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

The diameters of pial arterioles of mice were monitored in vivo with an image-splitting technique and television microscopy. Concentrations of leukotriene C4 as low as 10(-7) M constricted the arterioles. The leukotriene C4-D4 receptor blocker ICI 198615 (10(-8) M) inhibited the response. Endothelial injury by helium-neon laser/Evans blue technique eliminated the constriction and unmasked a slight but consistent relaxation that was not inhibited by 10(-8) M ICI 198615. Since leukotrienes are produced by the brain and enter the cerebrospinal fluid in ischemia, head trauma, and subarachnoid hemorrhage, the possibility that leukotrienes C4 and D4 contribute to decreases in cerebral blood flow during these conditions should be considered. However, the present data makes such a possibility far less likely because the endothelium is frequently injured in these conditions, and therefore the ability of leukotrienes to constrict vessels would be severely curtailed.
 ...
PMID:Leukotriene constriction of mouse pial arterioles in vivo is endothelium-dependent and receptor-mediated. 217 72

Coronary artery occlusion produces myocardial acidosis, which can be attenuated by propranolol or sotalol. The present study was undertaken to determine which beta adrenoceptors, beta-1 or beta-2, contribute to the ischemic myocardial acidosis. Dogs anesthetized with pentobarbital were used. In the first series of experiments, blood flow in the left anterior descending coronary artery was reduced by an occluder to about one-third of the original flow. Myocardial pH was measured by means of a micro pH electrode inserted into the left anterior descending coronary artery area at the depth of about 8 mm. The myocardial pH decreased from 7.44 to 7.55 to 6.73 to 6.89, 30 min after partial occlusion being the time immediately before an i.v. injection of drugs. Atenolol (1 mg/kg) attenuated significantly the decrease in myocardial pH that had been induced by partial occlusion, whereas IPS 339 (360 micrograms/kg) and ICI 118,551 (300 micrograms/kg) did not. The pH effect of atenolol was confirmed even in the paced heart. In the second series of experiments, the antagonistic action of these drugs on the isoproterenol-induced increase in heart rate and myocardial contractile force and the decrease in diastolic blood pressure was investigated. By this experiment, it was confirmed that atenolol has the beta-1 adrenoceptor antagonistic action, and the IPS 339 and ICI 118,551 have the beta-2 antagonistic action. These results suggest that the activation of beta-1 adrenoceptors contribute to the myocardial acidosis during ischemia.
 ...
PMID:Attenuation by atenolol of myocardial acidosis during ischemia in dogs: contribution of beta-1 adrenoceptors to myocardial acidosis. 285 88

The studies reported in this article provide evidence that several complex mechanisms are involved in the ability of dopexamine HCl (DPX) in preventing ischemia-reperfusion induced organ damage. In a canine model of hemorrhagic shock in which shed-blood was reinfused, DPX prevented deterioration in renal blood flow via an action on beta-2 and DA-1 receptors, whereas its ability to preserve tubular function was essentially due its agonistic effects on DA-1 receptors. In a different experimental model in anesthetized rats, acute generation of oxygen free radicals (OFR) via intravenous administration of Xanthine (X) followed by Xanthine Oxidase (XO) resulted in depression of circulation and death of more than 80% of the animals within the observation period of 120 min. Pretreatment of the rats with DPX significantly enhanced survival rate in a dose dependent manner to about 70%. Neither dobutamine nor prenalterol, which are beta-1 adrenoceptor agonists and like DPX, potent chronotropic and inotropic agents were effective in preventing OFR induced lethal toxicity. In a separate series, a selective DA-1 receptor agonist felodopam had no protective effect and a DA-1 receptor antagonist SCH-23390 failed to antagonize the salutary effects of DPX. In contrast, salbutamol, a selective beta-2 adrenoceptor agonist significantly promoted the survival rate facilitated by DPX and a selective beta-2 adrenoceptor antagonist, ICI-558,551 significantly attenuated the survival rate. These later studies suggest that unlike in hemorrhagic shock, the beta-2 adrenoceptor agonistic properties are critical in the ability of DPX to attenuate lethal toxicity and these effects could be related to prevention of lipid peroxidation induced by oxygen free radicals.
 ...
PMID:Efficacy and mechanisms of dopexamine in the prevention of ischemia-reperfusion induced organ damage: role of oxygen free radicals. 902 45

