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

It is widely accepted that the ionic movement across the different membrane systems (i.e. sarcolemma, sarcoplasmic reticulum, mitochondria), plays a major role on heart muscle metabolism. On the other hand, neither the relative role nor the associated energy expenditure of those mechanisms have been definitively established. Biochemical and biophysical measurements of the different ion exchange mechanisms, have provided data leading to the postulation of different models for both resting and active metabolism of the heart muscle. The present work analyzes, from an energetic standpoint, available biochemical and biophysical data from the literature calculating the range of energy expenditure that should be attributable to each mechanism. Sodium, potassium and calcium movements during either resting and/or active state are particularly analyzed and the fractional role of various organelles (sarcolemma, sarcoplasmic reticulum and mitochondria) discussed. From this analysis and the known amount of energy released (or the amount of oxygen consumed) by the muscle it is possible to determine whether there is enough energy for a given model of ionic exchange during the excitation contraction process. In addition to this analysis a comparatively short review of energetic studies performed under pathological conditions is also presented. In particular, the pathological conditions analyzed are those with an energetic compromise such as heart hypertrophy, ischemia and anoxia in which the alteration of ionic transport mechanisms seems to be playing a major role.
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PMID:[Energetics of ionic behavior in heart muscle contraction. Physiologic and physiopathologic aspects]. 820 34

Sodium tanshinone IIA sulfonate (STS) is a derivative of tanshinone IIA. The latter is a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza. Liquid chromatographically pure STS was found to reduce myocardial infarct size by 53.14 +/- 22.79% relative to that in the saline control in a rabbit 1 hr-ischemia and 3 hr-reperfusion model. This effect was comparable to that of Trolox (a better characterized antioxidant serving as a reference cytoprotector), which salvaged the myocardium in the same infarct model by 62.13 +/- 18.91%. Also, like Trolox, STS did not inhibit oxygen uptake by xanthine oxidase (XO), a key enzyme in free radical generation. However, in contrast to Trolox, STS significantly prolonged the survival of cultured human saphenous vein endothelial cells but not human ventricular myocytes in vitro when these cells were separately exposed to XO-generated oxyradicals. Note that the endothelium is recognized to be a key site of oxidant generation and attack. Our findings in vitro and in vivo support the interpretation that STS is a cardioprotective substance, and that it may exert a beneficial effect on the clinically important vascular endothelium.
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PMID:Effect of sodium tanshinone IIA sulfonate in the rabbit myocardium and on human cardiomyocytes and vascular endothelial cells. 827 65

In our miniature swine model of brain retraction ischemia under conditions simulating the neurosurgical operating room, we studied the effects of bolus mannitol (2 g/kg) administration on cerebral blood flow, blood pressure, blood viscosity, hematocrit, sodium, and potassium serially for 4 hours following administration, at which time a second bolus was administered. Both viscosity and hematocrit were significantly decreased transiently following both the first and second boluses. Sodium was decreased for 30 minutes following the first bolus, 15 minutes following the second bolus, and increased at 150 minutes and later following the second bolus. There was a mild decrease in blood pressure and a mild increase in cerebral blood flow following mannitol, but little difference between the first hour following a bolus (when the viscosity and hematocrit were decreased) and hours 2-4 (when they were near baseline). Mannitol's effects on blood pressure and cerebral blood flow probably depend on factors in addition to its effects on blood viscosity and hematocrit. The results are discussed in light of previous findings that bolus mannitol administration may improve cerebral blood flow in ischemia, but does not appear to benefit the preservation of brain electrical activity.
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PMID:Effects of mannitol on cerebral blood flow, blood pressure, blood viscosity, hematocrit, sodium, and potassium. 845 86

