UMLS:C0022116 - FACTA Search

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

Global myocardial ischemia and reperfusion injury play a major role in early postoperative graft dysfunction. In this study, the influence of nitric oxide (NO) on reperfusion injury and catecholamine sensitivity after ischemia was investigated in a heterotopic rat heart-transplantation model. After a 1-h ischemic preservation, reperfusion was started either after application of saline vehicle (control, n = 8) or nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 8) for inhibition of NO synthesis or NO-precursor L-arginine (L-Arg; 40 mg/kg, n = 8), or L-NAME plus L-Arg (n = 8), respectively. After 60 min of reperfusion, continuous dobutamine infusion (5 microg/kg/min) was started. Myocardial blood flow was assessed by the hydrogen-clearance method. An intraventricular balloon was used to measure pressure-volume relations: peak left ventricular pressure, the rate of pressure development (dP/dt), end-diastolic pressure, and isovolumic relaxation constant. Myocardial blood flow was significantly reduced after L-NAME and increased after L-Arg in comparison with control (p < 0.05). The L-NAME group showed decreased systolic and diastolic functional recovery in comparison with control. Simultaneous infusion of L-Arg and L-NAME reversed these effects. L-Arg alone led to a further improvement of cardiac functional recovery. Whereas myocardial blood flow remained unchanged in the L-NAME group with dobutamine infusion, it significantly increased in the control group (p < 0.05). L-Arg antagonized this effect of L-NAME. Dobutamine increased peak left ventricular pressure and dP/dt and shortened the isovolumic relaxation constant in all groups; however, the changes of systolic hemodynamic indices were significantly smaller in the L-NAME group (p < 0.05) and significantly higher in the L-Arg group (p < 0.05). These results indicate that (a) NO production within the graft during reperfusion has a significant beneficial effect on graft function, and (b) NO formation may play an important role in beta-adrenergic responses after heart transplantation.
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PMID:Effects of nitric oxide synthesis on reperfusion injury and catecholamine responsiveness in a heterotopic rat heart-transplantation model. 947 63

Cessation of blood flow during ischemia will decrease both distending and shear forces exerted on endothelium and may worsen ischemic lung injury by decreasing production of nitric oxide (NO), which influences vascular barrier function. We hypothesized that increased intravascular pressure (Piv) during ventilated ischemia might maintain NO production by increasing endothelial stretch or shear forces, thereby attenuating ischemic lung injury. Injury was assessed by measuring the filtration coefficient (Kf) and the osmotic reflection coefficient for albumin (sigmaalb) after 3 h of ventilated (95% O2-5% CO2; expiratory pressure 3 mmHg) ischemia. Lungs were flushed with physiological salt solution, and then Piv was adjusted to achieve High Piv (mean 6.7 +/- 0.4 mmHg, n = 15) or Low Piv (mean 0.83 +/- 0.4 mmHg, n = 10). NG-nitro-L-arginine methyl ester (L-NAME; 10(-5) M, n = 10), NG-nitro-D-arginine methyl ester (D-NAME; 10(-5) M, n = 11), or L-NAME (10(-5) M)+L-arginine (5 x 10(-4) M, n = 6) was added at the start of ischemia in three additional groups of lungs with High Piv. High Piv attenuated ischemic injury compared with Low Piv (sigmaalb 0.67 +/- 0.04 vs. 0. 35 +/- 0.04, P < 0.05). The protective effect of High Piv was abolished by L-NAME (sigmaalb 0.37 +/- 0.04, P < 0.05) but not by D-NAME (sigmaalb 0.63 +/- 0.07). The effects of L-NAME were overcome by an excess of L-arginine (sigmaalb 0.56 +/- 0.05, P < 0.05). Kf did not differ significantly among groups. These results suggest that Piv modulates ischemia-induced barrier dysfunction in the lung, and these effects may be mediated by NO.
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PMID:Protective effects of intravascular pressure and nitric oxide in ischemic lung injury. 948 Sep 36