We used an isolated, blood-perfused rat lung model to evaluate the separate roles of ischemia and reperfusion time, the changes in pulmonary artery pressure (Ppa), and the circulating neutrophil number in mediating ischemia-reperfusion lung injury. Extravascular albumin accumulation was used to quantify changes in the permeability of the alveolar capillary membranes. In animals subjected to 30 and 45 min of ischemia without reperfusion, extravascular albumin accumulation was significantly higher than in controls subjected to continuous perfusion (P < 0.05). Albumin accumulation in animals subjected to 45 min of ischemia was greater compared with those undergoing 30 min of ischemia followed by 30 min of reperfusion (P < 0.05). In animals undergoing 45 min of ischemia followed by 30 min of reperfusion, a linear relationship was demonstrated between changes in Ppa and extravascular albumin accumulation. Reducing Ppa with a thromboxane antagonist (ICI-192605) and a smooth muscle relaxant (papaverine) produced, in both cases, a significant decrease in albumin extravasation (P < 0.05). No significant difference in extravascular albumin accumulation or change in Ppa was shown in neutrophil-depleted animals compared with nondepleted animals. We conclude that ischemia time contributes significantly to ischemia-reperfusion lung injury and that transient changes in Ppa after reperfusion exacerbate and injury in this model. This early injury demonstrated here was neutrophil dependent.
 ...
PMID:Ischemia-reperfusion lung injury: contribution of ischemia, neutrophils, and hydrostatic pressure. 925 39

A growing body of evidence supports the hypothesis that estrogens may be beneficial in Alzheimer's disease and other neurodegenerative processes. Less is known of their therapeutic potential in acute CNS insults. In this study, we assessed the effect of estrogens in three injury paradigms that may be relevant to CNS hemorrhage, trauma, and ischemia. Supraphysiologic concentrations of 17beta-estradiol, estrone, or equilin attenuated neuronal loss due to prolonged exposure to the pro-oxidant hemoglobin, with complete protection at 10 microM. Most of this effect persisted despite concomitant treatment with the antiestrogen ICI 182,780 or the protein synthesis inhibitor cycloheximide. In contrast, the non-estrogenic steroid methylprednisolone, which is currently in clinical use in spinal cord injury, reduced neuronal loss by only about 30%. High concentrations of equilin or estrone also attenuated the submaximal neuronal injury induced by 3.5-4.5 h exposure to the cytochrome oxidase inhibitor sodium azide, with near complete protection at 30 microM. Estrogens had a weaker and somewhat variable effect on pure excitotoxic injury, reducing neuronal loss due to 24 h kainate exposure by about half, and due to 24 h NMDA exposure by 15-65%; similar neuroprotection was provided by the antioxidant 21-aminosteroid U74500A. These results suggest that estrogens may be beneficial in acute CNS injuries associated with oxidative and excitotoxic stress. Investigation of high dose estrogen therapy in in vivo models of CNS hemorrhage, trauma, and ischemia is warranted.
 ...
PMID:Estrogens attenuate neuronal injury due to hemoglobin, chemical hypoxia, and excitatory amino acids in murine cortical cultures. 929 2

In vivo pre-treatment with the opioid receptor antagonist D,L-naloxone completely eliminated the reperfusion-induced creatine kinase (CK) leakage from the rat isolated perfused haert. The inactive isomer L-naloxone decreased the CK release by half. The (-antagonist ICI 174,864 and k-antagonist nor-binanltorphimine exerted a weaker protective effect. The (-antagonist DAMGO, the (2-agonist DSLET, the k1-agonist spiradolin, or the sigma-agonist (+)-SKF 10047, improved myocardial cell viability after ischemia/reperfusion.
 ...
PMID:[Opioid system and cardiac resistance to ischemic and reperfusion injuries]. 1080 7

We investigated the effects of phytoestrogen on global myocardial ischemia-reperfusion injury in five groups of female rats. A high-phytoestrogen group (HPE) was ovariectomized (Ovx) and fed a diet containing soybean protein and a high-isoflavone soy extract. Another Ovx group of rats was fed the same diet as the HPE group but treated with the estrogen receptor blocker ICI-182,780 (HPE + ICI). A third group of Ovx rats was fed a diet containing soybean protein alone (low-phytoestrogen content; LPE). A fourth Ovx group was fed a diet free of phytoestrogen (Ovx). The fifth group of rats was sham ovariectomized (sham). Hearts from all rats were subjected to 30 min of global, hypothermic (4 degrees C), cardioplegic ischemia and 120 min of normothermic (37 degrees C) reperfusion with oxygenated Krebs-Henseleit buffer. Compared with either the sham or the HPE group, the Ovx and HPE + ICI groups had significantly decreased first derivative of left ventricular pressure (dP/dt), coronary flow rate (CFR), nitrite production and mitochondrial respiratory function and significantly increased Ca2+ accumulation and myocardial histological and ultrastructural injury. The CFR of the LPE group was significantly different from that of either Ovx or HPE + ICI group but the dP/dt, nitrite production, Ca2+ accumulation, and mitochondrial function were not. Our results indicate that diets containing phytoestrogen extract play a cardioprotective role in global myocardial ischemia-reperfusion in female rats.
 ...
PMID:Effects of dietary phytoestrogen on global myocardial ischemia-reperfusion injury in isolated female rat hearts. 1151 91