We used metabolic, enzymatic, and functional end points to compare the protective properties of continuous warm and intermittent cold cardioplegic infusion in isolated, blood-perfused rat hearts. After excision, hearts (n = 12 per group) were preserved for 3 hours by one of the following cardioplegic procedures: (1) continuous infusion of warm (37 degrees C) blood cardioplegic solution prepared by mixing Fremes' solution with rat arterial blood in a ratio of 1:4, (2) continuous infusion of warm (37 degrees C) crystalloid cardioplegic solution prepared by mixing Fremes' solution with bicarbonate buffer solution in a ratio of 1:4, or (3) intermittent infusion of cold (20 degrees C) St. Thomas' Hospital cardioplegic solution number 2 infused for 3 minutes every 30 minutes during a 3-hour period of ischemia. In the continuous-infusion cardioplegic groups, the solution was infused through the aorta at a flow rate of 0.8 ml.min-1.gm-1 heart. At the end of the 3-hour preservation period, myocardial sodium-potassium adenosine triphosphatase activity (an index of ion-exchange activity) was assessed in six hearts in each group. The remaining hearts in each group were then aerobically perfused at 37 degrees C with arterial blood (from a support rat) for a further 50 minutes, during which time they were atrially paced at 320 beats/min. At the end of this period, left ventricular developed and end-diastolic pressures were assessed with an intraventricular balloon; the hearts were then freeze-clamped and taken for the measurement of tissue adenosine triphosphate and creatine phosphate content. Hearts (n = 6) aerobically perfused with blood for 50 minutes (no cardioplegic infusion) served as control preparations. At a balloon volume of 180 microliters, the mean final values for left ventricular developed pressure in the continuous warm blood, continuous warm crystalloid, and intermittent cold cardioplegic groups were 98 +/- 5 mm Hg (p < 0.05), 70 +/- 5 mm Hg, and 78 +/- 5 mm Hg, respectively. This was compared with 122 +/- 5 mm Hg in control hearts (p < 0.05 vs the rest). For left ventricular end-diastolic pressure, the corresponding values were 33 +/- 3 mm Hg, 32 +/- 6 mm Hg, and 14 +/- 4 mm Hg (p < 0.05), respectively. The control value was 16 +/- 3 mm Hg (p < 0.05 vs continuous warm blood and continuous warm crystalloid groups). Tissue content of adenosine triphosphate was similarly reduced to approximately 50% of control values in all groups, and creatine phosphate content fully recovered in all groups. Sodium-potassium adenosine triphosphatase activity was poorly preserved in continuous warm crystalloid-treated hearts (0.012 +/- 0.003 vs 0.030 +/- 0.008 mumol inorganic phosphate-mg-1.min-1.
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PMID:Continuous warm versus intermittent cold cardioplegic infusion: a comparison of energy metabolism, sodium-potassium adenosine triphosphatase activity, and postischemic functional recovery in the blood-perfused rat heart. 880 Jan 70

In order to prevent cyclosporine nephrotoxicity in the ischemic kidney, pentoxifylline was used in a rat model. Seventy-two rats were divided into six groups according to treatment after right nephrectomy: Group I was the control, group II was treated with 25 mg/kg cyclosporine, group III underwent renal ischemia for 45 min, group IV was given 25 mg/kg cyclosporine and subjected to renal ischemia, and group V was subjected to renal ischemia and given 45 mg/kg pentoxifylline (repeated at 12, 36, and 48 hr), group VI underwent renal ischemia and was then given both cyclosporine and pentoxifylline. BUN, creatinine, and potassium levels were significantly elevated 24 hr after cyclosporine (group II), ischemia (group III), and cyclosporine and ischemia (group IV). Sodium levels remained unaffected. BUN levels normalized in all but groups III and IV after 48 hr. Creatinine levels normalized in all but group IV after 48 hr. Creatinine clearance fell in all groups and remained low even after 48 hr. Pentoxifylline prevented dramatic rises in BUN and creatinine and levels nearly normalized after 48 hr. It also histologically prevented extensive tissue damage seen after ischemia. In conclusion, pentoxifylline has a protective effect upon the kidney when subjected to cyclosporine in the presence of ischemia.
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PMID:Cyclosporine nephrotoxicity in the ischemic kidney and the protective effect of pentoxifylline--a study in the rat. 882 91

