Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ischemia-reperfusion syndrome, first described by Haimovici in 1960, is a severe complication following surgery for acute ischemia. We evaluated the incidence of this complication in 264 patients operated on between 1972 and 1981 (1st group) and compared it with another of 392 patients operated on between 1982 and 1991 (2nd group), our aim being to assess the effects of pharmacological prophyiaxis based on preoperative overhydration followed by an intra-arterial bolus of 250 ml 14/1000 HCO3-, containing 1 g dexamethasone and 2500 I.U. sodium heparin, injected into the femoral artery before suturing the arteriotomy. This regimen was based on the measurement of myoglobin and glutathione levels respectively carried out in two subgroups of 25 patients. The results of experimental ischemia-reperfusion syndromes induced in animal using radical scavengers and membrane-protective compounds were also taken into consideration. Following experimental research on sheep, 5 patients in the second group with very severe ischemia due to aortic occlusion received local dialysis in the extracorporeal circulation using hemodialysis or hemofiltration techniques. Mortality was 6.3% in the first group and 5.4% in the second, while the amputation rate was 3% and 1.8% respectively. The overall incidence of the reperfusion syndrome was 3% in the 1st period and 1.8% in the second. Our findings confirm the protective effect of hyper-hydration, radical scavengers and dexamethasone in the ischemia reperfusion syndrome, and indicate that local hemodialysis is a useful adjunct in very severe ischemia.
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PMID:Ischemia: reperfusion syndrome of the lower limbs. 912 77

Under ischemic conditions O2 delivery is insufficient, and the cells convert to anaerobic metabolism with production of lactic acid. The protons formed in this process are to a large extent rapidly buffered inside the cell by proteins and HCO3-. Protons buffered by HCO3- form CO2 in the tissue. Since the blood supply during ischemia is minimal, CO2 is not transported away from the tissue and will reach tensions far above pCO2 found under aerobic conditions. Thus, measuring pCO2 can be used to detect ischemia in an organ. Gastrointestinal tonometry is based on the concept of CO2 accumulation during anaerobiosis. It has been customary to calculate so-called interstitial pH (pHi) by incorporating the measured pCO2 in the tonometer and the HCO3- in an arterial blood gas in the Henderson-Hasselbalch equation. However, this method has several weaknesses, and we recommend using the measured pCO2, or rather the difference between gastrointestinal and arterial pCO2. Experimental studies have shown that pCO2 electrodes sensitively detect the onset of ischemia also in solid organs. The accumulation of pCO2 coincides with the shift from supply-independent to supply-dependent oxygen consumption and correlates with other markers of ischemia. pCO2 measurement at organ level is a promising tool in the monitoring of organ ischemia.
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PMID:[CO2 pressure used in the diagnosis of ischemia]. 944 71

Long-term potentiation (LTP) is a long-lasting increase in synaptic strength induced by high frequency stimulation. LTP may participate in learning and memory formation. In many synaptic systems, LTP is dependent on intact function of N-methyl-D-aspartate (NMDA) receptors. NMDA receptors may be inhibited in different conditions involving also extracellular acidosis. A decrease in the extracellular pH accompanies many pathological states such as ischemia, hypoxia, and the CNS injury. The study was designed to determine whether comparable extracellular acid-base imbalances are able to interfere with the LTP induction. Hippocampal slices from adult rats were stimulated with high frequency stimulation (1 x 100 Hz/1 s) at Schaffer collateral-commissural synaptic system in the environment with different pH (6.7-7.8) and the field responses were recorded in CA1. Acidosis was achieved by supplying excessive CO2 or by HCO3-decrease in standard bicarbonate-containing buffer or by a direct acidification of the buffer containing Na-HEPES. Invariably, all forms of acidification suppressed the efficacy of normal, low frequency synaptic transmission and prevented the induction of LTP in a reversible manner; i.e., after reperfusion of the slices at pH 7.3 and restimulation, there was a return of synaptic transmission back to baseline, and a significant amount of LTP occurred. In contrast, alkalization to pH 7.8, although enhancing synaptic transmission efficacy, did not further increase the LTP magnitude compared to control environment with pH 7.3. The results suggest that extracellular acidosis associated with several pathological conditions in the CNS may significantly diminish the LTP induction, and thus negatively affect all physiological processes that utilize LTP.
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PMID:Extracellular acidosis and high levels of carbon dioxide suppress synaptic transmission and prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices. 951 84

