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)

Operative mortality in lung transplantation in many centers has decreased to less than 10%. Despite this improvement in early survival, delayed graft failure related to chronic graft rejection continues to limit the survival and function of lung transplant recipients. Chronic lung transplant rejection Bronchiolitis obliterans (BO) is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The histological changes are manifest by a progressive obstructive ventilatory defect on spirometric testing. Histologic diagnosis of BO is difficult due to sampling. The term BO syndrome has been developed to allow clinical diagnosis using spirometric criteria. BO is an alloimmune phenomenon, aggravated by airway ischemia, and infection but predicted by frequent and severe acute vascular rejection. It is characterized by increased expression of TGF beta and other cytokines on airway epithelial cells, increased expression of class II antigens in the airways, lymphocytic bronchiolitis, and bronchial epithelial cell proliferation mediated by numerous cytokines. Airway neutrophilia, and activation of neutrophilis with release of their granules into the airway is a precursor of progressive BO. Loss of normal protective mechanisms--leukocyte antiproteases--against this oxidative insult may be an integral part of disease progression. To date treatment of BOS is infrequently successful. Better understanding of the pathophysiology, and earlier recognition of BO may result in improved long term patient and graft survival and function.
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PMID:Bronchiolitis obliterans: the Achilles heel of lung transplantation. 1264 79

The purpose of this study was to investigate the effects of bosentan, a mixed endothelin receptor A and B subtype antagonist, on myocardial ischemia-reperfusion injury and to explore the influence of the timing of bosentan administration on its cardioprotective effects. Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow rate at 10 mL/min. Global myocardial ischemia was induced by stopping KH perfusion for 40 min, and this was followed by 60 min of reperfusion. Hearts were randomized to 1 of 3 experimental groups (n = 7 each): untreated control; treatment with bosentan 1 micromol/L 10 min prior to, during 40 min global ischemia, and for 15 min of reperfusion (BOS); or treatment with bosentan 1 micromol/L after 15 min of reperfusion (BOS-R). We observed that BOS-R, but not the BOS treatment regimen, significantly reduced the release of cardiac-specific creatine kinase and postischemic myocardial infarct size (P < 0.05 vs. control) without affecting myocardial contractility. Left ventricular developed pressure in the BOS group was significantly (P < 0.01) lower than that in the control group throughout reperfusion. It is concluded that pharmacologically delayed antagonism of endothelin-1 during reperfusion attenuates postischemic myocardial injury. Endothelin-1 antagonist application during early reperfusion may exacerbate postischemic myocardial dysfunction.
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PMID:Endothelin A and B receptor antagonist bosentan reduces postischemic myocardial injury in the rat: critical timing of administration. 1587 Aug 40

Endothelin-1 has been shown to be associated with greater myocardial ischemia and reperfusion injury in which oxidative stress plays a key role. The efficacy of bosentan, a mixed ETA-ETB endothelin receptor antagonist, in protecting the myocardium from ischemia-reperfusion injury and oxidative stress was studied in open-chest Wistar rats. Anesthetized adult male rats (175-250 g b wt) underwent sham operation (SHAM group) or were subjected to 40 min of myocardial ischemia (MI) induced by temporary occlusion of the left anterior descending coronary artery (LAD) followed by 2 h reperfusion (R). Rats submitted to the MI-R protocol were administered bosentan at a dose of 3 mg/kg i.v. 20 min (BOS group) or saline (CON group) 20 min post-occlusion of LAD. After the 2 h reperfusion period the animals were euthanized and the heart rapidly excised. Cardiac tissue samples were snap frozen in liquid nitrogen for biochemical assay and were fixed in 10% formalin solution for histologic evaluation. Myocardial I-R resulted in a significant increase (p < 0.05) in the myocardial malondialdehyde levels and a decrease (p < 0.01) in the myocardial reduced glutathione content. These changes were associated with significant decreases in the myocardial activity of antioxidant enzymes superoxide dismutase (p < 0.05) and catalase (p < 0.01) and severe tissue damage in the jeopardized myocardium in the CON group as compared with the non-myocardial ischemia-reperfusion (NMI-R) SHAM group. Bosentan exerted marked tissue protective effect as assessed by histologic evaluation of the myocardium. The drug significantly (p < 0.05) attenuated myocardial oxidative stress and restored the cellular antioxidant defense mechanisms as compared with the saline-treated controls subjected to the MI-R protocol. Furthermore, bosentan also exerted a marked effect on peripheral hemodynamics and heart rate during the reperfusion phase (data reported elsewhere). These results are consistent with the concept that endothelin-1 may be involved in the pathogenesis of myocardial ischemia and infarction. This study demonstrates the antioxidant effect of non-selective endothelin receptor antagonism elucidating that, part of the aetiology of ischemia and reperfusion induced myocardial injury involves impaired antioxidant defenses.
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PMID:Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. 1633 85