| Genetic deletion of NOS3 increases lethal cardiac dysfunction following mouse cardiac arrest. | |
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MedLine Citation:
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PMID: 20951489 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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STUDY AIMS: Cardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3(-/-)) mice. METHODS: Adult female wild-type (WT) and NOS3(-/-) mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured. RESULTS: Despite equal quality CPR, NOS3(-/-) mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], p<0.005). Among ROSC animals, NOS3(-/-) vs. WT mice exhibited increased left-ventricular dysfunction and 120min mortality. Prior to ROSC, myocardial effectors of NO signaling including cGMP and p-TnI were decreased in NOS3(-/-) vs. WT mice (p<0.05). Following ROSC in WT mice, significant NOS3-dependent increases in circulating HbNO were seen by 120min. Significant increases in cardiac p-NOS3 occurred between end-arrest and 15min post-ROSC, while total NOS3 content was increased by 120min post-ROSC (p<0.05). CONCLUSIONS: Genetic deletion of NOS3 decreases ROSC rate and worsens post-ROSC left-ventricular function. Poor cardiovascular outcomes are associated with differences in NOS3-dependent myocardial cGMP signaling and circulating NO metabolites. |
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Authors:
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David G Beiser; Gerasim A Orbelyan; Brendan T Inouye; James G Costakis; Kimm J Hamann; Elizabeth M McNally; Terry L Vanden Hoek |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-16 |
Journal Detail:
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Title: Resuscitation Volume: 82 ISSN: 1873-1570 ISO Abbreviation: Resuscitation Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-10 Completed Date: 2011-05-17 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 0332173 Medline TA: Resuscitation Country: Ireland |
Other Details:
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Languages: eng Pagination: 115-21 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Emergency Resuscitation Center, Section of Emergency Medicine, University of Chicago, 5841 S. Maryland Ave., MC 5068, Chicago, IL 60637, USA. dbeiser@uchicago.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cardiopulmonary Resuscitation / methods DNA / genetics* Disease Models, Animal Female Gene Deletion* Heart Arrest / enzymology, genetics*, therapy Mice Mice, Inbred C57BL Myocardium / enzymology Nitric Oxide Synthase Type III / genetics* Ventricular Dysfunction, Left / enzymology, etiology, genetics* |
| Grant Support | |
ID/Acronym/Agency:
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5K08HL091184/HL/NHLBI NIH HHS; HL079641/HL/NHLBI NIH HHS; HL084643/HL/NHLBI NIH HHS; HL61322/HL/NHLBI NIH HHS; HL68951/HL/NHLBI NIH HHS; HL78926/HL/NHLBI NIH HHS; K08 HL091184-02/HL/NHLBI NIH HHS; K08 HL091184-03/HL/NHLBI NIH HHS; K08 HL091184-04/HL/NHLBI NIH HHS; R01 HL061322-12/HL/NHLBI NIH HHS; R01 HL068951-05/HL/NHLBI NIH HHS; R01 HL078926-05W1/HL/NHLBI NIH HHS; R01 HL079641-05/HL/NHLBI NIH HHS; R01 HL084643-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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9007-49-2/DNA; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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