EXPERIMENTAL STUDY
Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity
Martin Rodriguez-Porcel, MD*,
Amir Lerman, MD*,
Patricia J. M. Best, MD*,
James D. Krier, MS ,
Claudio Napoli, MD, PhD  and
Lilach O. Lerman, MD, PhD
* Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
Division of Hypertension, Mayo Clinic, Rochester, Minnesota, USA
Department of Medicine, University of Naples, Naples, Italy
Department of Medicine-0682, University of California, San Diego, California, USA
Manuscript received June 1, 2000;
revised manuscript received September 5, 2000,
accepted October 12, 2000.
Reprint requests and correspondence: Dr. Lilach O. Lerman, Division of Hypertension, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
lerman.lilach{at}mayo.edu
OBJECTIVES
We intended to study the effect of hypercholesterolemia (HC) on myocardial perfusion and permeability response to increased cardiac demand.
BACKGROUND
Hypercholesterolemia is associated with increased incidence of cardiac events and characterized by impaired coronary vascular function, possibly mediated partly through increased pro-oxidative conditions in plasma and tissue. However, it is yet unclear whether HC is also associated with impaired myocardial perfusion and vascular permeability responses in vivo.
METHODS
For 12 weeks pigs were fed a normal, HC or HC diet supplemented daily with antioxidants (HC + AO, 100 IU/kg vitamin E and 1 g vitamin C). Myocardial perfusion and vascular permeability were measured in vivo using electron beam computed tomography before and after cardiac challenge with intravenous adenosine. Plasma and tissue oxidative status was determined ex vivo.
RESULTS
Plasma cholesterol increased in all cholesterol-fed pigs but was associated with increased markers of oxidative stress only in HC pigs. Myocardial perfusion increased in response to adenosine in normal and HC + AO (+37 ± 13% and +58 ± 22%, respectively, p < 0.05 vs. baseline) but not in HC, whereas vascular permeability index increased only in HC pigs (+ 92 ± 25%, p = 0.002). In HC animals, tissue endogenous oxygen radical scavengers and antioxidant vitamins were depleted and LDL oxidizability enhanced, but both were normalized in HC + AO pigs. Myocardial perfusion response was directly, and permeability inversely, associated with plasma and tissue vitamin concentrations.
CONCLUSIONS
This study demonstrates that experimental HC is associated with blunted myocardial perfusion and increased vascular permeability responses in vivo to increased cardiac demand, which may be partly mediated by a shift in oxidative status.
|
Abbreviations and Acronyms
| | ANOVA | = analysis of variance | | AU | = arbitrary units | | BV | = blood volume | | CT | = computed tomography | | EBCT | = electron beam computed tomography | | HC | = hypercholesterolemia | | HC + AO | = HC plus long-term vitamin supplementation | | LDL | = low density lipoprotein | | LV | = left ventricle | | MTT | = mean transit time | | NO | = nitric oxide | | REM | = relative electrophoretic mobility | | SOD | = superoxide dismutase |
|
This article has been cited by other articles:
|
|
|
|
 
J. Lin, X. Zhu, A. R. Chade, K. L. Jordan, R. Lavi, E. Daghini, M. E. Gibson, A. Guglielmotti, A. Lerman, and L. O. Lerman
Monocyte Chemoattractant Proteins Mediate Myocardial Microvascular Dysfunction in Swine Renovascular Hypertension
Arterioscler Thromb Vasc Biol,
November 1, 2009;
29(11):
1810 - 1816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Zhu, E. Daghini, A. R. Chade, D. Versari, J. D. Krier, K. B. Textor, A. Lerman, and L. O. Lerman
Myocardial microvascular function during acute coronary artery stenosis: effect of hypertension and hypercholesterolaemia
Cardiovasc Res,
July 15, 2009;
83(2):
371 - 380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Osipov, M. P. Robich, J. Feng, R. T. Clements, Y. Liu, H. P. Glazer, J. Wagstaff, C. Bianchi, and F. W. Sellke
Effect of thrombin fragment (TP508) on myocardial ischemia-reperfusion injury in hypercholesterolemic pigs
J Appl Physiol,
June 1, 2009;
106(6):
1993 - 2001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. K. Koh, P. C. Oh, and M. J. Quon
Does reversal of oxidative stress and inflammation provide vascular protection?
Cardiovasc Res,
March 1, 2009;
81(4):
649 - 659.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Zhu, M. D. Bentley, A. R. Chade, E. L. Ritman, A. Lerman, and L. O. Lerman
Early changes in coronary artery wall structure detected by microcomputed tomography in experimental hypercholesterolemia
Am J Physiol Heart Circ Physiol,
September 1, 2007;
293(3):
H1997 - H2003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Daghini, X.-Y. Zhu, D. Versari, M. D. Bentley, C. Napoli, A. Lerman, and L. O. Lerman
Antioxidant vitamins induce angiogenesis in the normal pig kidney
Am J Physiol Renal Physiol,
July 1, 2007;
293(1):
F371 - F381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mannheim, D. Versari, E. Daghini, M. Gossl, O. Galili, A. Chade, V. S. Rajkumar, E. L. Ritman, L. O. Lerman, and A. Lerman
Impaired myocardial perfusion reserve in experimental hypercholesterolemia is independent of myocardial neovascularization
Am J Physiol Heart Circ Physiol,
May 1, 2007;
292(5):
H2449 - H2458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Daghini, E. L. Ritman, and L. O. Lerman
Examine Thy Heart With All Diligence: Evaluation of Cardiac Function Using Fast Computed Tomography
Hypertension,
February 1, 2007;
49(2):
249 - 256.
