Document Detail


Transmural distribution of metabolic abnormalities and glycolytic activity during dobutamine-induced demand ischemia.
MedLine Citation:
PMID:  18424629     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The heterogeneity across the left ventricular wall is characterized by higher rates of oxygen consumption, systolic thickening fraction, myocardial perfusion, and lower energetic state in the subendocardial layers (ENDO). During dobutamine stimulation-induced demand ischemia, the transmural distribution of energy demand and metabolic markers of ischemia are not known. In this study, hemodynamics, transmural high-energy phosphate (HEP), 2-deoxyglucose-6-phosphate (2-DGP) levels, and myocardial blood flow (MBF) were determined under basal conditions, during dobutamine infusion (DOB: 20 microg x kg(-1) x min(-1) iv), and during coronary stenosis + DOB + 2-deoxyglucose (2-DG) infusion. DOB increased rate pressure products (RPP) and MBF significantly without affecting the subendocardial-to-subepicardial blood flow ratio (ENDO/EPI) or HEP levels. During coronary stenosis + DOB + 2-DG infusion, RPP, ischemic zone (IZ) MBF, and ENDO/EPI decreased significantly. The IZ ratio of creatine phosphate-to-ATP decreased significantly [2.30 +/- 0.14, 2.06 +/- 0.13, and 2.04 +/- 0.11 to 1.77 +/- 0.12, 1.70 +/- 0.11, and 1.72 +/- 0.12 for EPI, midmyocardial (MID), and ENDO, respectively], and 2-DGP accumulated in all layers, as evidenced by the 2-DGP/PCr (0.55 +/- 0.12, 0.52 +/- 0.10, and 0.37 +/- 0.08 for EPI, MID, and ENDO, respectively; P < 0.05, EPI > ENDO). In the IZ the wet weight-to-dry weight ratio was significantly increased compared with the normal zone (5.9 +/- 0.5 vs. 4.4 +/- 0.4; P < 0.05). Thus, in the stenotic perfused bed, during dobutamine-induced high cardiac work state, despite higher blood flow, the subepicardial layers showed the greater metabolic changes characterized by a shift toward higher carbohydrate metabolism, suggesting that a homeostatic response to high-cardiac work state is characterized by more glucose utilization in energy metabolism.
Authors:
Mohammad N Jameel; Xiaohong Wang; Marcel H J Eijgelshoven; Abdul Mansoor; Jianyi Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-04-18
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  294     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-09     Completed Date:  2008-08-15     Revised Date:  2011-03-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2680-6     Citation Subset:  IM    
Affiliation:
Cardiovascular Division, Departments of Medicine, University of Minnesota Medical School. Minneapolis, Minnesota, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Coronary Circulation
Coronary Stenosis / complications*,  metabolism,  physiopathology
Disease Models, Animal
Dobutamine
Dogs
Endocardium / metabolism
Energy Metabolism*
Glucose-6-Phosphate / analogs & derivatives,  metabolism
Glycolysis*
Hemodynamics
Lactic Acid / metabolism
Magnetic Resonance Spectroscopy
Myocardial Ischemia / chemically induced,  etiology,  metabolism*,  physiopathology
Myocardium / metabolism*,  pathology
Oxygen Consumption
Pericardium / metabolism
Phosphocreatine / metabolism
Grant Support
ID/Acronym/Agency:
HL-50470/HL/NHLBI NIH HHS; HL-61353/HL/NHLBI NIH HHS; HL-67828/HL/NHLBI NIH HHS; R01 HL050470-12/HL/NHLBI NIH HHS; R01 HL061353-05/HL/NHLBI NIH HHS; R01 HL067828-06/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
34368-04-2/Dobutamine; 3573-50-0/2-deoxyglucose-6-phosphate; 50-21-5/Lactic Acid; 56-65-5/Adenosine Triphosphate; 56-73-5/Glucose-6-Phosphate; 67-07-2/Phosphocreatine
Comments/Corrections

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