UMLS:C0022116 - FACTA Search

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen free radicals have been implicated as mediators of cellular injury in ischemia-reperfusion. Since intracellular Ca(2+)-overload has been considered to play a crucial role in ischemia-reperfusion injury, this study was undertaken to examine the effects of oxygen free radicals on Ca(2+)-stimulated Mg(2+)-dependent ATPase activities and ATP-dependent Ca2+ accumulation in rat cardiac sarcolemmal membranes in vitro. Isolated rat heart sarcolemmal membranes were incubated with xanthine (X) + xanthine oxidase (XO) and assayed for Ca(2+)-pump activities. X + XO inhibited the Ca(2+)-pump activities in a time-dependent manner; a significant inhibition of Ca(2+)-stimulated ATPase activity was seen after one min of incubation. Superoxide dismutase showed a protective effect on depression in Ca(2+)-pump activities due to X + XO. To understand the involvement of sulfhydryl groups changes in causing depression of Ca(2+)-pump activities, the effects of oxygen free radicals on heart sarcolemmal sulfhydryl groups were also investigated. Heart sarcolemmal sulfhydryl groups were decreased by X + XO in a time-dependent manner. Superoxide dismutase showed a protective effect on sulfhydryl group depression caused by X + XO. N-ethylmaleimide, a sulfhydryl reagent, showed inhibitory effect on Ca(2+)-pump activities both in a time-, and a dose-dependent manner; dithiothreitol and cysteine prevented changes in Ca(2+)-pump activities caused by N-ethylmaleimide. The inhibitory effect of X + XO on Ca(2+)-pump activities were also prevented by the addition of dithiothreitol or cysteine. A significant correlation between changes in sarcolemmal Ca(2+)-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of heart sarcolemmal Ca(2+)-pump activity by oxygen free radicals. 202 66

The effect of ouabain on exocytotic and nonexocytotic norepinephrine release was investigated in perfused rat and guinea pig hearts. The overflow of endogenous norepinephrine and its neuronal metabolite 3,4-dihydroxyphenylethyleneglycol (DOPEG) was determined by high-pressure liquid chromatography. DOPEG served as the indicator of free axoplasmic norepinephrine concentrations. The overflow of the norepinephrine cotransmitter neuropeptide Y (NPY) was determined by radioimmunoassay and NPY was used as marker for exocytotic release. Electrical stimulation of the left stellate ganglion resulted in exocytotic norepinephrine release in rat and guinea pig hearts. Ouabain caused an increase in stimulation-induced norepinephrine overflow from rat and guinea pig hearts by 40%. However, overflow of NPY was decreased by 40%, indicating a reduced exocytosis rate. Ouabain increased both norepinephrine and NPY overflow, suggesting enhancement of exocytosis, when neuronal catecholamine uptake (uptake1) was blocked by desipramine or when presynaptic alpha 2-adrenoceptors were inhibited by yohimbine. The results demonstrate an interaction of ouabain with both calcium-dependent exocytosis and uptake1 of norepinephrine. Under calcium-free conditions, ouabain or potassium-free perfusate resulted in norepinephrine release from hearts when the axoplasmic norepinephrine concentration was elevated by the reserpinelike agent Ro 4-1284. This release was independent from neural activity, not accompanied by NPY overflow, and suppressed by the uptake1 blocker desipramine. These findings are in keeping with carrier-mediated nonexocytotic norepinephrine release that is caused by reversal of the transport direction of the uptake1 carrier. During myocardial ischemia nonexocytotic norepinephrine release was accelerated and enhanced by inhibition of Na+,K(+)-ATPase before ischemia. This study demonstrates the potential of digitalis glycosides to interact both with transmitter exocytosis and with the neuronal catecholamine transport system by Na+,K(+)-ATPase inhibition. Interaction with the catecholamine transport system involves both inhibition of norepinephrine inward transport and induction of norepinephrine outward transport, resulting in nonexocytotic norepinephrine release.
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PMID:Effect of digitalis glycosides on norepinephrine release in the heart. Dual mechanism of action. 203 16