Cu,Zn-superoxide dismutase (SOD1) acts as a peroxidase in the presence of H2O2 at high pH (pH > 9). The high pH species of H2O2, HO2-, was previously implicated as the reactive species. However, recent EPR studies of the enzyme performed in the physiological pH range 7.4-7.6 with the spin trap 5,5'-dimethyl-1-pyrolline-N-oxide attributed the intense EPR signal of 5, 5'-dimethyl-1-pyrolline-N-oxide-OH obtained from SOD1 and H2O2 to the peroxidase activity of the enzyme. The present study establishes that this intense signal is obtained only in the presence of bicarbonate. To explore the critical role of HCO3-, a comprehensive EPR investigation of the radical production and redox state of the active site copper was performed. The results indicate that HCO3- competes with other anions for the anion-binding site of SOD1 (Arg141) but does not bind directly to the copper. Structurally different anions that bind to Arg141 did not stimulate, but rather blocked, peroxidase function, ruling out an effect due to mere anion binding. However, the structurally similar anions HSeO3- and HSO3- mimic HCO3- in stimulating peroxidase function. These data suggest that HCO3- bound to Arg141 anchors the neutral H2O2 molecule at the active site copper, enabling its redox cleavage. Thus, SOD1 acquires peroxidase activity at physiological pH only in the presence of HCO3- or structurally similar anions. Alterations in pH that shift the HCO3-/CO2 equilibrium as occur in disease processes such as ischemia, sepsis, or shock would modulate the peroxidase function of SOD1.
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PMID:Bicarbonate is required for the peroxidase function of Cu, Zn-superoxide dismutase at physiological pH. 988 Apr 90

Inhibitors of carbonic anhydrase activity have been found to increase blood and organ PCO2 and to increase blood flow (BF) in individual organs. To determine whether carbonic anhydrase inhibition coordinately induces an increase in BF in several organs, we assayed the effect of the carbonic anhydrase inhibitor, acetazolamide (AZ), on BF in rabbit organs using the colored microsphere (CM) assay. Eight female white rabbits were anesthetized with ketamine and urethane, and administered three sequential doses of 4 mg/kg AZ. After each dose, the rabbits were injected with 9 x 10(5) CMs of different colors, and arterial blood was collected. We found that AZ had no effect on blood pressure, body temperature, hemoglobin concentration, or PaCO2. In contrast, 12 mg/kg AZ significantly increased PaO2 and significantly decreased base excess. When we measured organ BF, we observed, in response to 12 mg/kg AZ, an 82% increase in brain BF and a 55% increase in kidney BF, but no change in BF of the liver, stomach wall, or abdominal muscle. These findings suggest that the inhibition of carbonic anhydrase activity by AZ, which decreases the rate of CO2 conversion to HCO3-, causes the retention of CO2 in tissues and organs, and thus increases BF in specific organs. Administration of carbonic anhydrase inhibitors, such as AZ, may increase BF to the brain and kidney without reducing PaO2, thereby increasing the supply of oxygen in conditions involving hypoxia such as ischemia and shock.
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PMID:Acetazolamide-induced increase in blood flow to rabbit organs is confirmed using colored microspheres. 998 39

