Document Detail


Acute and chronic effects of transient myocardial ischemia on sympathetic nerve activity, density, and norepinephrine content.
MedLine Citation:
PMID:  7585815     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The sympathetic nervous system has profound influences on myocardial function, particularly during ischemia. There is controversy, however, as to whether myocardial ischemia results in damage to myocardial sympathetic nerves coursing through the ischemic territory. To further evaluate these issues, we assessed the acute and chronic effects of transient myocardial ischemia on sympathetic nerve function and morphology. METHODS: A total of 20 dogs were studied. For acute studies (n = 9), we performed serial dynamic imaging of I-123 metaiodobenzylguanidine (MIBG) washout during coronary occlusion and reperfusion, and assessed residual myocardial perfusion with thallium-201. For chronic studies (n = 11), we assessed sympathetic innervation and perfusion 11 days following a transient intracoronary balloon occlusion. Imaging results were correlated with electrocardiographic responses, histology, and tissue norepinephrine (NE). RESULTS: In the acute studies, regional MIBG washout increased more than 2-fold in the ischemic territory compared to the control region during coronary occlusion (14.2 +/- 2.3 vs. 5.9 +/- 1.2%, P < 0.01). Tissue NE was reduced in the ischemic territory compared to the non-ischemic territory (335 +/- 162 vs. 751 +/- 190 ng/g, P < 0.01). Myocardial perfusion was normal. In the chronic studies, 9/11 dogs showed ischemic ECG changes during balloon occlusion, and developed ventricular arrhythmias. On follow-up imaging, 5/11 dogs showed reduced MIBG uptake relative to thallium, in viable myocardium overlying necrotic subendocardium, reduced NE (226 +/- 77 vs. 733 +/- 82 ng/g in control regions, P < 0.01), decreased nerve density, and a larger extent of denervation than scar (25.5 +/- 3.7 vs. 8.2 +/- 2.7%, P < 0.02). Six of 11 dogs showed normal innervation patterns. CONCLUSIONS: These studies suggest that the sympathetic nerves are acutely affected in regions of myocardial ischemia as detected by enhanced regional washout of MIBG. In addition, chronic sympathetic nerve denervation can occur in the absence of transmural myocardial necrosis; however, the occurrence of transient ischemia does not predict the development of chronic denervation. The severity of ischemia, as evidenced by the extent of the related necrosis, does appear to predict chronic denervation. The severity of ischemia, as evidenced by the extent of the related necrosis, does appear to predict chronic denervation. The mechanisms leading to chronic denervation of sympathetic nerves in the absence of transmural infarction remain to be defined.
Authors:
M W Dae; J W O'Connell; E H Botvinick; M C Chin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cardiovascular research     Volume:  30     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-12-12     Completed Date:  1995-12-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  270-80     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Institute, University of California, San Francisco 94143, USA.
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MeSH Terms
Descriptor/Qualifier:
3-Iodobenzylguanidine
Acute Disease
Animals
Chronic Disease
Dogs
Electrocardiography
Heart / radionuclide imaging
Image Processing, Computer-Assisted
Iodine Radioisotopes
Iodobenzenes
Microscopy, Fluorescence
Myocardial Ischemia / metabolism,  physiopathology*,  radionuclide imaging
Myocardial Reperfusion
Myocardium / metabolism
Norepinephrine / metabolism*
Sympathetic Nervous System / physiopathology*
Sympathomimetics / metabolism*
Grant Support
ID/Acronym/Agency:
HL25847/HL/NHLBI NIH HHS; HL38105/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Iodine Radioisotopes; 0/Iodobenzenes; 0/Sympathomimetics; 51-41-2/Norepinephrine; 77679-27-7/3-Iodobenzylguanidine

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