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

Although several studies suggest that hepatic graft failure after cold ischemia results from nonparenchymal cell damage, other data indicate that hepatocellular ATP content is significantly correlated with the transplantation success rate. In this study, we have conducted a systematic investigation of various aspects of cell viability and function of isolated hepatocytes stored at 4 degrees C for 24 and 48 hr in either University of Wisconsin solution or Hanks' HEPES buffer, a control solution clinically unsuitable for organ preservation. After 24 hr, hepatocytes stored in Hanks' HEPES buffer had viability (measured by trypan blue exclusion and ALT and lactic dehydrogenase leakage), transport function (measured by 22Na+ and [3H]taurocholate uptake) and cell size similar or only slightly altered when compared with freshly isolated and University of Wisconsin solution-stored hepatocytes. ATP content was decreased in both groups; however, the reduction was much greater in Hanks' HEPES buffer-stored cells. Furthermore, ATP regenerating capacity was greatly reduced in Hanks' HEPES buffer- stored but not in University of Wisconsin solution-stored hepatocytes. By 48 hr viability and function of Hanks' HEPES buffer-stored hepatocytes were decreased; University of Wisconsin solution afforded partial protection. When examined by light and electron microscopy, cells stored in both University of Wisconsin solution and Hanks' HEPES buffer for 24 hr appeared essentially normal except for the presence of numerous membrane blebs in the Hanks' HEPES buffer group. Tissue sections of livers preserved in Hanks' HEPES buffer but not in University of Wisconsin solution revealed the presence of extensive amounts of blebs in the sinusoidal lumen and loss of endothelial elements.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional and morphological features of isolated hepatocytes preserved in University of Wisconsin solution. 186 Jun 90

The effects of metabolic acidosis and alkalosis in the initial reperfusate on post-ischemic stunned myocardium were investigated in isolated rat hearts. Metabolic acidosis and alkalosis were produced by altering the doses of artificial buffer (Tris) in place of sodium bicarbonate. All hearts were subjected to global ischemia for 15 min at 37 degrees C. The initial reperfusate under study was given during the subsequent 10 min of reperfusion, just prior to release of the aortic clamp. After that, reperfusion using normal Krebs-Henseleit buffer solution was carried out for 40 min. The acidotic initial reperfusate (pH 6.8) resulted in better protection than the alkalotic initial reperfusate (pH 7.8), as demonstrated by 1) a higher recovery of aortic flow (80.6% +/- 3.8% vs 32.7% +/- 4.8%, p less than 0.01), 2) a smaller leakage of creatine kinase during the initial reperfusion phase (6.0 +/- 0.7 vs 14.6 +/- 2.1 IU/10 min/g dry weight, p less than 0.05) and during the post-ischemic Langendorff perfusion phase (8.8 +/- 1.7 vs 37.3 +/- 5.2 IU/10 min/g dry weight, p less than 0.05), and 3) a lower myocardial water content at the end of reperfusion (84.8% +/- 0.2% vs 85.7% +/- 0.3%, p less than 0.05). Not only Tris buffer system, but also HEPES buffer system indicated that acidotic initial reperfusate was effective to protect against myocardial injury. These results suggest that 1) the extracellular pH during initial reperfusion profoundly influences the reversible myocardial dysfunction (stunned myocardium), and 2) the acidotic initial reperfusate improves post-ischemic myocardial performance.
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PMID:Beneficial actions of acidotic initial reperfusate in stunned myocardium of rat hearts. 195 71

We investigated the hypothesis that an accelerated Na+o-H+i exchange on reperfusion may lead to a displacement of the 3[Na+] [Ca2+]i/o equilibrium in favor of an arrhythmogenic rise in cytosolic [Ca2+]. Supporting evidence was obtained by subjection of isolated rat hearts to 15 minutes of low-flow (5% of control) ischemia and 2 minutes of reperfusion in the presence of a Krebs-Henseleit HEPES buffer (pH 7.4) containing lactate (10 mM). At first, the [HEPES] was fixed at 5 mM; then, 2 minutes before reflow, either the [HEPES] was varied from 50 to 1 mM to slow H+o washout, or increasing concentrations of 5-(N,N-dimethyl)-amiloride (Ki 7 microM) or 5-(N,N-hexamethylene)-amiloride (Ki 0.2 microM) were added for inhibition of Na(+)-H+ exchange. In each case, reperfusion ventricular arrhythmias were reduced by 69-73% (p less than 0.001).
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PMID:Effects of proton buffering and of amiloride derivatives on reperfusion arrhythmias in isolated rat hearts. Possible evidence for an arrhythmogenic role of Na(+)-H+ exchange. 215 34

