate kinase is only severalfold higher than that of phosphofructokinase. This is consistent with the suggestion, based on mass-action ratio data, that the pyruvate kinase reaction is non-equilibrium in muscle. However, the range of activities of pyruvate kinase in these muscles is considerably larger than that of phosphofructokinase. This difference almost disappears if the enzyme activities from muscles that are known to possess an anaerobic ‘succinate pathway’ are excluded. It is suggested that, in these muscles, phosphofructokinase provides glycolytic residues for both pyruvate kinase (i.e. glycolysis) and phosphoenolpyruvate carboxykinase (i.e. the succinate pathway). This is supported by a negative correlation between the activity ratio, pyruvate kinase/phosphofructokinase, and the activities of nucleoside diphosphokinase in these muscles, since high activities of nucleoside diphosphokinase are considered to indicate the presence of the succinate pathway. 2. The effect of fructose bisphosphate on the activities of pyruvate kinase from many different muscles was studied. The stimulatory effect of fructose bisphosphate appears to be lost whenever an efficient system for supply of oxygen to the muscles is developed (e.g. insects, squids, birds and mammals). This suggests that activation of pyruvate kinase is important in the co-ordinated regulation of glycolysis in anaerobic or hypoxic conditions, when the change in glycolytic flux during the transition from rest to activity needs to be large in order to provide sufficient energy for the contractile activity. However, lack of this effect in the anaerobic muscles of the birds and mammals suggests that another metabolic control may exist for avian and mammalian pyruvate kinase in these muscles.

Reversal of phosphorylase activation in muscle despite continued contractile activity

1979 ◽  
Vol 237 (5) ◽  
pp. R291-R296 ◽  
Author(s):  
R. K. Conlee ◽  
J. A. McLane ◽  
M. J. Rennie ◽  
W. W. Winder ◽  
J. O. Holloszy
Keyword(s):  
Steady State ◽  
Contractile Activity ◽  
Contractile Force ◽  
Significant Decline ◽  
Phosphorylase Activity ◽  
Contracting Muscle ◽  
Beta Form ◽  
Energy Needs ◽  
Complete Reversal ◽  
Glycogen Breakdown

During studies of the regulation of phosphorylase activity and glycogenolysis in contracting muscle, it was found that conversion of phosphorlyase beta to alpha is transient. Reversal of phosphorylase activation during both continuous and intermittent stimulation in the plantaris might, in part, have been due to development of fatigue. However, a complete reversal of phosphorylase activation was also evident within 5 min in the absence of fatigue in soleus muscles stimulated tetanically with 100-ms-long trains at a rate of 60/min. These muscles showed no significant decline in contractile force. Glycogen breakdown stopped in the soleus when phosphorylase reverted to the beta form, providing evidence that phosphorylase beta was not active. This lack of activity is probably explained by the finding that ATP and AMP concentrations changed little, while glucose 6-phosphate increased. Reversal of phosphorlyase activation soon after the onset of steady-state work may be a mechanism for conserving glycogen when the supply of other substrates is adequate to meet the muscles' energy needs.

Effect of Oxygen Free Radicals on Cardiac Contractile Activity and Sarcolemmal Na+–Ca2+ Exchange

1996 ◽  
Vol 1 (3) ◽  
pp. 211-217
Author(s):  
Taku Matsubara ◽  
Naranjan S. Dhalla
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Xanthine Oxidase ◽  
Cardiac Dysfunction ◽  
Oxygen Free Radicals ◽  
Contractile Activity ◽  
Contractile Force ◽  
Cardiac Contractile ◽  
Intracellular Ca ◽  
Exchange Activity