Because there are increasing evidences that nitric oxide (NO) plays important roles in ischemia-reperfusion injury in several systems, we investigated the role of NO in ischemia-reperfusion injury of the rat urinary bladder. Rat abdominal aorta was clamped with a small clip to induce ischemia-reperfusion injury in the rat bladder dome. In functional studies, contractile responses to carbachol were cumulatively measured after the urinary bladder was treated with various duration (0, 30, 60, and 90 min) of ischemia. The injury of rat bladder functioning was dependent on ischemic periods. Significant decreases in the Emax (maximum contractile response) values were observed in the bladder subjected to 60 or 90 min ischemia. Furthermore, the subsequent 30 min reperfusion caused additional damages of the contractile response in bladder muscles. To investigate the role of NO in the ischemia (30 min)-reperfusion (30 min) injury, NG-nitro-L-arginine methylester (L-NAME) was injected intraperitoneally 30 min before the ischemia. Treatment of L-NAME (30 and 100 mg/kg) partly but significantly prevented the reduction contractile responses to carbachol of the rat bladder dome. In histological studies, the ischemia-reperfusion caused infiltration of leukocytes and rupture of microcirculation in the regions of submucosa and smooth muscle without a corresponding sloughing of mucosal cells. The histological damages were also prevented by treatment with L-NAME. Therefore, these data suggested that ischemia-reperfusion of the urinary bladder may result in dysfunction of the contractile response to autonomic nervous system and that nitric oxide may act as a cell/tissue damaging agent in ischemia-reperfusion injury.
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PMID:Effect of ischemia-reperfusion on contractile function of rat urinary bladder: possible role of nitric oxide. 951 63

Recently we developed a model of cyclosporine nephropathy in rats characterized by tubulointerstitial (TI) injury, macrophage infiltration, and progressive interstitial fibrosis [1, 2]. To determine if the TI injury accompanying cyclosporine A (CsA) nephropathy was associated with accelerated apoptosis and ischemia, we treated rats for five weeks with CsA with or without losartan (to block angiotensin II type 1 receptor), or hydralazine/furosemide (H/F) (protocol #1). In protocol #2, rats received CsA with or without L-NAME (to block nitric oxide) or L-arginine (to provide a precursor to nitric oxide formation). Cyclosporine A treated rats had increased apoptosis of tubular and interstitial cells documented by PAS, propidium iodide staining, TUNEL assay, and electron microscopy compared to vehicle treated controls. Macrophages containing apoptotic cells could be confirmed by TUNEL/ED-1 doublestaining and colocalized in areas of TI injury. Animals treated with CsA + losartan had a statistically significant decrease in apoptosis (TUNEL + cells/mm2) when compared to CsA treated animals (6.0 vs. 19.9, P < or = 0.0001). The decrease in apoptosis in the CsA + H/F group was not statistically significant. Animals treated with CsA + L-NAME had a statistically significant increase in apoptosis compared to the CsA treated animals (12.3 vs. 6.4, P = 0.001). L-arginine administration with CsA resulted in a decrease in tubulointerstitial apoptosis versus CsA treated animals, however, this did not reach statistical significance. The addition of L-arginine did result in a significant reduction in interstitial fibrosis (P < 0.0001). Regression analysis revealed a significant correlation between apoptosis and interstitial fibrosis in both protocols. (CsA vs. CsA + losartan r = 0.63, P < 0.0001; CsA vs. CsA + L-NAME r = 0.83, P < 0.0001). We conclude that CsA nephropathy is associated with a marked increase in apoptosis of tubular and interstitial cells. Cyclosporine A induced apoptosis is partially mediated by angiotensin II and nitric oxide inhibition, suggesting a role for renal ischemia in this process, and CsA induced apoptosis correlates with interstitial fibrosis.
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PMID:Accelerated apoptosis characterizes cyclosporine-associated interstitial fibrosis. 955 96