This study was intended to compare the cardiac consequences of ischemia/reperfusion and amiloride treatment in immature (2-3 wk), juvenile (4-6 wk), and adult (3-5 mo) rats using an isolated, perfused heart model. Male immature, juvenile, and adult rats were anticoagulated and anesthetized. Hearts were harvested and coronary arteries were perfused on a Langendorff apparatus via retrograde perfusion of the aorta at a constant coronary flow (initially determined by perfusing the heart at 50 mm Hg perfusion pressure) with oxygenated Krebs-Henseleit-Bicarbonate (KHB) solution. Left ventricular peak systolic (LVPSP) and end diastolic (LVEDP) pressures were measured via a balloon-tipped catheter placed in the left ventricle through the mitral valve. Following a 20-30 min stabilization period, hearts underwent 30 min of normothermic ischemia and were then reperfused with Krebs-Henseleit-Bicarbonate alone for 30 min, or Krebs-Henseleit-Bicarbonate containing 500 microM amiloride for 5 min followed by Krebs-Henseleit-Bicarbonate alone for 25 min (n = 6/age group). Left ventricular generated pressure was calculated (left ventricular peak systolic-left ventricular end diastolic) and used as a measure of ventricular function. All hearts demonstrated a decrease in generated pressure, respectively, from preischemic levels at 15 and 30 min of reperfusion, although this decrease was significantly less for the immature hearts. Ischemia/reperfusion injury was attenuated by amiloride in adult and juvenile hearts, whereas ischemia/reperfusion injury was worsened by amiloride in immature hearts. Although immature hearts were relatively resistant to ischemia/reperfusion injury compared with adult and juvenile hearts, the presence of amiloride during reperfusion resulted in more severe ventricular dysfunction in immature hearts. These data suggest a differential age-dependent mechanism of sarcolemmal ion exchange in response to ischemia/reperfusion.
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PMID:Effect of amiloride on age-dependent cardiac dysfunction after ischemia/reperfusion in the isolated, perfused rat heart. 1018 76

The consumption of red wine has been reported to impart a greater benefit in the prevention of coronary heart disease than the consumption of other alcoholic beverages. This beneficial effect is increasingly being attributed to certain antioxidants comprising the polyphenol fraction of red wine such as transresveratrol. In the present study, we investigated the potential cardioprotective effects of resveratrol in the face of ischemia reperfusion (I/R) injury. Isolated perfused working rat hearts after stabilization were perfused with Krebs-Henseleit Bicarbonate buffer (KHB) either in the presence or absence of transresveratrol (RVT) at a concentration of 10 microM for 15 min prior to subjecting them to 30 min of global ischemia followed by 2 h of reperfusion. Left ventricular functions were monitored at various timepoints throughout the reperfusion period to assess the extent of postischemic recovery in comparison with baseline values. Coronary perfusate samples were also collected to determine malonaldehyde (MDA) levels. The results demonstrated that RVT exhibited significant myocardial protection. This was evidenced by improved recovery of post-ischemic ventricular function including developed pressure and aortic flow as compared to the control group (KHB). Values for developed pressure in the RVT-treated group were significantly higher than those in the control group throughout the reperfusion period (71.09+/-4.88 mm Hg vs. 58.47+/-3.88 mm Hg, 68.87+/-5.07 mm Hg vs. 49.74+/-2.65 mm Hg and 51.67+/-3.95 mm Hg vs. 30.50+/-4.80 mm Hg at reperfusion timepoints R-15, R-60, and R-120, respectively). From R-30 onwards, aortic flow was markedly higher in the RVT treated group as compared with the control group, the differences being most significant at R-90 (32.45+/-2.19 ml/min vs. 19.83+/-1.62 ml/min) and R-120 (27.15+/-2.27 ml/min vs. 14.10+/-1.69 ml/min). In contrast to the KHB treated group, the RVT-treated group displayed significant reduction in MDA formation especially in the immediate early reperfusion period (63.71+/-8.19 pM/ml vs. 130.86+/-4.76 pM/ml, 63.84+/-15.62 pM/ml vs. 156.99+/-18.93 pM/ml, 71.29+/-2.80 pM/ml vs. 129.5+/-10.30 pM/ml and 56.25+/-5.79 pM/ml vs. 127.99+/-3.50 pM/ml at timepoints R-1, R-3, R-5, and R-7, respectively) indicating a reduction in I/R injury related oxidative stress. Infarct size was markedly reduced in the RVT group when compared with the control group (10.57+/-0.35% vs. 36.27+/-5.28%). In vitro studies revealed RVT to be a potent scavenger of peroxyl radicals suggestive of a probable mechanism involved in the protective ability of RVT. The results of this study indicate that resveratrol possesses cardioprotective effects which may be attributed to its peroxyl radical scavenging activity.
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PMID:The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. 1044 32