Background Although oxygen free radicals have been shown to induce myocardial cell damage and cardiac dysfunction, the exact mechanism by which these radicals affect the heart function is not clear. Since the occurrence of intracellular Ca2+ overload is critical in the genesis of cellular damage and cardiac dysfunction, and since the sarcolemmal Na+–Ca2+ exchange is intimately involved in Ca2+ movements in myocardium, this study was undertaken to examine the effects of oxygen free radicals on the relationship between changes in cardiac contractile force development and sarcolemmal Na+–Ca2+ exchange activity. Methods and Results Isolated rat hearts were perfused with a medium containing xanthine plus xanthine oxidase for different times, and changes in contractile force as well as sarcolemmal Na+–Ca2+ exchange activity were monitored. Perfusion of the heart with xanthine plus xanthine oxidase resulted in a transient increase followed by a marked decrease in contractile activity; the resting tension was markedly increased. The xanthine plus xanthine oxidase-induced depression in developed tension, rate of contraction, and rate of relaxation, except the transient increase in contractile activity, was prevented by the addition of catalase, but not by superoxide dismutase, in the perfusion medium. A time-dependent depression in sarcolemmal Na+–Ca2+ was also evident upon perfusing the heart with xanthine plus xanthine oxidase. This depression in Na+-dependent Ca2+ uptake was associated with a decrease in the maximal velocity of reaction without any changes in the affinity of Na+–Ca2+ exchanger for Ca2+. The presence of catalase, unlike superoxide dismutase, prevented the decrease in sarcolemmal Na+–Ca2+ exchange activity in hearts perfused with xanthine plus xanthine oxidase. Conclusion The results support the view that a depression in the sarcolemmal Na+–Ca2+ exchange activity may contribute to the occurrence of intracellular Ca2+ overload and subsequent decrease in contractile activity. Furthermore, these actions of xanthine plus xanthine oxidase in the whole heart appear to be a consequence of H2O2 production rather than the ‘ generation of superoxide radicals.

Calcium-linked changes in myocardial metabolism in the isolated perfused rat heart

1977 ◽  
Vol 55 (4) ◽  
pp. 925-933 ◽  
Author(s):  
N. S. Dhalla ◽  
J. C. Yates ◽  
V. Proveda
Keyword(s):  
Cyclic Amp ◽  
Myocardial Metabolism ◽  
Contractile Activity ◽  
Control Level ◽  
Creatine Phosphate ◽  
High Energy ◽  
Contractile Force ◽  
Increase Glucose Uptake ◽  
Rat Hearts ◽  
External Calcium

Rat hearts were perfused for 40 min with aerobic medium containing different concentrations of calcium (0–5 mM) and their abilities to take up and oxidize glucose, and to produce lactate and glycerol were examined in addition to measuring glycogen, lipids, cyclic AMP, and high energy phosphate stores. Increasing the concentration of calcium was found to decrease myocardial glycogen but increase glucose uptake, glucose oxidation, and lactate release. A decrease in myocardial triglycerides and an increase in free fatty acid contents as well as glycerol release without any changes in cholesterol and phospholipid contents were observed upon increasing the concentration of external calcium. In comparison with the hearts perfused with Ca2+-free medium, the levels of creatine phosphate and ATP were lower and that of ADP higher in hearts perfused with medium containing 5 mM calcium. No differences in AMP and cyclic AMP contents were seen among hearts perfused with different concentrations of calcium. The contractile activity initially increased upon increasing the concentration of calcium from 1.25 to 5 mM and then declined towards the control level. The hearts were unable to generate contractile force in the absence of calcium, whereas the contractile force decreased and then began to recover upon perfusing the hearts with 0.31 mM calcium. These results indicate that elevated levels of intracellular calcium stimulate glycogenolytic, glycolytic, and lipolytic processes in myocardium directly.

Modulation of gastric motor activity by a centrally acting stimulus, circular vection, in humans

2001 ◽  
Vol 280 (5) ◽  
pp. G850-G857 ◽  
Author(s):  
Henryk Faas ◽  
Christine Feinle ◽  
Paul Enck ◽  
David Grundy ◽  
Peter Boesiger
Keyword(s):  
Gastric Emptying ◽  
Healthy Subjects ◽  
Time Course ◽  
Delayed Gastric Emptying ◽  
Contractile Activity ◽  
Subjective Symptom ◽  
Gastric Volume ◽  
Rapid Decrease ◽  
Resonance Imaging ◽  
Baseline Activity