Cellular edema and cardiac arrhythmias are often closely related to intracellular ionic alterations and, moreover, are an actual problem of clinical cardioplegia and ischemia of the heart. In order to investigate whether the clinically widely used cardioplegic solution of the St. Thomas' Hospital may predispose for these complications, membrane potential (EM), intracellular pH (pHi), and intracellular sodium and potassium activity (aiNa- and aiK) in sheep heart Purkinje fibres were directly measured by means of neutral-carrier ion-selective microelectrodes during equilibration of the fibres' extracellular space with the cardioplegic solution. The experimental temperature was 35 degrees C throughout. During control conditions under superfusion of a HEPES-buffered Tyrode solution EM was -74.4 +/- 5.1 mV (n = 39), pHi was 7.18 +/- 0.05 (n = 16), and aiNa and aiK were 7.6 +/- 1.4 mmol/l (n = 15) and 118.9 +/- 4.6 mmol/l (n = 15) respectively. Superfusing the Purkinje strand for 10 minutes with the cardioplegic St. Thomas' solution led to a depolarization to -57.3 +/- 4.7 mV (n = 21), a slight aiNa decrease to 6.7 +/- 1.6 mmol/l (n = 15; p less than 0.01; cardioplegic solution without procaine) and an increase of aiK to 127.1 +/- 4.4 mmol/l (n = 6; p less than 0.01). pHi needed 15 minutes to reach a steady state value of 7.25 +/- 0.05 (n = 9). The alterations on post-cardioplegic reperfusion with Tyrode solution were reversible within 15 minutes. Simulation of the clinical situation of ice-cold application of the solution by inhibiting the cellular Na/K pump via 0.1 mmol/l dihydroouabaine added to the St. Thomas' solution resulted in a marked increase of aiNa to 10.7 +/- 1.5 mmol/l (n = 6; p less than 0.01; no procaine) during cardioplegic superfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracellular pH, Na+- and K+-activities at the onset of St. Thomas' cardioplegia: a study with ionselective microelectrodes. 323 61

A sustained high voltage-activated (HVA), nifedipine- and cadmium-sensitive calcium current and a sustained calcium action potential (AP) were recorded from horizontal cells isolated from catfish retina. pH indicator dyes showed that superfusion with NH4Cl alkalinized these cells and that washout of NH4Cl or superfusion with Na-acetate acidified them. HVA current was slightly enhanced during superfusion of NH4Cl but was suppressed upon NH4Cl washout or application of Na-acetate. When 25 mM HEPES was added to the patch pipette to increase intracellular pH buffering, the effects of NH4Cl and Na-acetate on HVA current were reduced. These results indicated that intracellular acidification reduces HVA calcium current and alkalinization increases it. Sustained APs, recorded with high resistance, small diameter microelectrodes, were blocked by cobalt and cadmium and their magnitude varied with extracellular calcium concentration. These results provide confirmatory evidence that the HVA current is a major component of the AP and indicate that the AP can be used as a measure of how the HVA current can be modified in intact, undialyzed cells. The duration of APs was increased by superfusion with NH4Cl and reduced by washout of NH4Cl or superfusion with Na-acetate. The Na-acetate and NH4Cl washout-dependent shortening of the APs was observed in the presence of intracellular BAPTA, a calcium chelator, IBMX, a phosphodiesterase inhibitor, and in Na-free or TEA-enriched saline. These findings provide supportive evidence that intracellular acidification may directly suppress the HVA calcium current in intact cells. Intracellular pH changes would thereby be expected to modulate not only the resting membrane potential of these cells in darkness, but calcium-dependent release of neurotransmitter from these cells as well. Furthermore, this acidification-dependent suppression of calcium current could serve a protective role by reducing calcium entry during retinal ischemia, which is usually thought to be accompanied by intracellular acidosis.
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PMID:Modulation of a sustained calcium current by intracellular pH in horizontal cells of fish retina. 768 44