Neutrophil activation and oxygen-derived free radical formation have been implicated in cardiac ischemia-reperfusion injury. To elucidate the mechanism of ischemia-reperfusion injury, we thus determined the effect of the nitric oxide (NO) precursor L-arginine on the free radical injury of cultured cardiomyocytes which were obtained from patients undergoing corrective surgery for tetralogy of Fallot. Free radicals were generated from hypoxanthine via xanthine oxidase, and the cellular changes were determined microscopically. All concentrations of L-arginine (0.5 to 3 mM) prolonged the myocyte survival time compared to the control group, with 0.5 mM L-arginine increasing the survival time to the greatest extent. Cellular susceptibility to free radical injury was the lowest with 0.5 mM L-arginine. Further experiments were performed with 0.5 mM L-arginine plus 100 mM or 1000 mM of the NO synthase (NOS) inhibitor NG-nitro-L-arginine methylester (L-NAME) to determine whether or not the effects of L-arginine are mediated through the NO pathway. The survival time for the cells treated with a concentration of L-NAME was shorter than for the cells treated with 0.5 mM L-arginine alone. These results suggest that L-arginine acts through the NO-dependent pathway. In conclusion, our findings thus confirmed the quenching effects of NO on free radical injury in cultured cardiomyocytes.
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PMID:Quenching the effects of L-arginine on free radical injury in cultured cardiomyocytes. 959 Jul 1

The purpose of this study was to investigate the mechanisms by which a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), is neuroprotective in the hyperglycemic rat model of 2 h of transient middle cerebral artery occlusion followed by 2 h of reperfusion (MCAO/R). The salicylate trapping method was used in conjunction with a microdialysis technique to continuously estimate hydroxyl radical (.OH) formation by measurement of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Extracellular excitatory amino acids (EAAs) were detected from the same microdialysis samples. Magnetic resonance imaging (MRI) techniques were used to measure neuronal and cerebrovascular injury. The magnitude of EAA release correlated with the levels of the .OH adducts. Treatment with L-NAME (3 mg/kg, i.p.) 1 min before MCAO, and again 1 min before reperfusion, reduced the levels of DHBA by 46. 4% and glutamate by 50.5% in the hyperglycemic rats compared to untreated hyperglycemic controls. MRI indicated that L-NAME reduced the no-reflow zone and the cytotoxic lesion volume to 22.5% and 21. 0%, respectively, that of hyperglycemic controls. Co-treatment with the nitric oxide (NO) donor L-arginine completely eliminated the protective effects of l-NAME with respect to .OH and EAA levels as well as MRI lesion volume. Our data suggest that hyperglycemic MCAO/R results in excessive glutamate excitotoxicity, leading to enhanced generation of .OH via a NO-mediated mechanism, in turn resulting in severe ischemia/reperfusion brain injury.
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PMID:Effect of nitric oxide synthase inhibitor on a hyperglycemic rat model of reversible focal ischemia: detection of excitatory amino acids release and hydroxyl radical formation. 959 67

The age-dependent responses of the mesenteric vasculature to ischemia-reperfusion (I/R) were compared in 2-mo-old and 2-yr-old rats. Measurements were made of leukocyte adherence, albumin leakage, and oxidative stress in postcapillary venules. In young rats I/R induced an increase in leukocyte adherence and albumin leakage, but in aged rats I/R induced an increase in albumin leakage without an increase in leukocyte adherence. Furthermore, I/R-induced oxidative stress was higher in the aged rats than in the young rats. To investigate whether the age-associated oxidative stress is related to a decrease in the role of nitric oxide, NG-nitro-L-arginine methyl ester (L-NAME) was superfused onto the mesentery of young and aged rats. L-NAME induced an increase in postcapillary protein leakage only in young rats; however, arteriolar constriction induced by L-NAME occurred in both age groups. These results suggest that different mechanisms contribute to the inflammatory responses and microvascular dysfunction elicited by I/R in young and aged rats.
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PMID:Age-dependent responses of the mesenteric vasculature to ischemia-reperfusion. 961 57