Concurrent 23Na and 31P nuclear magnetic resonance spectroscopy has been employed to study the effects of ischemia upon the high-energy phosphagens and sodium ion concentration within the in vivo rat liver. High-energy phosphates in the form of ATP were depleted within 10 min of the onset of ischemia when measured by NMR. However, similar liver samples subjected to analytical biochemistry retained 27 +/- 12% of their ATP after a similar 10-min ischemic insult. Time-dependent 23Na NMR measurements, obtained in the presence of the shift reagent Dy(TTHA) to distinguish intracellular from extracellular sodium, revealed a rapid rise in the intracellular sodium when the liver was made ischemic. Intracellular and extracellular sodium concentrations approached equilibrium with an exponential time constant of 14.7 +/- 7 min. The initial rate of sodium influx was calculated to be 1.50 meq.l-1.min-1. The results indicate that the ischemic liver has a high passive sodium permeability and that NMR detectable 31P signals reflect the actual availability of cytosolic high-energy phosphates to enzymes, in this instance the membrane-bound [Na+, K+]-ATPase.
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PMID:Sodium flux and bioenergetics in the ischemic rat liver. 204 16

The development of muscle fatigue due to exhaustive exercise is associated with impaired sarcoplasmic reticulum (SR) Ca-transport activity. This study tested the hypothesis that SR failure is a consistent feature of cardiac and skeletal muscle fatigue owing to relative functional overload regardless of the method of induction: excessive stimulation, diminished performance capacity, or excessive excitation-contraction coupling. The Ca-transport activity was determined using three unique models of muscle fatigue: chronic and rapid ventricular pacing in dogs; metabolic inhibition caused by global cardiac ischemia in swine; and the hypermetabolic syndrome of porcine malignant hyperthermia (MH). Both pacing- and ischemia-induced fatigue resulted in reduction of SR Ca-transport ATPase activity: from 275 +/- 58 to 159 +/- 57 nmol.min-1.mg-1 (mU/mg) and from 577 +/- 82 to 177 +/- 133 mU/mg, respectively. Both pacing-induced fatigue and halothane-induced MH resulted in reduction of Ca-sequestration activity of muscle homogenates from 5.95 +/- 2.4 to 3.11 +/- 0.67 nM/s at 300 nM Ca and 38.7 +/- 10.5 to 16.3 +/- 8.0 nM/s at 1500 nM Ca, respectively (all p less than 0.01). The isolated SR Ca-ATPase activity correlated with Ca-sequestration activity of myocardial homogenates (r = 0.76; p less than 0.005). Different models were used to study the relationship of Ca-transport activity with relaxation function, degree of acidosis, and ionized Ca concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac and muscle fatigue due to relative functional overload induced by excessive stimulation, hypersensitive excitation-contraction coupling, or diminished performance capacity correlates with sarcoplasmic reticulum failure. 205 42

Changes of brain mitochondrial phospholipids during cerebral ischemia and recirculation were experimentally studied in a rat 4-vessel occlusion model, to explore the relation between changes of mitochondrial phospholipids and dysfunction of mitochondria. Respiratory functions, activities of respiratory enzymes (cytochrome c oxidase, F0F1-ATPase) were analyzed after 30 and 60 minutes of ischemia, and after 30 minutes of recirculation following each ischemic period. Activities of respiratory functions and respiratory enzymes decreased progressively during ischemia, which recovered completely after recirculation following 30 minutes of ischemia, while only partial recovery was observed after recirculation following 60 minutes of ischemia. In phospholipid analyses, contents of phospholipid classes tended to decrease time-dependently during ischemia, and compositions of polyunsaturated fatty acids (PUFA) such as arachidonic acid (20:4) and docosahexaenoic acid (22:6) were decreased preferentially. In recirculation, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) showed recovery of contents of phospholipids and compositions of PUFA after recirculation following 30 minutes of ischemia, while further decrease of contents of phospholipids and compositions of PUFA were observed after recirculation following 60 minutes of ischemia, especially in CL. On the other hand, progressive degradation of phospholipids occurred after recirculation following both 30 and 60 minutes of ischemia in phosphatidylserine and phosphatidylinositol. Changes of major phospholipid classes such as PC, PE, and CL correlated with the changes of mitochondrial respiratory functions and activities of respiratory enzymes. In conclusion, changes of mitochondrial membrane phospholipids appear to affect the integrity of cellular energy metabolism via mitochondrial dysfunction during cerebral ischemia and recirculation.
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PMID:[Experimental studies on the changes of mitochondrial membrane phospholipids during cerebral ischemia and recirculation]. 213 Jul 66

