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)

1. Glutamate (Glu) uptake in neurons and astrocytes is essential to prevent the persistence of excitotoxic levels of Glu in the synaptic cleft. 2. We investigated the effect of oxidative stress, which is also involved in ischemia-reperfusion, on the Glu transporter in isolated rat retinal cells. 3. Hydrogen peroxide (H2O2 3-300 microM) decreases the Na+-dependent Glu uptake. This effect is not related to a free radical production and is partly reversed by reducing agents, suggesting a transporter modulation by a redox-related event.
Gen Pharmacol 1998 Mar
PMID:Free radicals and glutamate uptake in the retina. 951 79

1. Taurine has recently been known to protect against ischemia and heart failure. Taurine possesses plenty of actions on the ion channels and transports, but is very non-specific. 2. Taurine may directly and indirectly help to regulate the [Ca]i level by modulating the activity of the voltage-dependent Ca2+ channels (also dependent on [Ca]i/[Ca]o), by regulation of Na+ channels, and secondly via Na-Ca exchange and Na(+)-taurine cotransport. 3. Taurine can prevent the Ca2+ ([Ca]o or [Ca]i)-induced cardiac functions. 4. Therefore, it seems possible that taurine could exert the potent cardioprotective actions even under the condition of low [Ca]i levels as well as under the Ca2+ overload condition. 5. The electrophysiological actions of taurine on cardiomyocytes, smooth muscle cells, and neurons from recent studies are summarized.
Gen Pharmacol 1998 Apr
PMID:Review of some actions of taurine on ion channels of cardiac muscle cells and others. 952 60

1. Ranolazine shifts ATP production away from fatty acid oxidation toward glucose oxidation. 2. Because more oxygen is required to phosphorylate a given amount of ATP during fatty acid oxidation than during carbohydrate oxidation, the ranolazine-induced shift in substrate selection reduces the cell's demand for oxygen without decreasing its ability to do work. The shift also maintains coupling of glycolysis to glucose oxidation during ischemia, thus reducing tissue acidosis. 3. This unique, non-hemodynamic mechanism offers the potential to treat angina without reducing blood pressure, heart rate or myocardial contractility. 4. At least three double-blind, randomized, placebo-controlled clinical trials have yielded data consistent with this hypothesis.
Gen Pharmacol 1998 May
PMID:Ranolazine: a novel metabolic modulator for the treatment of angina. 955 12

1. The review summarizes the most important data known so far on chemistry, pharmacodynamics, toxicology and clinics of the investigational agent, pyridoindole stobadine. 2. Stobadine was shown to be able to scavenge hydroxyl, peroxyl and alkoxyl radicals, to quench singlet oxygen, to repair oxidized amino acids and to preserve oxidation of SH groups by one-electron donation. These effects originated from its ability to form a stable nitrogen-centered radical on indole nitrogen. Consequently, it was able to diminish lipid peroxidation and protein impairment under oxidative stress. 3. In various in vitro and in vivo animal models, stobadine was shown to diminish the impairment of the myocardium induced by mechanisms involving reactive oxygen species (e.g., myocardial infarction, hypoxia/ reoxygenation, catecholamine overexposure). 4. The neuroprotective effect of stobadine was demonstrated in a series of in vivo and in vitro models (brain in situ, brain slices, spinal cord, autonomic ganglia, etc.) during ischemia/reperfusion and hypoxia/ reoxygenation or in the presence of chemical systems generating free oxygen radicals, and so forth. Stobadine improved animal survival rate and synaptic transmission recovery, maintained SH tissue level and diminished lipid peroxidation as well as impairment of Ca-sequestering intracellular systems. 5. Oxidation of low-density lipoproteins (LDLs), which plays a major role in the development of atherosclerosis, was decreased by stobadine in vitro. Both lipid and protein (apo B) components of LDL were protected against Cu(2+)-induced oxidation by this agent. 6. Stobadine proved to be an effective protectant in models of free radical pathology in vivo, such as cyclophosphamide-, MNNG- or 60Co-induced mutagenesis and alloxan-induced hyperglycemia. 7. Besides other remarkable pharmacodynamic effects, stobadine exerts antidysrhythmic, local anesthetic, alpha-adrenolytic, antihistaminic, myorelaxant and antiulcerogenic actions. 8. Pharmacokinetic analyses demonstrated that stobadine was readily absorbed from the gastrointestinal tract. Thanks to its balanced lipo-hydrophilic properties, it was distributed over both water and lipid phases in biological tissues. It was shown to easily penetrate the blood-brain barrier. 9. Acute, subchronic and chronic toxicity studies in several animal species, as well as numerous analyses of embryotoxicity, teratogenicity, mutagenicity and genotoxicity, revealed only a negligible toxic potential of this agent. 10. Phase-one clinical study demonstrated safety of the compound. Only slight side effects--namely, a slight hypotension and a slight sedative effect--were observed subsequent to the highest dose used. In phase-two clinical study, the patients with angina pectoris treated for 4 weeks with stobadine showed a significant decrease in the frequency of anginal attacks, in the number of self-administrations of sublingual nitroglycerine and in plasma lipoprotein, cholesterol and triglyceride levels. A slight decrease in systolic and diastolic blood pressure also was observed. 11. It is suggested that stobadine may be considered a contribution to the search for new effective cardio- and neuroprotectants based on antioxidant or free radical scavenging mechanisms of action.
Gen Pharmacol 1998 May
PMID:Antioxidant and pharmacodynamic effects of pyridoindole stobadine. 955 11