Massive striatal dopamine release during cerebral ischaemia has been implicated in the resulting neuronal damage. Sodium influx is an early event in the biochemical cascade during ischaemia and blockade of sodium channels may increase resistance to ischaemia by reducing energy demand involved in compensation for sodium and potassium fluxes. In this study, we have determined the effects of opening and blockade of voltage-gated sodium channels on hypoxia/hypoglycaemia-induced dopamine release. Slices of rat caudate nucleus were maintained in a slice chamber superfused by an oxygenated artificial cerebrospinal fluid containing 4 mM glucose. Ischaemia (hypoxia/hypoglycaemia) was mimicked by a switch to a deoxygenated artificial cerebrospinal fluid containing 2 mM glucose and dopamine release was measured using fast cyclic voltammetry. In drug-free (control) slices, there was a 2-3 min delay after the onset of hypoxia/hypoglycaemia followed by a rapid dopamine release event which was associated with anoxic depolarization. In slices treated with the Na+ channel opener, veratridine (1 microM), the time to onset of dopamine release was shortened (101 +/- 20 s, compared with 171 +/- 8 s in controls, P < 0.05). Conversely, phenytoin (100 microM), lignocaine (200 microM) and the highly selective sodium channel blocker, tetrodotoxin (1 microM) markedly delayed and slowed dopamine release vs paired controls. In the majority of cases, dopamine release was biphasic after sodium channel blockade: a slow phase preceded a more rapid dopamine release event. The latter was associated with anoxic depolarization. Neither the fast nor the slow release events were affected by pretreatment with the selective dopamine uptake blocker GBR 12935 (0.2 microM), suggesting that uptake carrier reversal did not contribute to these events. In conclusion, sodium channel antagonism delays and slows hypoxia/hypoglycaemia-induced dopamine release in vitro. Furthermore, sodium channel blockade delays anoxic depolarization and its associated neurotransmitter release, revealing an earlier dopamine release event that does not result from reversal of the uptake carrier.
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PMID:Sodium channel blockade unmasks two temporally distinct mechanisms of striatal dopamine release during hypoxia/hypoglycaemia in vitro. 933 Mar 62

This work determined Ca2+ transport processes that contribute to the rise in cytosolic Ca2+ during in vitro ischemia (deprivation of oxygen and glucose) in the hippocampus. The CA1 striatum radiatum of rat hippocampal slices was monitored by confocal microscopy of calcium green-1. There was a 50-60% increase in fluorescence during 10 min of ischemia after a 3 min lag period. During the first 5 min of ischemia the major contribution was from Ca2+ entering via NMDA receptors; most of the fluorescence increase was blocked by MK-801. Approximately one-half of the sustained increase in fluorescence during 10 min of ischemia was caused by activation of Ca2+ release from mitochondria via the mitochondrial 2Na+-Ca2+ exchanger. Inhibition of Na+ influx across the plasmalemma using lidocaine, low extracellular Na+, or the AMPA/kainate receptor blocker CNQX reduced the fluorescence increase by 50%. The 2Na+-Ca2+ exchange blocker CGP37157 also blocked the increase, and this effect was not additive with the effects of blocking Na+ influx. When added together, CNQX and lidocaine inhibited the fluorescence increase more than CGP37157 did. Thus, during ischemia, Ca2+ entry via NMDA receptors accounts for the earliest rise in cytosolic Ca2+. Approximately 50% of the sustained rise is attributable to Na+ entry and subsequent Ca2+ release from the mitochondria via the 2Na+-Ca2+ exchanger. Sodium entry is also hypothesized to compromise clearance of cytosolic Ca2+ by routes other than mitochondrial uptake, probably by enhancing ATP depletion, accounting for the large inhibition of the Ca2+ increase by the combination of CNQX and lidocaine.
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PMID:Cytosolic Ca2+ changes during in vitro ischemia in rat hippocampal slices: major roles for glutamate and Na+-dependent Ca2+ release from mitochondria. 1021 90

Using in vivo microscopy red blood cell (RBC) velocities, functional capillary density (FCD) and capillary diameters were estimated after inducing acute pancreatitis by intraductal infusion of sodium taurocholate (0.8 ml; 4%) or after topical superfusion of the pancreas with ET-1 (100 pmol). Sodium taurocholate mediated a significant decrease in RBC velocities between 50 and 70%, transient decrease in capillary diameters by 10%, and a sustained decrease in FCD between 60 and 70% paralleled by a dramatic heterogeneity in blood flow. Topical superfusion of the exteriorized pancreas with ET-1 caused a significant decrease in RBC velocities between 65 and 75%, a sustained decrease in capillary diameters by 10%, and a decrease in FCD by 45% accompanied by an increase in flow heterogeneity. Following sodium taurocholate infusion pancreas histology revealed a severe edema and sublobular acinar cell necrosis, while topical ET-1 application displayed a severe edema of the pancreas with focal acinar cell necrosis. Thus, ET-1 mediated a deterioration of the pancreatic microcirculation, which is similar to the microcirculatory failure found in sodium taurocholate-induced experimental pancreatitis and was associated with focal acinar cell necrosis. We are thus inclined to hypothesize that endothelin released by injured endothelial cells during acute biliary pancreatitis promotes microcirculatory failure and ischemia in acute pancreatitis, eventually leading to acinar cell necrosis.
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PMID:ET-1 induces pancreatitis-like microvascular deterioration and acinar cell injury. 1042 33