A marked decrease in the activity of the amiloride-sensitive Na+/H+ exchanger has been demonstrated in hearts from streptozotocin (STZ)-induced diabetic rats. The aim of this study was to investigate the contribution of other specific sarcolemmal transport mechanisms to intracellular pH (pHi) recovery upon reperfusion in STZ-induced diabetic rat hearts and their relation to recovery of ventricular function. Isovolumic rat hearts were submitted to a zero-flow ischemic period of 28 min at 37 degrees C and then reperfused for 28 min. The time course of pHi decline during ischemia and of recovery on reperfusion was followed by means of 31P-labeled NMR. The perfusion buffers used were either HEPES or CO2/HCO3-. An HCO3(-)-dependent (amiloride-insensitive) mechanism contributed to pHi recovery after ischemia in the diabetic rat hearts. Even when the Na+/H+ exchanger was blocked by amiloride in nominally HCO3(-)-free solution, a rapid rise in pHi occurred during the first 3 min of reperfusion. The early rise in pHi was reduced by external lactate and inhibited by alpha-cyano-4-hydroxycinnamate. This suggested that a coupled H(+)-lactate efflux may be a major mechanism for acid extrusion in the initial stage of reperfusion. The observation of a higher functional recovery on reperfusion in diabetic hearts is in accordance with previous studies using HCO3- buffer. However, this study shows that a good recovery of function occurred even more rapidly in diabetic hearts receiving HEPES-buffered solution than in those receiving HCO3(-)-buffered solution. This suggests that the HCO3(-)-dependent mechanism of regulation may be depressed in diabetic rat hearts.
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PMID:Mechanisms of intracellular pH regulation during postischemic reperfusion of diabetic rat hearts. 785 41

Prevention of myocardial acidosis during global ischemia in operative cardiopreservation was explored in two series of dogs where acid-base control was the only variable. A specifically designed aminosulfonic acid buffer composition, 3:1 molar equivalents NaMOPS to HEPES, 0.2 mol/L, was compared with NaHCO3 (pH 8). Dissolved in standard cardioplegic solution it was given every 30 minutes by coronary infusion at 20 degrees C during 3 hours of global ischemia. Glass electrode intramyocardial pH, adenosine triphosphate (ATP) level, left ventricular contractility (Dp/Dt) and compliance (-Dp/Dt), and other cardiovascular parameters were measured frequently throughout ischemia and for 75 minutes thereafter. In the buffer group (n = 6) myocardial pH remained above entry levels throughout the study period, adenosine triphosphate level remained normal during ischemia, and Dp/Dt and -Dp/Dt at 75 minutes of reperfusion were above entry levels. In the NaHCO3 group (n = 6) pH declined and remained depressed throughout ischemia, adenosine triphosphate level fell steadily and significantly throughout the experiment, and Dp/Dt and -Dp/Dt never regained entry levels. The difference in each parameter between the two groups was statistically significant (p < 0.05). We conclude that control of myocardial acid-base equilibrium alone during global ischemia will preserve myocardial function and minimize reperfusion injury.
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PMID:Aminosulfonic acid buffer preserves myocardium during prolonged ischemia. 801 Aug 7

Excessive or prolonged stimulation of N-methyl-D-aspartate (NMDA) receptors appears to play an important role in many neurodegenerative processes in brain through a process known as excitotoxicity. This study examined the effects of ethanol on NMDA receptor-mediated excitotoxicity in primary neuronal cultures obtained from embryonic rat whole brain. Neurotoxicity was quantitated by measuring the amount of lactate dehydrogenase released into the media during a 20-hr time period following NMDA washout. Exposure of 12- to 14-day-old cultures to NMDA in Mg(2+)-free HEPES buffer (pH 7.4) for a 25-min period resulted in a concentration-dependent toxicity (EC50 = 54 microM). Time-course experiments showed that exposure to NMDA for as little as 5 min was excitotoxic and reached a plateau after a 20-min exposure period. Preincubation of the cultures with ethanol (25 to 200 mM) resulted in a concentration-dependent inhibition of NMDA-mediated toxicity with approximately 38% inhibition produced by 25 mM ethanol and essentially complete inhibition at 200 mM ethanol (IC50 = 60 mM). Increasing the glycine concentration to 100 microM did not potentiate NMDA neurotoxicity or antagonize the neuroprotective effect of ethanol. NMDA-Mediated excitotoxicity was reduced by approximately 50% by the glycine antagonist 7-chlorokynurenate (50 microM). Ethanol (50 mM) reduced NMDA neurotoxicity similar to 7-chlorokynurenate, and the two together produced greater inhibition than either alone. These results show that intoxicating concentrations of ethanol can potently inhibit NMDA receptor-mediated excitotoxicity and may have important implications in terms of ethanols interactions with brain trauma, ischemia, and other neuropathologies associated with NMDA receptor-mediated neurotoxicity.
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PMID:Ethanol inhibits NMDA receptor-mediated excitotoxicity in rat primary neuronal cultures. 838 26