1. ATP-sensitive potassium (KATP) channel openers shorten cardiac ventricular muscle action potential duration (APD), reduce resting and developed contractile force, and have been shown to provide cardioprotection when given before, during, and after either short-term ischemia or long-term hypothermia. The authors' aim was to determine the concentration-dependent effect of the potent KATP channel opener bimakalim on transmembrane action potential changes induced by mild (27 degrees C) and moderate (20 degrees C) hypothermia in isolated guinea pig ventricular muscle. 2. Conventional microelectrode techniques were used to record action potentials (APs) in single myocytes during normothermia (37 degrees C) and hypothermia in the presence and absence of 0.1 to 30 mumol.l-1 bimakalim. 3. Hypothermia alone increased APD and depolarized the diastolic membrane potential (DMP): APD90 = 141.7 +/- 7.0 msec and DMP -86.2 +/- 1.4 mV (n = 6) at 37 degrees C versus 235.7 +/- 7.8 msec and -75.6 +/- 1.0 mV at 20 degrees C (n = 7). At 37 degrees C, bimakalim (0.1-10 mumol.l-1) shortened APD in a concentration-dependent fashion. 4. APD90 was markedly reduced from 141.7 +/- 7.0 msec without bimakalim to 9.5 +/- 2.6 msec with 10 mumol.l-1 bimakalim (n = 6); this effect was blocked by glibenclamide. DMP was hyperpolarized by bimakalim. More bimakalim was required to shorten APs during mild and moderate hypothermia. The 50% effective concentration (EC50) of bimakalim required to maximally shorten APD90 was 0.96 +/- 0.10 mumol.l-1 at 37 degrees C; this increased to 3.96 +/- 0.24 mumol.l-1 at 27 degrees C, and to 12.34 +/- 0.72 mumol.l-1 at 20 degrees C. Relative to hypothermia-induced depolarization, bimakalim hyperpolarized DMP toward drug-free values obtained at 37 degrees C. 5. These results indicate that hypothermia shifts the bimakalim concentration APD90 response curve to the right such that 13 times more bimakalim is required at 20 degrees C shorten APD by the same amount as at 37 degrees C. Bimakalim also reverses hypothermia-induced AP lengthening and tends to reverse the hypothermia-induced decrease in DMP. 6. These findings aid in our understanding of the cardioprotective effects of KATP channel openers during hypothermia.
Gen Pharmacol 1998 Jul
PMID:Reversal of hypothermia-induced action potential lengthening by the KATP channel agonist bimakalim in isolated guinea pig ventricular muscle. 959 90

