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Abstract

Due to the increasing need for kidney donors, transplantation from non-heart-beating donors (NHBD) is currently being practiced more extensively. As detailed studies on the reperfusion injury of these kidneys do not exist so far, a comparison of renal ischemia reperfusion injury scores immediately after organ explantation with injury scores after NHBD organ explantation with subsequent cold storage would be useful. Non-stored kidneys were compared to a group of kidneys stored for 6.9 +/- 1.8 h. Functional analyses were made during 145 min of ex vivo perfusion. Quantitative histological analyses were performed in all kidneys after termination of perfusion. During ex vivo reperfusion, renal vascular resistance was elevated, while creatinine clearance, filtration fraction, renal oxygen consumption, and sodium reabsorption were below normal after non-heart-beating explantation and further decreased after subsequent washing and cold storage. In the kidneys subjected to cold preservation, histologically tubular damage was enhanced, and the total count, as well that for the intraglomerular neutrophil granulocytes were also elevated. Explantation from NHBD causes renal ischemia reperfusion injury. Cold storage augmented deterioration of the kidney as histologically and functionally demonstrated. Thus, preservation times for non-heart-beating kidneys should be carefully reappraised. Copyright 2004 S. Karger AG, Basel

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Expression of respiratory mucins in fatal status asthmaticus and mild asthma.

Louis B. Harrison, K. Fan Chung, Garth A Nicholson … (2002)

The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T-cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gel-forming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated. Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n=5) and from mild asthmatics (n=4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs, adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment. The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.

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Histological evaluation of proximal tubule cell injury in isolated perfused pig kidneys exposed to cold ischemia.

P Levillain, M Carretier, Thierry Hauet … (1999)

Ischemic injury of the renal allograft before transplantation is a major cause of impaired graft function. Proton nuclear spectroscopy provides a useful technique for evaluating proximal tubular activity. In addition to this technique, we proposed a histological grading system for quantifying proximal tubule alterations. The aim of this study was to evaluate the histological lesions of tubule epithelial cells in the model of isolated perfused pig kidneys following 48 to 72 h of cold storage in Euro-Collins solution. Normothermic isolated perfused pig kidneys were randomized in three experimental groups : Group 1, control group; cold flush with cold heparinized solution followed by immediate reperfusion (n = 6); Group 2, 48 h of cold storage in Euro-Collins followed by reperfusion (n = 6); Group 3, 72 h of cold storage in Euro-Collins followed by reperfusion (n = 6). Proton nuclear spectroscopy of urine and biochemical studies were performed for whole renal functional evaluation during reperfusion. Optical and electron microscopy analyses of the reperfused kidneys were performed by four investigators and the degree of cell injury was assessed using 8 different criteria in a 5-scale numerical score. Numerical scores corroborate the results from NMR spectroscopy and differed significantly between the three groups studied. The degree of proximal tubule cell damage was increased with prolonged cold ischemia as shown particularly in Group 3. The results from this study showed that analysis of cell injury based on an histological grading system in the model of isolated perfused kidney allows the quantification of the degree of proximal tubule injury. Thus, such morphological system analysis could be a useful method for quantifying tubule cell injuries observed under various physiopathological conditions. Copyright 1999 Academic Press.

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Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.

William Cooper, Ignacio Duarte, Vinod H Thourani … (2000)

Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside. In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%). In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%). Apoptosis (DNA laddering) occurred primarily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%). DHCA is associated with endothelial dysfunction in cerebral microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.

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PubMed ID:: 15056986

DOI:: 10.1159/000076751

ScienceOpen disciplines: Chemistry

Keywords: Animals,Cold Temperature,Kidney,blood supply,pathology,physiopathology,Kidney Transplantation,Organ Culture Techniques,Organ Preservation,Reperfusion Injury,etiology,Swine,Tissue Donors

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Influence of cold storage on renal ischemia reperfusion injury after non-heart-beating donor explantation.

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Abstract

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Karger: Nephrology

Most cited references 16

Expression of respiratory mucins in fatal status asthmaticus and mild asthma.

Histological evaluation of proximal tubule cell injury in isolated perfused pig kidneys exposed to cold ischemia.

Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.

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