Acute traumatic or ischemic cerebral lesions are associated with tissue acidosis leading to cytotoxic brain edema, predominantly affecting astrocytes. Glial swelling from acidosis is believed to be the attempt of cells to maintain a physiological intracellular pH (pHi). However, this concept, potentially important for the development of new treatment strategies for cytotoxic brain edema, has not been validated experimentally. In the present study, cell volume and pHi of astrocytes were measured simultaneously in vitro. Exposure of suspended astrocytes to levels of acidosis found in vivo during ischemia and trauma (pH 6.8-6.2) led to a maximal increase in cell volume of 121.2% after 60 min (n = 5, p < 0.05) and to immediate intracellular acidification close to extracellular levels (pH 6.2, n = 5, p < 0.05). Inhibition of membrane transporters responsible for pHi regulation (0.1 mM amiloride for the Na+/H+ antiporter or 1 mM SITS for HCO3- -dependent transporters) inhibited cell swelling from acidosis but did not affect the profound intracellular acidification. In addition, acidosis-induced cell swelling and intracellular acidification were partly prevented by the addition of ZnCl2 (0.1 mM), an inhibitor of selective proton channels not yet described in astrocytes (n = 5, p < 0.05). In conclusion, these data demonstrate that glial swelling from acidosis is not a cellular response to defend the normal pHi, as had been thought. If these results obtained in vitro are transferable to in vivo conditions, the development of blood-brain barrier-permeable agents for the inhibition of acidosis-induced cytotoxic edema might be therapeutically useful, since they do not enhance intracellular acidosis and thus cell damage.
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PMID:Effect of lactacidosis on cell volume and intracellular pH of astrocytes. 1052 Nov 42

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.
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PMID:Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts. 1064 13

We investigated the effect of a newly synthesized compound, SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid] on Na+/H+ or Na+/Ca2+ exchange activity in rat cardiomyocytes, and on radioligand binding with several channels or receptors in membrane preparations, and ischemia/reperfusion injury in isolated perfused rat hearts. In myocytes, SM-20550 concentration-dependently inhibited the recovery from acidosis induced by an NH4Cl prepulse in HCO3(-)-free solution. Its IC50 was 10(-8) M, which was 10 times lower than that of ethylisopropyl amiloride (EIPA). SM-20550 (10(-6) M) did not affect the Na+-dependent Ca2+ influx (Na+/Ca2+ exchange activity) in cardiomyocytes. In the radioligand binding assay, SM-20550 did not have affinity for K+ channel, beta-adrenoceptor, adenosine, angiotensin, or endothelin receptors, and had low affinity for Na+ and Ca2+ channels and alpha-adrenoceptors, only at the concentrations of 10(-6)-10(-5) M. In perfused hearts exposed to 40 min of global ischemia and 20 min of reperfusion, SM-20550 (10(-8)-10(-7) M) significantly reduced the elevation of left ventricular end-diastolic pressure during reperfusion, improved the postischemic recovery of developed pressure, and prevented coronary perfusion pressure increase after reperfusion. Furthermore, SM-20550 reduced creatine phosphokinase release during reperfusion and prevented the abnormal gain of tissue Na+ and Ca2+ at the end of reperfusion. These results suggest that SM-20550 is a potent, highly specific Na+/H+ exchange inhibitor, which exerts a protective effect against myocardial ischemia/reperfusion injury. In addition, our data strongly support the hypothesis that Na+/H+ exchange plays an important role in the development of postischemic cardiac dysfunction, most likely by inducing Na+ and Ca2+ overload.
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PMID:SM-20550, a new Na+/H+ exchange inhibitor and its cardioprotective effect in ischemic/reperfused isolated rat hearts by preventing Ca2+-overload. 1083 18


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