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

By the systemic administration of diethyldithiocarbamate and iron into the rat, nitric oxide radicals produced in the brain during ischemia-hypoxia were trapped. The right hemisphere of the brain was then removed and frozen with liquid nitrogen. With use of recently developed electron paramagnetic resonance imaging instrumentation and techniques, three-dimensional imaging of the production of the nitric oxide radicals in several brains was performed. The results suggest that nitric oxide radicals were produced and trapped in the areas that are known to have high nitric oxide synthase activity, such as cortex, hippocampus, hypothalamus, amygdala, and substantia nigra. In this ischemia-hypoxia model, which did not interrupt the posterior circulation, the production and trapping of nitric oxide in the cerebellum were approximately 30% of those in the cerebrum.
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PMID:Three-dimensional imaging of nitric oxide production in the rat brain subjected to ischemia-hypoxia. 759 49

Ischemic preconditioning (PC) has been shown to limit ischemia- and reperfusion-induced arrhythmias. We wished to determine whether the antiarrhythmic effect of PC would be affected by inhibition of the L-arginine nitric oxide (NO) pathway in anesthetized rats. Ischemia and reperfusion were produced by occlusion and release of a snare around the left coronary artery in all rats. The effect of PC (three cycles of 2-min coronary artery occlusion and 5-min reperfusion) on development of reperfusion-induced arrhythmias after 5-min coronary artery occlusion was studied in 12 rats. In 24 other rats, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA 10 mg/kg, n = 12) or the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 12), was administered intravenously (i.v.) before PC. In control groups, solvent (n = 15), L-NAME (10 mg/kg i.v., n = 12), L-NMMA (10 mg/kg i.v., n = 12), or L-arginine (L-Arg 100 mg/kg i.v., n = 12) was administered to rats 5 min before coronary artery occlusion without PC. PC significantly reduced the incidence of ventricular premature beats (VPBs) from 100% in the non-PC solvent group to 17%, decreased the incidence of ventricular tachycardia (VT) from 93 to 8%, and abolished the incidence of reversible and irreversible ventricular fibrillation (RVF and IVF: 87 and 47% in the non-PC solvent group, respectively). L-NAME and L-NMMA did not significantly affect the protective effect of PC on reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does the antiarrhythmic effect of ischemic preconditioning in rats involve the L-arginine nitric oxide pathway? 759 18

Prior experiments on hypothermic ischemia/reperfusion have shown that (1) leukocytes have an important role in the injury resulting from hypothermic ischemia/reperfusion and (2) endothelial dysfunction with reduced release of nitric oxide occurs after hypothermic ischemia/reperfusion. L-Arginine is a nitric oxide precursor, and the effects of nitric oxide released from endothelial cells include vasorelaxation and inhibition of leukocyte adhesion to endothelium. The potential roles of an interaction between endothelial dysfunction and leukocyte-mediated injury were examined in neonatal hearts. Thirty-two isolated, blood-perfused neonatal lamb hearts were subjected to 2 hours of 10 degrees C cardioplegic ischemia. Group L-arginine received a 3 mmol/L dose of L-arginine during the first 20 minutes of reperfusion. In group leukocyte depletion, leukocytes were depleted (Sepacell filter) from the perfusate before reperfusion. In group L-arginine+leukocyte depletion, leukocytes were depleted and a 3 mmol/L dose of L-arginine was infused during early reperfusion. The control group had no intervention during reperfusion. At 30 minutes of reperfusion, left ventricular maximum developed pressure, positive maximum and negative maximum first derivative of left ventricular pressure (dP/dt), developed pressure at V10 (volume that produces a left ventricular endiastolic pressure of 10 mm Hg at baseline measurement), and dP/dt at V10 were measured. Coronary blood flow was continuously monitored and oxygen consumption was also measured to evaluate the metabolic recovery. In each heart, we also tested coronary vascular resistance response to the endothelium-dependent vasodilator acetylcholine 10(-7) mol/L and the endothelium-independent vasodilator trinitroglycerin 3 x 10(-5) mol/L to assess endothelial function. Results are given as mean percent recovery of baseline values +/- standard deviation. Group L-arginine+leukocyte depletion showed significantly greater recovery of left ventricular function than the other three groups, and groups L-arginine and leukocyte depletion also showed better recovery than the control group (positive maximum dP/dt: control group = 68.3% +/- 8.8%, group L-arginine = 88.8% +/- 3.8%, group L-arginine+leukocyte+leukocyte depletion = 100.6% +/- 8.7%, group leukocyte depletion = 79.3% +/- 8.1%; p < 0.05). Groups L-arginine and L-arginine+leukocyte depletion had higher postischemic coronary blood flow than other groups (control group = 133.0% +/- 31.6%, group L-arginine = 203.2% +/- 32.1%, group L-arginine+leukocyte depletion = 222.0% +/- 30.4%, group leukocyte depletion = 156.3% +/- 29.0%; p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Additive effects of L-arginine infusion and leukocyte depletion on recovery after hypothermic ischemia in neonatal lamb hearts. 760 41