We have previously demonstrated that estradiol reduces cell death in cortical explant cultures following injury induced by metabolic inhibition in a receptor-dependent fashion. In this study, we examined whether cell death involves apoptosis and assessed the potential mediators of estradiol's actions. Cortical explant cultures were generated from postnatal day 3 rat pups. On day 7 in vitro, explants were injured by exposure to 1 mM 2-DG/2 mM KCN for 2 h to model the metabolic inhibition observed during ischemia. Explants were fixed in 4% paraformaldehyde at 2, 6, 10 and 24 h following the injury period and 18-microm thick sections were cut on a cryostat and stained with cresyl violet to assess cell death. The same sections were also labeled by TUNEL to determine whether cell death occurred by apoptosis. Other sections were used for immunohistochemistry to determine whether cells that stained positive for activated caspase 3 were also immunopositive for NeuN, a neuronal marker, or GFAP, an astrocyte marker. Protein was extracted for Western blot analysis from a separate set of explants collected at 0, 0.5, 1, 2 and 4 h following the conclusion of the injury. Estradiol treatment significantly reduced the number of cells undergoing apoptotic cell death as indicated by nuclear condensation visualized by cresyl violet staining (P<0.05). TUNEL staining revealed that the majority of pyknotic and fragmented nuclei were also TUNEL positive. Furthermore, caspase 3 activation appeared to be restricted to neurons. To examine a possible mechanism by which estradiol prevents apoptosis, we examined the level of activation of Akt kinase, which mediates antiapoptotic signals. Potential activation was measured by phosphorylation of Akt at Ser473 by Western blot analysis. In the absence of estradiol, pAkt levels were significantly increased at 2 h following the termination of injury. Explants that were pretreated with estradiol exhibited elevated levels of pAkt at 1 h following injury. Treatment with ICI 182,780 prevented the effect of estradiol. These studies suggest that estradiol prevents injury-induced apoptosis and that Akt activation may mediate these protective effects.
 ...
PMID:Estradiol enhances Akt activation in cortical explant cultures following neuronal injury. 1219 93

Using an isolated nonworking rat heart model, this study investigated the role of beta-adrenergic preconditioning (beta-PC) to attenuate myocardial dysfunction after an ischemia/reperfusion injury. After a 20-min stabilization period, the noradrenaline depleted hearts were perfused for 5 min with isoproterenol (ISO) before 40-min global ischemia (I) followed by 30-min reperfusion (R). ISO 0.02 microM provided significant protection versus unconditioned in vivo reserpinized IR control, causing a decrease of creatine kinase (CK) release (mIU/min/g wet weight) on reperfusion in coronary effluent, a preservation of the mean coronary flow (MCF) and preservation of left ventricular function assessed by the rate-pressure product (RPP). These beneficial effects were similar to those of ischemic preconditioning (I-PC) in both nonreserpinized and reserpinized rats. Propranolol (1 microM) and atenolol (10 microM) completely suppressed the ISO preconditioning. In contrast, ICI 118551 (2 microM) a highly selective beta -blocker, did not blunt the salutary effects of ISO on CK release and MCF preservation. These results indicate that ISO pretreatment provides a significant cardioprotection against prolonged ischemic myocardial injury. Although endogenous catecholamines are not necessary for I-PC in isolated rat hearts, cardioprotection provided by beta-adrenergic stimulation is quite similar to I-PC. This significant cardioprotection is mediated less by beta -adrenoceptor than by beta -adrenoceptor activation, which seems to play a crucial role in the beta-PC mechanism.
 ...
PMID:Role of beta 1- and beta 2-adrenoceptor subtypes in preconditioning against myocardial dysfunction after ischemia and reperfusion. 1260 18

We have developed a model for prenatal hypoxia-ischemia in which muscimol, a selective gamma-aminobutyric acid A (GABA(A)) receptor agonist, administered to newborn rats, induces hippocampal damage. In the neonatal rat brain, activation of GABA(A) receptors leads to membrane depolarization and neuronal excitation. Because of our previous detection of sex differences in this model and the considerable interest in the neuroprotective effects of estradiol in the adult brain, we now investigate the effect of pretreatment with high physiological levels of estradiol in our model of prenatal hypoxia-ischemia. We used unbiased stereology to assess neuron number in the hippocampal formation of control, muscimol-treated, and estradiol- plus muscimol-treated animals. Muscimol decreased neuron number in the hippocampus, with damage exacerbated by pretreatment with estradiol. A hippocampal culture paradigm was developed to mirror the in vivo investigation. We observed elevated cytotoxicity (using the lactate dehydrogenase assay) by 48 h after treatment with estradiol plus muscimol, but decreased cytotoxicity between 2 and 24 h after treatment. To determine whether the actions of estradiol on muscimol-induced damage were via the estrogen receptor, hippocampal cultures were pretreated with ICI 182,780, a selective estrogen receptor antagonist. Treatment with ICI 182,780 blocked the potentiating effect of estradiol on the late period of cytotoxicity, but had no effect on the protective actions of estradiol during the early period of cytotoxicity. There appears to be a biphasic action of estradiol in our model of neonatal brain injury that involves early nongenomic, nonreceptor-mediated protection, followed by late deleterious receptor-mediated effects.
 ...
PMID:Estradiol exacerbates hippocampal damage in a model of preterm infant brain injury. 1274 95


1 2 3 4 5 Next >>