| Production of endothelin-1 and reduced blood flow in the rat kidney during lung-injurious mechanical ventilation. | |
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MedLine Citation:
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PMID: 18806040 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: The mechanisms by which mechanical ventilation (MV) can injure remote organs, such as the kidney, remain poorly understood. We hypothesized that upregulation of systemic inflammation, as reflected by plasma interleukin-6 (IL-6) levels, in response to a lung-injurious ventilatory strategy, ultimately results in kidney dysfunction mediated by local endothelin-1 (ET-1) production and renal vasoconstriction. METHODS: Healthy, male Wistar rats were randomized to 1 of 2 MV settings (n=9 per group) and ventilated for 4 h. One group had a lung-protective setting using peak inspiratory pressure of 14 cm H2O and a positive end-expiratory pressure of 5 cm H2O; the other had a lung-injurious strategy using a peak inspiratory pressure of 20 cm H2O and positive end-expiratory pressure of 2 cm H2O. Nine randomly assigned rats served as nonventilated controls. We measured venous and arterial blood pressure and cardiac output (thermodilution method), renal blood flow (RBF) using fluorescent microspheres, and calculated creatinine clearance, urine flow, and fractional sodium excretion. Histological lung damage was assessed using hematoxylin-eosin staining. Renal ET-1 and plasma ET-1 and IL-6 concentrations were measured using enzyme-linked immunosorbent assays. RESULTS: Lung injury scores were higher after lung-injurious MV than after lung-protective ventilation or in sham controls. Lung-injurious MV resulted in significant production of renal ET-1 compared with the lung-protective and control groups. Simultaneously, RBF in the lung-injurious MV group was approximately 40% lower (P<0.05) than in the control group and 28% lower (P<0.05) than in the lung-protective group. Plasma ET-1 and IL-6 levels did not differ among the groups and systemic hemodynamics, such as cardiac output, were comparable. There was no effect on creatinine clearance, fractional sodium excretion, urine output, or kidney histology. CONCLUSIONS: Lung-injurious MV for 4 h in healthy rats results in significant production of renal ET-1 and in decreased RBF, independent of IL-6. Decreased RBF has no observable effect on kidney function or histology. |
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Authors:
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Jan Willem Kuiper; Amanda M G Versteilen; Hans W M Niessen; Rosanna R Vaschetto; Pieter Sipkema; Cobi J Heijnen; A B Johan Groeneveld; Frans B Plötz |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesia and analgesia Volume: 107 ISSN: 1526-7598 ISO Abbreviation: Anesth. Analg. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-09-22 Completed Date: 2008-10-09 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: United States |
Other Details:
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Languages: eng Pagination: 1276-83 Citation Subset: AIM; IM |
Affiliation:
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VU Medical Center, Department of Pediatric Intensive Care, P.O. Box 7057, 1007, Ambsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Creatinine / metabolism Diuresis Endothelin-1 / biosynthesis* Interleukin-6 / blood Kidney / metabolism* Kidney Diseases / etiology Lung / pathology Lung Injury* Male Rats Rats, Wistar Renal Circulation* Respiration, Artificial / adverse effects* Sodium / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1; 0/Interleukin-6; 60-27-5/Creatinine; 7440-23-5/Sodium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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