1. The aim of this study was to investigate the effects of enalapril maleate on ischemia-reperfusion injury of the myocardium, after cardioplegic arrest in isolated guinea pig hearts, in a modified Langendorff model. 2. Animals were subjected to 90 min of normothermic global ischemia, followed by 30 min of reperfusion. Cardioplegic arrest was achieved by administering St. Thomas Hospital cardioplegic solution (STHCS). 3. The hearts were randomly allocated into four groups (n=8 in each group). The first group was utilized as control. In the second group, oral pretreatment was made (0.2 mg/kg enalapril maleat was given twice a day for 10 days). In the third group, enalapril maleat (1 micromol/l) was added to STHCS. In the fourth group, hearts were arrested with enalapril maleat-enriched STHCS, and enalapril maleat-enriched (1 micromol/l) Krebs-Henseleit solution was applied during the reperfusion period. 4. Although the study groups showed better recovery of contractility than did the control group, in the last group, the hearts had the best recovery of left ventricular systolic function, where dp/dt maximum was 89.7+/-6.9% of the preischemic values. Group 1, group 2 and group 3 achieved 44.2+/-4.5%, 79.4+/-5.8% and 68.1+/-6.7% of their preischemic dp/dt values. A similar observation was found for left ventricular developed pressure (LVDP); LVDP values were 52.4+/-2.1% (in group 1), 79.6+/-2.8% (in group 2), 72.8+/-4.6% (in group 3) and 86.7+/-5.8% (in group 4) of control after reperfusion. Creatine kinase leakage was significantly lower and postischemic coronary flows were significantly higher in group 4. 5. We concluded that usage of enalapril maleat in the reperfusion period was more effective for improving myocardial recovery after cardioplegic arrest. The additional protective effects of enalapril maleat not only were by angiotensin-converting-enzyme-inhibition-dependent coronary vasodilation and thiol-dependent limitation of oxidative injury, but could also be related to an oxygen-free-radical-scavenging effect.
Gen Pharmacol 1998 Aug
PMID:Attenuation of ischemia--reperfusion injury by enalapril maleat. 968 60

1. We measured redox systems in resting and activated rat peritoneal mast cells under anoxia by using the redox metabolism of free doxyl stearic acid (5DS) and phosphatidylcholine with two 5DS molecules esterified to the glycerol (di5DSPC). 2. In the absence of oxygen, 5DS and di5DSPC were reduced to the corresponding hydroxylamines by resting mast cells, with apparent first-order kinetics of 0.085 and 0.078/min, respectively. 3. The activation of mast cells induced by compound 48/80 and bradykinin did not affect the rates of reduction of the nitroxides, and therefore the activation appeared not to be closely coupled to the redox system of these cells; this finding implies that ischemia is unlikely to affect histamine release from mast cells. 4. The oxidation of the nitroxides by the mast cells was very fast and may be nonenzymatic. 5. We concluded that nitroxides can be useful probes of redox metabolism in the mast cells but, because the characteristics of the cellular reduction-reoxidation systems differed from that of other cells, the use of this approach in other cells will require careful characterization of the redox metabolism of nitroxides in those cells.
Gen Pharmacol 1998 Oct
PMID:Characterization of redox activity in resting and activated mast cells by reduction and reoxidation of lipophilic nitroxides. 979 26

1. The effects of (-)-(S)-4-(3,4-dihydroxyphenyl)- 1,2,3,4-tetrahydroisoquinoline-7,8-diol monohydrochloride monohydrate (YM435), a dopamine DA1 receptor agonist, were evaluated in a canine model of ischemic acute renal failure (ARF). 2. ARF was induced by clamping the left renal artery for 1 hr and subsequent reperfusion of the left kidney in anesthetized uninephrectomized dogs. 3. After 1-hr complete renal artery occlusion, an intravenous infusion of either YM435 (0.3 microg/kg/ min) or 0.9% saline (vehicle) was begun and continued for 1 hr. 4. In the vehicle group, renal ischemia markedly decreased glomerular filtration rate, urine flow and urinary sodium excretion. The YM435 group was characterized by significant recoveries in glomerular filtration rate, urine flow, and urinary sodium excretion as compared with the vehicle group. 5. These results indicate that YM435 can facilitate recovery in glomerular filtration rate, urine flow, and urinary sodium excretion in a canine model of ARF induced by ischemia. YM435 may be useful in the preservation of renal function in ischemia-induced ARF.
Gen Pharmacol 1998 Nov
PMID:Effect of YM435, a dopamine DA1 receptor agonist, in a canine model of ischemic acute renal failure. 980 82

