Document Detail


Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution.
MedLine Citation:
PMID:  22972685     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery.
BACKGROUND: Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium.
METHODS: In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery.
RESULTS: IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route.
CONCLUSIONS: Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.
Authors:
Soon Jun Hong; Dongming Hou; Todd J Brinton; Brian Johnstone; Dongni Feng; Pamela Rogers; William F Fearon; Paul Yock; Keith L March
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-10-07
Journal Detail:
Title:  Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions     Volume:  83     ISSN:  1522-726X     ISO Abbreviation:  Catheter Cardiovasc Interv     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2013-12-18     Completed Date:  2014-08-18     Revised Date:  2014-10-03    
Medline Journal Info:
Nlm Unique ID:  100884139     Medline TA:  Catheter Cardiovasc Interv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E17-25     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / cytology*
Animals
Cell Tracking / methods
Coronary Circulation*
Coronary Vessels / physiopathology*
Disease Models, Animal
Infusions, Intra-Arterial
Infusions, Intravenous
Lung / blood supply*,  radionuclide imaging
Microcirculation
Myocardial Infarction / pathology,  physiopathology,  radionuclide imaging,  surgery*
Myocardium / pathology*
Pulmonary Circulation*
Stem Cell Transplantation / adverse effects,  methods*
Swine
Time Factors
Tomography, Emission-Computed, Single-Photon
Vascular Resistance
Grant Support
ID/Acronym/Agency:
R01 HL077688/HL/NHLBI NIH HHS; R01 HL077688/HL/NHLBI NIH HHS; R01 HL105772/HL/NHLBI NIH HHS

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