Sodium-hydrogen exchange (Na-H exchange) is a major regulator of intracellular pH and is one of the major mechanisms for restoring pH after ischemia-induced intracellular acidosis. However, activation of Na-H exchange during ischemia and reperfusion is also involved in paradoxical induction of cell injury. This likely reflects the fact that activation of the exchanger is closely coupled to sodium influx and, as a consequence, to elevation in intracellular calcium concentrations through sodium-calcium exchange. In addition to intracellular acidosis, other factors can also stimulate the exchanger, including various autocrine and paracrine factors, such as endothelin-1, angiotensin II, alpha(1)-adrenergic agonists, as well as toxic agents, such as hydrogen peroxide and lysophosphatidylcholine. Although at least six Na-H exchange isoforms have thus far been identified, it appears that the 1 subtype, termed NHE1, is the predominant isoform in the mammalian myocardium. Effective pharmacological inhibitors of Na-H exchange, including those that are NHE1 specific, have been extensively demonstrated to protect the ischemic and reperfused myocardium in terms of improved systolic and diastolic function, preservation of cellular ultrastructure, attenuation of the incidence of arrhythmias, and reduction of apoptosis. Moreover, the salutary effects of these agents have been demonstrated using a variety of experimental models as well as animal species, suggesting that the role of Na-H exchange in mediating injury is not species specific. Thus, Na-H exchange represents an important target for pharmacological intervention in attenuation of ischemia and reperfusion-induced cardiac injury. Coupled with the low potential for toxicity of the agents, Na-H exchange inhibition could emerge as an effective therapeutic strategy in cardiac disorders, particularly involving conditions associated with ischemia and reperfusion.
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PMID:Mechanisms of protection of the ischemic and reperfused myocardium by sodium-hydrogen exchange inhibition. 1048 Dec 12

Small reductions in temperature have been shown to improve neurologic recovery after ischemia. We have examined the effect of temperature on biochemical and physiological changes during hypoxia using rat hippocampal slices as a model system. The postsynaptic population spike recorded from the CA1 pyramidal cell region of slices subjected to 7 min of hypoxia with hypothermia (34 degrees C) recovered to 73% of its prehypoxic level; slices subjected to the same period of hypoxia at 37 degrees C did not recover. After 7 min of hypoxia ATP fell to 48% of its prehypoxic concentration at 34 degrees C and 30% at 37 degrees C. Potassium fell to 86% during 7 min of hypoxia with hypothermia, this compares to a fall to 58% at 37 degrees C. The increase in sodium after 7 min of hypoxia was also attenuated by hypothermia (133% vs. 163% of its prehypoxic concentration). When the hypoxic period was shortened to 3 min (37 degrees C) the population spike recovered to 94%. If the temperature was increased to 40 degrees C there was only 7% recovery of the population spike after 3 min of hypoxia. With hyperthermia (40 degrees C), ATP fell to 33% after 3 min of hypoxia, this compares to 81% at normothermia. Potassium fell to 76% after 3 min of hypoxia with hyperthermia, this compares to 91% at 37 degrees C. Sodium concentrations increased with hyperthermia before hypoxia, at 3 min of hypoxia there was no significant difference between the hyperthermic and normothermic tissue; there was a large increase in sodium with hyperthermia after 5 min of hypoxia (209% vs. 146%). We conclude that the improved recovery after hypothermic hypoxia is at least in part due to the attenuated changes in ATP, potassium and sodium during hypoxia and that the worsened recovery with hyperthermia is due to an exacerbation of the change in ATP, potassium and sodium concentrations during hypoxia.
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PMID:Effect of small changes in temperature on CA1 pyramidal cells from rat hippocampal slices during hypoxia: implications about the mechanism of hypothermic protection against neuronal damage. 1053 70


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