The aims of this study were to investigate gastric motor correlates of vection, a centrally acting stimulus, and relate these responses to the induction of motion sickness symptoms. Antral contractile activity and gastric volume retained after a liquid nutrient meal (600 ml) were assessed by magnetic resonance imaging in healthy subjects during two different protocols. Vection was induced by an optokinetic drum, and subjects repeatedly rated the intensity of vection and nausea on 0–10 analog scales. Vection delayed gastric emptying {99% (89–102%) [median (interquartile ranges)] of volume retained at 28 min; control situation: 79% (69–81%), P < 0.05}. Antral contractile activity followed a distinct time course of rapid decrease [−64% (−72 to −59%) change from baseline activity] immediately after onset of drum rotation followed by gradual recovery upon withdrawal of the stimulus. No relationship was found between the severity of nausea and inhibition of gastric emptying or antral contractile activity. The inhibition of antral contractile activity appears to be a good measure of the peripheral response to vection but is probably independent of subjective symptom induction.

Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog

1984 ◽  
Vol 247 (6) ◽  
pp. G688-G694 ◽  
Author(s):  
Z. Itoh ◽  
M. Nakaya ◽  
T. Suzuki ◽  
H. Arai ◽  
K. Wakabayashi
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Intravenous Infusion ◽  
Contractile Activity ◽  
Contractile Force ◽  
Naturally Occurring ◽  
Gastrointestinal Motor ◽  
Plasma Motilin ◽  
Interdigestive Migrating Contractions ◽  
Gastrointestinal Contractile Activity

The gastrointestinal motor stimulating activity of erythromycin (EM) was studied in conscious dogs. It was found that a 20-min intravenous infusion of EM lactobionate at a dose of 50–100 micrograms (potency) X kg-1 X h-1 induced a group of strong contractions in the stomach and the duodenum, and the contractions migrated along the small intestine to the terminal ileum. The EM-induced contractions were quite similar to the naturally occurring interdigestive migrating contractions (IMC) in the gastrointestinal tract in frequency, contractile force, and duration of the contractions, migrating velocity, and accompanying peaks of plasma motilin concentration. The EM-induced contractions in the stomach were inhibited by feeding and intravenous infusion of pentagastrin (1.5 micrograms X kg-1 X h-1) but were not affected by secretin; these findings are identical to those found with the naturally occurring and motilin-induced contractions. Like motilin, EM stimulated motor activity only during the interdigestive state. We conclude that EM induces IMC associated with the release of endogenous motilin in the dog.

Release of Intracellular Enzymes from An Isolated Mammalian Skeletal Muscle Preparation

1983 ◽  
Vol 65 (2) ◽  
pp. 193-201 ◽  
Author(s):  
D. A. Jones ◽  
M. J. Jackson ◽  
R. H. T. Edwards
Keyword(s):  
Skeletal Muscle ◽  
Contractile Activity ◽  
Atp Depletion ◽  
Mammalian Skeletal Muscle ◽  
Enzyme Release ◽  
Muscle Preparation ◽  
Muscle Enzymes ◽  
Hypoxic Conditions ◽  
Detergent Treatment

1. An isolated skeletal muscle preparation is described which has been used to study the efflux of enzymes in response to contractile activity, metabolic poisons and detergent treatment. 2. In both fast and slow muscles contractile activity caused a release of lactate dehydrogenase and creatine kinase that reached a peak 1–2 h after the end of stimulation. There was very little release during the 30 min stimulation period whether the muscles were under aerobic or hypoxic conditions. 3. Incubation of the muscles with cyanide and iodoacetate caused a similar delayed release of enzyme. 4. Disruption of cell membranes with detergent treatment caused an entirely different and very rapid pattern of enzyme release. 5. Enzyme release from the fatigued isolated muscle preparations appears to be initiated as a consequence of phosphorylcreatine or ATP depletion. The relevance of this to release of muscle enzymes after activity in vivo is discussed.

Sign in / Sign up

Export Citation Format

Share Document