In the present study we examined the regulation of the cardiac muscle mitochondrial ATPase both in situ and in vitro in intact and sonicated mitochondria from rabbit, pigeon, and rat. We chose to study these three species because each is representative of one of the three classes into which all species thus far studied may be placed with respect to the in situ activity of their cardiac muscle mitochondrial ATPase inhibitor and with respect to the amount of ATPase inhibitor present in their cardiac muscle mitochondria (1). Class A species (rabbit) contain a full complement of ATPase inhibitor and show a marked ATPase inhibition during ischemia. Class B species (pigeon) also contain a full complement of inhibitor but exhibit only a low level of ATPase inhibition in situ. Class C species (rat) contain only low levels of inhibitor and, like class B species, don't appear to utilize the inhibitor they possess during ischemia in situ. We found that, while hearts from all three species developed a marked cytosolic acidosis during ischemia, only rabbit exhibited a marked ATPase inhibition in situ. In in vitro experiments in which matrix pH values close to 6.2 and delta psi values close to zero were measured in intact mitochondria from all three species, matrix pH appeared to be an important factor regulating ATPase inhibition in rabbit, but it had little effect upon ATPase--inhibitor interaction in pigeon and rat despite the lack of membrane potential. However, a pH-dependent further release of ATPase inhibitor was observed in sonicated pigeon heart mitochondria only. This latter observation suggests that, while slow heart-rate heart mitochondria appear to be designed for ATPase down regulation during ischemia by inhibitor binding to the ATPase, fast heart-rate heart mitochondria appear to be designed primarily for ATPase up regulation by a further release of inhibitor from the enzyme.
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PMID:Regulation of the mitochondrial adenosine 5'-triphosphatase in situ during ischemia and in vitro in intact and sonicated mitochondria from slow and fast heart-rate hearts. 214 Dec 43

Cardiac contractile activity is usually controlled by intracellular Ca2+, but it can also be modified by oxidizing agents. Incubation of guinea pig heart myofibrils with diamide (3 mM, 1 h) increased basal (no Ca2+) ATPase activity by 580% and abolished Ca2+ dependence. The effect was proportional to diamide concentration (0.01-1 mM) and duration of preincubation (up to 2 h). Dithiothreitol (5 mM, 1 h) reversed most of the basal ATPase activation and restored Ca2+ sensitivity. Other sulfhydryl reagents produced a similar effect but also produced inhibition of total ATPase. In intact cell preparations, diamide produced a slow tonic contraction, consistent with myofibril activation. In the perfused rat heart, 1 mM diamide slowly increased diastolic ventricular pressure; this increase was partially reversed by dithioerythritol. In isolated rat heart myocytes, 1 mM diamide produced a slow tonic contraction, increased contractility in response to stimulation. Cardiocytes superfused for 1 h with buffer containing EGTA to deplete Ca2+ did not contract in response to stimulation but showed a slow tonic contraction with diamide. This contraction could be slowly and only partially reversed by dithioerythritol. Response to stimulation was restored by addition of Ca2+. The results show that diamide can produce contraction in viable cells. This contraction does not require extracellular Ca2+ and is unlikely to involve intracellular Ca2+. The direct activation of myofibrillar ATPase may contribute to the increased myocardial stiffness seen in ischemia and to ischemic contracture.
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PMID:Reversible elimination of myofibrillar Ca2+ sensitivity by diamide and other sulfhydryl reagents: comparison with reversible contracture produced in intact cells. 214 65

