| Protective effects of nitric oxide synthase 3 and soluble guanylate cyclase on the outcome of cardiac arrest and cardiopulmonary resuscitation in mice. | |
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MedLine Citation:
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PMID: 19050616 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Despite advances in resuscitation methods, survival after out-of-hospital cardiac arrest remains low, at least in part, due to postcardiac arrest circulatory and neurologic failure. To elucidate the role of nitric oxide (NO) in the recovery from cardiac arrest and cardiopulmonary resuscitation (CPR), we studied the impact of NO synthase (NOS3)/cGMP signaling on cardiac and neurologic outcomes after cardiac arrest and CPR. DESIGN: Prospective, randomized, controlled study. SETTING: Animal research laboratory. SUBJECTS: Mice. INTERVENTIONS: Female wild-type (WT) mice, NOS3-deficient mice (NOS3-/-), NOS3-/- mice with cardiomyocyte-specific overexpression of NOS3 (NOS3-/-CSTg), and mice deficient for soluble guanylate cyclase alpha1 (sGCalpha1-/-) were subjected to potassium-induced cardiac arrest (9 min) followed by CPR. Cardiac and neurologic function and survival were assessed up to 24 hrs post-CPR. MEASUREMENTS AND MAIN RESULTS: Cardiac arrest and CPR markedly depressed myocardial function in NOS3-/- and sGCalpha1-/- but not in WT and NOS3-/-CSTg. Neurologic function score and 24 hrs survival rate was lower in NOS3-/- and sGCalpha1-/- compared with WT and NOS3-/-CSTg. Detrimental effects of deficiency of NOS3 or sGCalpha1 were associated with enhanced inflammation of heart and liver and increased cell death in heart, liver, and brain that were largely prevented by cardiomyocyte-restricted NOS3 overexpression. CONCLUSIONS: These results demonstrate an important salutary impact of NOS3/sGC signaling on the outcome of cardiac arrest. Myocardial NOS3 prevented postcardiac arrest myocardial dysfunction, attenuated end-organ damage, and improved neurologic outcome and survival. Our observations suggest that enhancement of cardiac NOS3 and/or sGC activity may improve outcome after cardiac arrest and CPR. |
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Authors:
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Takefumi Nishida; Jia De Yu; Shizuka Minamishima; Patrick Y Sips; Robert J Searles; Emmanuel S Buys; Stefan Janssens; Peter Brouckaert; Kenneth D Bloch; Fumito Ichinose |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Critical care medicine Volume: 37 ISSN: 1530-0293 ISO Abbreviation: Crit. Care Med. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-02 Completed Date: 2009-02-09 Revised Date: 2011-05-06 |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 256-62 Citation Subset: AIM; IM |
Affiliation:
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Anesthesia Center for Critical Care Research, Department of Anesthesia and Critical Car), Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiopulmonary Resuscitation* Female Guanylate Cyclase / physiology* Heart Arrest / therapy* Mice Nitric Oxide Synthase Type III / physiology* Receptors, Cytoplasmic and Nuclear / physiology* Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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GM79360/GM/NIGMS NIH HHS; HL70896/HL/NHLBI NIH HHS; HL71987/HL/NHLBI NIH HHS; K08 HL071987-05/HL/NHLBI NIH HHS; R01 GM079360-01/GM/NIGMS NIH HHS; R01 HL070896-01A1/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Cytoplasmic and Nuclear; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/soluble guanylyl cyclase |
| Comments/Corrections | |
Comment In:
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Crit Care Med. 2009 Jan;37(1):368-9
[PMID:
19112311
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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