Document Detail


Effects of myocardial infarction on the distribution and transport of nutrients and oxygen in porcine myocardium.
MedLine Citation:
PMID:  23083196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of the primary limitations of cell therapy for myocardial infarction is the low survival of transplanted cells, with a loss of up to 80% of cells within 3 days of delivery. The aims of this study were to investigate the distribution of nutrients and oxygen in infarcted myocardium and to quantify how macromolecular transport properties might affect cell survival. Transmural myocardial infarction was created by controlled cryoablation in pigs. At 30 days post-infarction, oxygen and metabolite levels were measured in the peripheral skeletal muscle, normal myocardium, the infarct border zone, and the infarct interior. The diffusion coefficients of fluorescein or FITC-labeled dextran (0.3-70 kD) were measured in these tissues using fluorescence recovery after photobleaching. The vascular density was measured via endogenous alkaline phosphatase staining. To examine the influence of these infarct conditions on cells therapeutically used in vivo, skeletal myoblast survival and differentiation were studied in vitro under the oxygen and glucose concentrations measured in the infarct tissue. Glucose and oxygen concentrations, along with vascular density were significantly reduced in infarct when compared to the uninjured myocardium and infarct border zone, although the degree of decrease differed. The diffusivity of molecules smaller than 40 kD was significantly higher in infarct center and border zone as compared to uninjured heart. Skeletal myoblast differentiation and survival were decreased stepwise from control to hypoxia, starvation, and ischemia conditions. Although oxygen, glucose, and vascular density were significantly reduced in infarcted myocardium, the rate of macromolecular diffusion was significantly increased, suggesting that diffusive transport may not be inhibited in infarct tissue, and thus the supply of nutrients to transplanted cells may be possible. in vitro studies mimicking infarct conditions suggest that increasing nutrients available to transplanted cells may significantly increase their ability to survive in infarct.
Authors:
Bryce H Davis; Yoshihisa Morimoto; Chris Sample; Kevin Olbrich; Holly A Leddy; Farshid Guilak; Doris A Taylor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of biomechanical engineering     Volume:  134     ISSN:  1528-8951     ISO Abbreviation:  J Biomech Eng     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-04-25     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  7909584     Medline TA:  J Biomech Eng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  101005     Citation Subset:  IM    
Affiliation:
Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Cell Death
Cell Differentiation
Cell Hypoxia
Cell Line
Cell Proliferation
Diffusion
Glucose / metabolism
Mice
Myoblasts, Skeletal / pathology
Myocardial Infarction / metabolism*,  pathology*
Myocardium / metabolism*,  pathology
Oxygen / metabolism*
Swine
Grant Support
ID/Acronym/Agency:
AG15768/AG/NIA NIH HHS; AR48182/AR/NIAMS NIH HHS; AR48852/AR/NIAMS NIH HHS; AR50245/AR/NIAMS NIH HHS; HL63346/HL/NHLBI NIH HHS; HL63703/HL/NHLBI NIH HHS; P01 AR050245/AR/NIAMS NIH HHS; R01 AG015768/AG/NIA NIH HHS; R01 AR048182/AR/NIAMS NIH HHS; R01 AR048852/AR/NIAMS NIH HHS; R01 HL063346/HL/NHLBI NIH HHS; R01 HL063703/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
50-99-7/Glucose; 7782-44-7/Oxygen
Comments/Corrections

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