The pH dependence of the Ca2(+)-transporting ATPase of bovine cardiac sarcolemma was determined in a membrane vesicle preparation. The maximal velocity (Vmax) at saturating external Ca2+ showed a sigmoidal pH dependence with maximal values in the 6.0-6.5 range, a half-maximal value at 7.2 and minimal (less than or equal to 15%) values at pH greater than or equal to 8.0. The apparent affinity for Ca2+ (1/Km) varied over 10(4)-fold for 6.0 less than or equal to pH less than or equal to 8.5, increasing with increasing pH. Plots of log(1/Km) vs. pH were biphasic. In the acid range (6.0 less than or equal to pH less than or equal to 7.2), a slope of 2.6 was observed for the calmodulin-activated form of the pump. For 7.2 less than or equal to pH less than or equal to 8.5, a slope of 0.5 was observed. At pH 7.4, the Km is approx. 48 +/- 19 nM. The Ca2+ pump of cardiac sarcoplasmic reticulum in the same preparation had a Km of 304 +/- 115 nM and showed a similar pH dependence except that the slope in the acid range was 1.7. When calmodulin was removed from the sarcolemmal pump, its Km was raised to approx. 1.0 microM, the slope in the acid range was reduced to 1.7 and the Vmax was markedly reduced. The results are explicable in terms of a model in which each of the two Ca2+ binding sites on the pump contains two buried COO- groups responsible for high affinity. The Km effect is explained by 2 H+ vs. 1 Ca2+ competition for occupation of each of the two cytoplasmically-oriented translocators (4 H+ vs. 2 Ca2+). The Vmax effect is explained by counter-transport of H+. The findings are considered in terms of the published amino acid sequence of the cardiac sarcolemmal pump and recent site-directed mutagenesis vs. function studies identifying the Ca2+ binding site in the skeletal sarcoplasmic reticulum pump. The kinetic data are also applied to pump behavior under conditions of ischemia and acidosis.
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PMID:The pH dependence of the cardiac sarcolemmal Ca2(+)-transporting ATPase: evidence that the Ca2+ translocator bears a doubly negative charge. 214 13

In an attempt to clarify the mechanism of sarcoplasmic reticulum (SR) dysfunction during the genesis of irreversible damage in the ischemic-reperfused myocardium, the changes in SR Ca2(+)-pumping ATPase (Ca2(+)-activated, Mg2(+)-dependent ATPase; Ca2(+)-ATPase) activity were studied during ischemia and subsequent reperfusion in the isolated perfused guinea pig heart preparation and correlated with the accumulation of calcium in the myocardium. Although the SR Ca2(+)-ATPase activity was not affected by ischemia of 40 min, reperfusion of the ischemic myocardium resulted in a definite time-dependent decrease in the enzyme activity. The reduction of SR Ca2(+)-ATPase activity was associated with a concomitant decrease in the enzyme concentration in the isolated SR and was in a good correlation with a substantial accumulation within the myocardium. As the results indicated the possibility that proteolytic degradation by a calcium-activated protease(s) was responsible for the reduction of enzyme activity, we examined for the possible involvement of calcium-activated neutral protease (CANP). However, SR Ca2(+)-ATPase obtained either from the normal hearts or from the hearts after 40-min ischemia was found to be quite resistant to proteolytic actions of the two forms of CANP, i.e., microCANP and mCANP partially purified from the guinea pig heart. These results suggest that a destructive process leading to the degradation of SR Ca2(+)-ATPase is activated by reperfusion, but not by ischemia per se, and that CANP is not implicated in the degradation of SR Ca2(+)-ATPase.
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PMID:Degradation of sarcoplasmic reticulum calcium-pumping ATPase in ischemic-reperfused myocardium: role of calcium-activated neutral protease. 214 70

A normal single left coronary artery was found in a high school boy who died suddenly after Rugby football practice. He had an infarct lesion in the posterior wall where there was no perfusion because of the absence of the right coronary artery. There was no significant lesion in the anterior wall except for contraction band necrosis. Myoglobin diffusion paralleled the extent of necrosis. The case was useful in evaluating the effects of ischemia on a human subject because variations due to personality and postmortem changes were not involved. Actomyosin ATPase activity was not different among the various infarct and non-infarct regions examined except in one infarct region where it was higher.
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PMID:Sudden death case of single coronary artery with special reference to the effect of ischemia on actomyosin. 215 Apr 22

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