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Title: Hypercholesterolemia in minipigs impairs left ventricular response to stress: association with decreased coronary flow reserve and reduced capillary density
Authors: Theilmeier, Gregor ×
Verhamme, Peter
Beck, Heike
Bernar, Hilde
Lox, Marleen
Janssens, Stefan
Herregods, Marie-Christine
Verbeken, Eric
Plate, Karl
Flameng, Willem
Holvoet, Paul
Dymarkowski, Steven
Collen, Desire #
Issue Date: Aug-2002
Series Title: Circulation vol:106 issue:9 pages:1140-1146
Abstract: BACKGROUND: Hypercholesterolemia induces functional and structural changes of the microvasculature and reduces coronary flow reserve in humans and experimental animals. The effect of hypercholesterolemia on left ventricular (LV) function in the absence of coronary stenosis is, however, unknown. Our objective was therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal on LV function in the presence of advanced coronary plaques that do not cause stenosis. METHODS AND RESULTS: Twenty-eight minipigs on cholesterol diet for 34 weeks and 16 control pigs were studied. Seven hypercholesterolemic pigs were withdrawn from the diet for 26 weeks. LV function was assessed with cine-MRI, myocardial blood flow with colored microspheres, and capillary density with immunohistochemistry, and microvascular endothelial cell apoptosis with terminal dUTP nick-end labeling staining. Hypercholesterolemia (17+/-8 versus 268+/-150 versus 12+/-10 mg/dL LDL cholesterol, control versus hypercholesterolemic versus cholesterol withdrawal; P<0.001) induced atherosclerosis but not stenosis in the left coronary artery. Baseline cardiac output, ejection fraction, and stroke volume were similar in control and hypercholesterolemic pigs. In dobutamine stress test, cardiac output (P<0.05) and stroke volume (P<0.01) were lower in hypercholesterolemic pigs compared with controls. The impaired response to dobutamine was reversible by dietary cholesterol withdrawal. Hypercholesterolemia reduced endomyocardial coronary flow reserve (P<0.01) and capillary density (P<0.05) and induced capillary endothelial cell apoptosis. Hypercholesterolemic pigs failed to reduce vascular resistance in response to increased LV workload and pharmacological vasodilation. CONCLUSION: LDL hypercholesterolemia in minipigs impaired LV response to dobutamine stress in the absence of coronary stenosis.
URI: 
ISSN: 0009-7322
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cardiology
Atherosclerosis and Metabolism (-)
Experimental Cardiac Surgery
Translational Cell & Tissue Research
Radiology
Molecular and Vascular Biology
Translational MRI (+)
× corresponding author
# (joint) last author

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