Document Detail


Role of NADPH Oxidase and Xanthine Oxidase in Mediating Inducible VT/VF and Triggered Activity in a Canine Model of Myocardial Ischemia.
MedLine Citation:
PMID:  25375191     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block VT/VF.
METHODS: 69 dogs received apocynin (APO), 4 mg/kg intraveneously (IV), oxypurinol (OXY), 4 mg/kg IV, or both APO and OXY (BOTH) agents, or saline 3 h after coronary occlusion. Endocardium from ischemic sites (3-D mapping) was sampled for Rac1 (GTP-binding protein in membrane NADPH oxidase) activation or standard microelectrode techniques. Results (mean ± SE, * p < 0.05): VT/VF originating from ischemic zones was blocked by APO in 6/10 *, OXY in 4/9 *, BOTH in 5/8 * or saline in 1/27; 11/16 VT/VFs blocked were focal. In isolated myocardium, TA was blocked by APO (10-6 M) or OXY (10-8 M). Rac1 levels in ischemic endocardium were decreased by APO or OXY.
CONCLUSION: APO and OXY suppressed focal VT/VF due to DADs, but the combination of the drugs was not more effective than either alone. Both drugs inhibited ischemic Rac1 with inhibition by OXY suggesting ROS-induced ROS. The inability to totally prevent VT/VF suggests that other mechanisms also contribute to ischemic VT.
Authors:
James B Martins; Ashok K Chaudhary; Shuxia Jiang; Michael Kwofie; Prescott Mackie; Francis J Miller
Publication Detail:
Type:  Journal Article     Date:  2014-11-04
Journal Detail:
Title:  International journal of molecular sciences     Volume:  15     ISSN:  1422-0067     ISO Abbreviation:  Int J Mol Sci     Publication Date:  2014  
Date Detail:
Created Date:  2014-11-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101092791     Medline TA:  Int J Mol Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  20079-100     Citation Subset:  IM    
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