The objective of this study was to assess the cardioprotective effect of the nitric oxide (.NO) donor, S-nitrosoglutathione (GSNO) and to investigate the mechanism of cardioprotection in a model of ischemia and reperfusion in isolated rat hearts. The role of .NO in myocardial protection was investigated by using nitronyl nitroxide as the .NO trap. Electron spin resonance spectroscopy was used to demonstrate that nitronyl nitroxide can trap .NO released from GSNO in a cardioplegic solution. .NO traps, oxyhemoglobin (4 mumol/l, n = 4) and nitronyl nitroxide (400 mumol/l, n = 5), inhibited the (2 mumol/l) GSNO-induced coronary vasodilation from the control value of 122% (n = 6) above base-line value to 73 and 60%, respectively. In the ischemia-reperfusion protocol, GSNO (20 mumol/l) was added to the cardioplegic solution during a 35-min ischemic arrest (n = 8). GSNO improved the functional recovery of ischemic hearts as compared to control (n = 6) as measured by the developed pressure (76 +/- 3 to 95 +/- 5% of base-line), rate pressure product (68 +/- 3 to 83 +/- 4% of base-line) and diastolic pressure (31 +/- 2 to 19 +/- 3 mm Hg). Reduction of coronary flow rate during reperfusion to control values in GSNO-treated hearts did not eliminate the improvement of functional recovery induced by GSNO. GSNO increased cyclic GMP production and slowed the accumulation of lactate (154 +/- 7 in control to 114 +/- 4 mumol/g dry wt.) and glucose-6-phosphate (3.66 +/- 0.19 in control to 2.18 +/- 0.10 mumol/g dry wt.) in myocardial tissue during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:S-nitrosoglutathione improves functional recovery in the isolated rat heart after cardioplegic ischemic arrest-evidence for a cardioprotective effect of nitric oxide. 761

The difference in end-products of the nitric oxide, i.e., nitrate-plus-nitrite, in the coronary arterial and venous blood was increased during coronary hypoperfusion of the canine heart (12.8 +/- 0.6 vs. 2.2 +/- 0.2 microM at the baseline). Norepinephrine from sympathetic nerve endings in the heart is released due to ischemic stress, however the relation of norepinephrine with nitric oxide is unknown during ischemia. Neither beta- or alpha 2-adrenoceptor antagonists attenuated the release of nitric oxide during coronary hypoperfusion. An intracoronary infusion of an alpha 1-adrenoceptor antagonist attenuated the release of nitric oxide during coronary hypoperfusion (5.3 +/- 0.4 microM), and the attenuation of alpha 1-adrenoceptor activity further decreased coronary blood flow during hypoperfusion. These findings suggest that alpha 1-adrenoceptor activity contributes to the mechanisms whereby nitric oxide is released from the ischemic myocardium.
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PMID:Roles of alpha 1-adrenoceptor activity in the release of nitric oxide during ischemia of the canine heart. 762 2

The hypothesis was tested that plasma from ischemic hindlimbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross clamping for 5 h after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 h in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10(-5) M) induced greater contraction in rings incubated in control vs. ischemic plasma, suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips incubated in ischemic or control plasma. Acetylcholine-induced nitrite release was significantly lower in ischemic vs. control plasma-incubated strips (8.6 +/- 2.7 vs. 28.2 +/- 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation to acetylcholine in ischemic plasma-incubated rings was significantly increased by L-arginine but not by prior treatment of ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension.
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PMID:Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats. 763 55

N-Methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity may depend, in part, on the generation of nitric oxide (NO.) and superoxide anion (O2.-), which react to form peroxynitrite (OONO-). This form of neurotoxicity is thought to contribute to a final common pathway of injury in a wide variety of acute and chronic neurologic disorders, including focal ischemia, trauma, epilepsy, Huntington disease, Alzheimer disease, amyotrophic lateral scelerosis, AIDS dementia, and other neurodegenerative diseases. Here, we report that exposure of cortical neurons to relatively short durations or low concentrations of NMDA, S-nitrosocysteine, or 3-morpholinosydnonimine, which generate low levels of peroxynitrite, induces a delayed form of neurotoxicity predominated by apoptotic features. Pretreatment with superoxide dismutase and catalase to scavenge O2.- partially prevents the apoptotic process triggered by S-nitrosocysteine or 3-morpholinosydnonimine. In contrast, intense exposure to high concentrations of NMDA or peroxynitrite induces necrotic cell damage characterized by acute swelling and lysis, which cannot be ameliorated by superoxide dismutase and catalase. Thus, depending on the intensity of the initial insult, NMDA or nitric oxide/superoxide can result in either apoptotic or necrotic neuronal cell damage.
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PMID:Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. 763 61