1. Cardioplegic solutions provide the opportunity to operate on a nonbeating heart and to protect the heart against ischemic injury during cardiac surgery. The components of these solutions are constantly being modified in an effort to find the optimal solution. We studied the effects of colloidal volume replacers such as dextran, HES and gelatin as an isocolloidoosmotic addition to St. Thomas Hospital cardioplegic solution in ischemia-reperfusion injury of isolated rat hearts. 2. In the control group, after a stabilization period of 20 min, the hearts were arrested with St. Thomas Hospital cardioplegic solution for 3 min, then subjected to 30 min of global ischemia. Hearts then were reperfused for 10 min. In the experimental groups, the protocol was the same, but either HES 200/0.5 (50 g/L), modified fluid gelatin (30 g/l) or dextran 70 (25 g/L) were added to the St. Thomas Hospital solution. 3. All hearts were compared for their preischemic and postischemic contractility, heart rate, contractility rate product, coronary flow, lactate dehydrogenase, creatine phosphokinase enzyme leakage and wet/dry weight ratio. 4. All groups had similar contractility (for control, HES, gelatin and dextran groups the values at minute 10 of reperfusion were 59+/-9, 56+/-11%, 61+/-14%, 49+/-14% of initial values [P>0.05, respectively]) and enzyme leakage (lactate dehydrogenase 4.1+/-1.0, 8.1+/-1.5, 5.8+/-1.4, 3.7+/-1.2 [P>0.05] and for creatine phosphokinase 3.9+/-2.5, 6.4+/-3.7, 5.5+/-1.3, 5.5+/-0.8, P>0.05] IU xmin(-1) x g dry tissue(-1) in the reperfusion period, respectively) results as compared with the control group. 5. The addition of isocolloidoosmotic colloids to the cardioplegic solution did not appear to enhance the effectiveness of the crystalloid St. Thomas Hospital cardioplegic solution. If a colloid is to be chosen as a plasma replacer or an additive to priming solution in the preoperative period, or during open-heart surgery, it should be modified fluid gelatin-for no sign of cardiodepression was determined with the use of this agent.
Gen Pharmacol 1999 Jan
PMID:No beneficial effects of isocolloidoosmotic synthetic colloid addition to St. Thomas Hospital cardioplegic solution in ischemia-reperfusion injury in isolated perfused rat hearts. 988 61

Oxygen and glucose are critical to support the survival and integrity of all smooth muscles. Hypoxia alone has been demonstrated to suppress the contractile response of corporal smooth muscle, and one might expect simultaneous deprivation of oxygen and glucose (in vitro model of ischemia) to exert more serious damage to corporal smooth muscle contraction. The effect of in vitro ischemia on the pharmacological responses of isolated rabbit corporal smooth muscle was correlated with the level of tissue lipid peroxidation. The effects of in vitro ischemia were as follows: (1) In vitro ischemia resulted in an 85% reduction in the contractile response to phenylephrine; (2) more than a 50% reduction in the activity of thapsigargin-sensitive calcium-activated ATPase activity of the microsomes (sarcoplasmic reticulum [SR]); (3) more than a fourfold increase in the tissue concentration of thiobarbituric acid reactive substances (TBARS) (level of lipid peroxidation). In conclusion, stimulation of lipid peroxidation in part may be responsible for the decrease in thapsigargin-sensitive calcium-activated ATPase activity of the SR (SERCA), and the correlated decrease in the contractile response to phenylephrine in response to ischemia.
Gen Pharmacol 1999 Mar
PMID:Correlation of calcium-activated ATPase activity, lipid peroxidation, and the contractile response of rabbit corporal smooth muscle treated with in vitro ischemia. 1021 90


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