This study was undertaken to determine the extent to which nitric oxide (NO) mechanisms are involved in cerebral hyperemia following global brain ischemia. The vertebral arteries were cauterized through the first alar foramina in anesthetized male Sprague-Dawley rats and followed by 20-min occlusion of the common carotid arteries. Blood flow from the parietal cerebral cortex was measured using laser-Doppler flowmetry. In saline-treated animals, carotid occlusion reduced cerebral blood flow by approximately 95% with a maximal hyperemia of about 400% observed after 15 min of reperfusion. Pre-treatment with the nonspecific NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester; 2, 10 and 50 mg kg(-1)), produced dose-related depression of post-ischemic hyperemia, whereas D-NAME (10 mg kg(-1)) was inactive. Pre-treatment with L-arginine (300 mg kg(-1), i.v.) prevented L-NAME attenuation of cerebral hyperemia. The selective neuronal NO synthase inhibitor, 7-nitroindazole (30 mg kg(-1)), was without significant depressant effect. These results suggest that NO (largely from vascular endothelium) is instrumental in development of post-ischemic cerebral hyperemia.
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PMID:Role of nitric oxide in post-ischemic cerebral hyperemia in anesthetized rats. 965 86

Intraspinal injection of the nonspecific inhibitor of nitric oxide synthase N-nitro-L-arginine methyl ester (L-NAME) results in a dose-dependent loss of neurons in the rat spinal cord. This effect is thought to result from a reduction in basal levels of nitric oxide (NO), thereby producing an ischemic reaction secondary to vasoconstriction and reduced spinal cord blood flow (SCBF). An important component of this ischemic reaction is the release of excitatory amino acids and the initiation of an excitotoxic cascade. In the present study, microinjections of adenosine A1 and A2 receptor agonists were made in the spinal cord to evaluate the neuroprotective effects of these drugs against neuronal loss produced by L-NAME. Animals were divided into six groups based on the composition of injected solutions: (a) L-NAME; (b) L-NAME + N6-cyclopentyladenosine (CPA, A1 agonist); (c) L-NAME + 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA, A2 agonist); (d) L-NAME + CPA + CPCA; (e) N-methyl D-aspartate (NMDA); and (f) NMDA + CPA. Injections of L-NAME or NMDA produced a unilateral loss of spinal neurons, a local inflammatory response, and darkly stained pyknotic nuclei surrounding the area of neuronal loss. CPA and CPCA significantly reduced the area of L-NAME-induced neuronal loss, and a synergistic effect was observed when ineffective doses of these agonists were co-injected with L-NAME. The excitotoxic effects of NMDA were not affected by CPA. The results have shown that A1 and A2 receptor agonists provide significant neuroprotection against L-NAME induced neuronal loss, presumably by inhibiting ischemia induced release of excitatory amino acids (A1 agonist), or by restoring SCBF secondary to vasodilation (A2 agonist). It is suggested by these results that the intraspinal injection of L-NAME is an effective model to study the pathological consequences of vasoconstriction, reduced SCBF, and ischemia secondary to decreased NO production in the rat spinal cord. Finally, the results provide support for the continued investigation of specific adenosine agonists as therapeutic agents directed against the ischemic and excitotoxic components of spinal injury.
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PMID:Intraspinal injection of adenosine agonists protect against L-NAME induced neuronal loss in the rat. 967 51

This study was performed to examine the roles of body temperature, NMDA receptors and nitric oxide (NO) synthase in post-ischemic retinal injury in rats. Cell loss in the ganglion cell layer and thinning of the inner plexiform layer were observed 7 days after ischemia. Cell loss in the ganglion cell layer but not thinning of the inner plexiform layer was reduced by hypothermia during ischemia. Intravenous injection of dizocilpine (MK-801) or Nomega-nitro-L-arginine methyl ester (L-NAME) prior to ischemia ameliorated retinal injury. These results suggest that activation of NO synthase following NMDA receptor stimulation is involved in ischemia-induced retinal injury.
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PMID:Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina. 968 14

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