A Na(+)-HCO3- coinflux carrier and the Na(+)-H+ antiport have both been shown to contribute to recovery from intracellular acidosis in cardiac tissue. We have investigated the participation of these mechanisms as well as metabolite (lactate and CO2) washout in the recovery of pHi after myocardial ischemia. Isovolumic ferret hearts were Langendorff-perfused with either HCO3(-)-buffered or nominally HCO3(-)-free (HEPES-buffered) medium at 30 degrees C. pHi was estimated from the chemical shift of the 31P-nuclear magnetic resonance signal of intracellular PO4-, and net H+ efflux rates were calculated at pHi 6.80. The H+ efflux rate during reperfusion, after 10 minutes of global ischemia, was 15.5 +/- 1.9 mmol.l-1 x min-1 (n = 10) in hearts perfused with HCO3(-)-buffered medium and 8.2 +/- 1.5 mmol.l-1 x min-1 (n = 9, p < 0.01) in hearts perfused with HEPES-buffered medium. HCO3- influx, assessed either by inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (20 microM) or by initially perfusing hearts with HEPES-buffered medium but reperfusing with HCO3(-)-buffered medium, accounted for 3.5-4.9 mmol.l-1 x min-1, and CO2 efflux accounted for 3.8-6.2 mmol.l-1 x min-1 of the additional H+ efflux in HCO3(-)-buffered medium. H(+)-coupled lactate efflux, measured by NAD(+)-linked spectrophotometric assay and inhibited by the sarcolemmal monocarboxylate transport inhibitor 4,4'-dibenzamidostilbene-2,2'-disulfonate (0.25 mM), contributed 3.7-6.2 mmol.l-1 x min-1. H+ efflux via the 5-(N-ethyl-N-isopropyl)amiloride-sensitive Na(+)-H+ antiport was 1.0-2.9 mmol.l-1 x min-1. pHi recovery after ischemia is therefore principally mediated by metabolite (lactate and CO2) washout. Na(+)-coupled acid extrusion contributed approximately 35% of total H+ efflux in this system. However, the associated Na+ entry (approximately 5 mmol.l-1 x min-1) may contribute to Ca2+ overload after reperfusion.
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PMID:Mechanisms of pHi recovery after global ischemia in the perfused heart. 838 98

Local vasodilation in response to hypoxia or ischemia improves perfusion and O2 supply of the affected tissue. This local vasodilation thus constitutes the most important mechanism in the prevention of ischemic cell injury. The regulation of vascular tone has mainly been attributed to changes of cytoplasmatic Ca2+ ((Ca2+)i) concentrations in vascular smooth muscle cells. The mechanism underlying these changes has not, however, been elucidated so far. Using aortic strips of guinea pigs (transversally cut in spirals; normal Tyrode, in mM: NaCl 150, KCl 4.5, MgCl2 2, CaCl2 2.5, glucose 10; buffered with 10 mM HEPES at pH 7.4; equilibrated with 100% O2 at 31 degrees C) the authors could show that metabolic blockade (glucose replaced by 10 mM 2-deoxyglucose (DOG) led to a relaxation of the preparation. Thus, in four experiments, resting tension decreased from 0.75 g by 27% +/- 12% within two hours (% of maximal contractile force developed by each preparation when depolarized with 43 mM KCl and 101.5 mM NaCl). When the same experiment was carried out in the presence of 1 mM tolbutamide (a known blocker of ATP-dependent K+ channels) in vascular smooth muscle no such relaxation could be seen (n = 4). Furthermore, in the same type of preparation, similar results have been obtained upon hypoxic relaxation (100% O2 replaced by 100% N2), where 1 mM tolbutamide also prevented vasodilation. Thus, hypoxic/ischemic vasodilation in response to glycolytic inhibition (DOG) and hypoxia (N2) is based upon the opening of K+ ATP channels and hence can be prevented by sulfonylureas (the opening of K+ ATP channels would lead to hyperpolarization (increased K+ conductance, Goldmann equation), thus diminishing the open probability of voltage-gated Ca2+ channels with subsequent vasodilation). This inhibition by sulfonylureas of vasodilative response to ischemia may also constitute the so far unknown cause of the increased cardiovascular mortality seen under sulfonylurea treatment.
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PMID:Vasodilative response to hypoxia and simulated ischemia is mediated by ATP-sensitive K+ channels in guinea pig thoracic aorta. 844 33


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