We tested the hypotheses that maintaining the activity of nitric oxide by L-arginine infusion would counteract the release of an endogenous nitric oxide synthase inhibitor, improve survival, and decrease intraoperative hypertension after infrarenal aortic cross-clamp surgery. Hindlimb ischemia was generated by infrarenal aortic cross-clamping and tying of the left femoral artery for 5 hours in rats with bilateral femoral and sciatic nerves cut. Mean blood pressure significantly increased during the 5-hour ischemic period in ischemic rats (no drug treatment). Baroreceptor function was inhibited in ischemic rats assessed by intravenous dose response to phenylephrine and nitroprusside after 5 hours of ischemia, suggesting baroreceptor resetting. In ischemic rats infused with L-arginine the intraoperative hypertension was prevented during the 5-hour period, suggesting that this hypertension may be mediated by nitric oxide inhibition. The rates of survival and arrhythmias 2 hours after declamping were 50% in ischemic rats and 100% in ischemic rats treated with N omega-nitro-L-arginine (a nitric oxide synthase inhibitor) 10 minutes before declamping. In ischemic rats infused with L-arginine the survival rate was significantly increased to 100% and the arrhythmic rate was inhibited. We conclude that L-arginine prevents hypertension during cross-clamping and decreases the mortality rate and arrhythmias after declamping by maintaining nitric oxide synthesis. These results suggest that humoral factors released from the ischemic hindlimb may inhibit endogenous nitric oxide production, thus contributing to intraoperative hypertension, arrhythmias, and high mortality rate after aortic cross-clamp surgery.
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PMID:Stimulation of endogenous nitric oxide pathway by L-arginine reduces declamp mortality and attenuates hypertension associated with aortic cross-clamp-induced hindlimb ischemia in rats. 764 74

The effect of L-arginine, the precursor of nitric oxide, on ischemic dopamine release from the striatum was investigated in Mongolian gerbils subjected to bilateral carotid artery occlusion (15 min) alone or with reflow (2 h). Dopamine and its metabolites were measured in the striatal extracellular space dialysate after continuous perfusion (2 microliters/min) of artificial extracellular fluid in the presence or absence of 15 mmol/liter L- or D-arginine or 1 mmol/liter nitro-L-arginine. L-Arginine but not D-arginine increased the striatal content of dopamine in pre- and postischemia whereas it lowered the levels of dopamine and 3-methoxytyramine induced by ischemia. In contrast, nitro-L-arginine reduced the preischemic levels of dopamine and 3,4-dihydroxyphenyl-acetic acid, and had no effect on the ischemic release of dopamine. These findings indicate that L-arginine stereospecifically modified the ischemic release and metabolism of dopamine. The data also suggest that the basal level of nitric oxide is not involved in dopamine release during ischemia but may participate in regulating dopamine release under physiological conditions.
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PMID:Modulation of striatal dopamine release in cerebral ischemia by L-arginine. 765 86

We have previously proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. NO previously has been found to inhibit mitochondrial activity in other cell types. Accordingly, we sought to determine if cytokine-stimulated NO production inhibited cardiac myocyte mitochondrial activity. Treatment of neonatal rat cardiac myocytes with interleukin-beta (IL-1) resulted in the expression of mRNA for inducible NO synthase (iNOS) and stained positively for iNOS protein by immunohistochemistry. No iNOS staining was detected in untreated cells. IL-1 treatment resulted in significant nitrite levels vs control over 48 hrs (4.2 +/- 0.7 vs 0.3 +/- 0.2 nmol/1.25 x 10(5) cells, respectively) (n = 12) that was inhibited by 1mM NMA (0.3 +/- 0.2 nmoles; p < .01; n = 12). Mitochondrial activity was assessed by the MTT colorimetric assay using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and OD 570-630. Mitochondrial activity was significantly inhibited by IL-1 vs control cells (0.436 +/- 0.01 vs 0.608 +/- 0.03) and reversed by 1mM NMA (0.549 +/- 0.03) or removal of IL-1 (0.662 +/- 0.02) (p < .01; n = 12 for each). These data strongly suggest that cytokine-stimulated NO production by cardiac myocytes results in reversible inhibition of mitochondrial activity.
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PMID:Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. 765 17


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