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Zhu, E. Daghini, A. R. Chade, M. Rodriguez-Porcel, C. Napoli, A. Lerman, and L. O. Lerman
Role of Oxidative Stress in Remodeling of the Myocardial Microcirculation in Hypertension
Arterioscler Thromb Vasc Biol,
August 1, 2006;
26(8):
1746 - 1752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Daghini, A. R. Chade, J. D. Krier, D. Versari, A. Lerman, and L. O. Lerman
Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs
Am J Physiol Regulatory Integrative Comp Physiol,
March 1, 2006;
290(3):
R609 - R615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Versari, E. Daghini, M. Rodriguez-Porcel, K. Sattler, O. Galili, K. Pilarczyk, C. Napoli, L. O. Lerman, and A. Lerman
Chronic Antioxidant Supplementation Impairs Coronary Endothelial Function and Myocardial Perfusion in Normal Pigs
Hypertension,
March 1, 2006;
47(3):
475 - 481.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Rodriguez, B. Nespereira, M. Perez-Ilzarbe, E. Eguinoa, and J. A. Paramo
Vitamins C and E prevent endothelial VEGF and VEGFR-2 overexpression induced by porcine hypercholesterolemic LDL
Cardiovasc Res,
February 15, 2005;
65(3):
665 - 673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Herrmann, S. Samee, A. Chade, M. R. Porcel, L. O. Lerman, and A. Lerman
Differential Effect of Experimental Hypertension and Hypercholesterolemia on Adventitial Remodeling
Arterioscler Thromb Vasc Biol,
February 1, 2005;
25(2):
447 - 453.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gossl, P. E. Beighley, N. M. Malyar, and E. L. Ritman
Role of vasa vasorum in transendothelial solute transport in the coronary vessel wall: a study with cryostatic micro-CT
Am J Physiol Heart Circ Physiol,
November 1, 2004;
287(5):
H2346 - H2351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Chade, M. D. Bentley, X. Zhu, M. Rodriguez-Porcel, S. Niemeyer, B. Amores-Arriaga, C. Napoli, E. L. Ritman, A. Lerman, and L. O. Lerman
Antioxidant Intervention Prevents Renal Neovascularization in Hypercholesterolemic Pigs
J. Am. Soc. Nephrol.,
July 1, 2004;
15(7):
1816 - 1825.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Chade, J. D. Krier, M. Rodriguez-Porcel, J. F. Breen, M. A. McKusick, A. Lerman, and L. O. Lerman
Comparison of acute and chronic antioxidant interventions in experimental renovascular disease
Am J Physiol Renal Physiol,
June 1, 2004;
286(6):
F1079 - F1086.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Zhu, M. Rodriguez-Porcel, M. D. Bentley, A. R. Chade, V. Sica, C. Napoli, N. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman
Antioxidant Intervention Attenuates Myocardial Neovascularization in Hypercholesterolemia
Circulation,
May 4, 2004;
109(17):
2109 - 2115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Chade, M. Rodriguez-Porcel, J. Herrmann, X. Zhu, J. P. Grande, C. Napoli, A. Lerman, and L. O. Lerman
Antioxidant Intervention Blunts Renal Injury in Experimental Renovascular Disease
J. Am. Soc. Nephrol.,
April 1, 2004;
15(4):
958 - 966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Chade, M. Rodriguez-Porcel, J. Herrmann, J. D. Krier, X. Zhu, A. Lerman, and L. O. Lerman
Beneficial Effects of Antioxidant Vitamins on the Stenotic Kidney
Hypertension,
October 1, 2003;
42(4):
605 - 612.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Theilmeier, P. Verhamme, S. Dymarkowski, H. Beck, H. Bernar, M. Lox, S. Janssens, M.-C. Herregods, E. Verbeken, D. Collen, et al.
Hypercholesterolemia in Minipigs Impairs Left Ventricular Response to Stress: Association With Decreased Coronary Flow Reserve and Reduced Capillary Density
Circulation,
August 27, 2002;
106(9):
1140 - 1146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. O. Bonetti, S. H. Wilson, M. Rodriguez-Porcel, D. R. Holmes Jr, L. O. Lerman, and A. Lerman
Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering
J. Am. Coll. Cardiol.,
August 7, 2002;
40(3):
546 - 554.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Krier, M. Rodriguez-Porcel, P. J. M. Best, J. C. Romero, A. Lerman, and L. O. Lerman
Vascular responses in vivo to 8-epi PGF2alpha in normal and hypercholesterolemic pigs
Am J Physiol Regulatory Integrative Comp Physiol,
August 1, 2002;
283(2):
R303 - R308.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. STULAK, A. LERMAN, M. R. PORCEL, J. A. CACCITOLO, J. C. ROMERO, H. V. SCHAFF, C. NAPOLI, and L. O. LERMAN
Renal Vascular Function in Hypercholesterolemia Is Preserved by Chronic Antioxidant Supplementation
J. Am. Soc. Nephrol.,
September 1, 2001;
12(9):
1882 - 1891.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rodriguez-Porcel, J. D. Krier, A. Lerman, P. F. Sheedy II, J. C. Romero, C. Napoli, and L. O. Lerman
Combination of Hypercholesterolemia and Hypertension Augments Renal Function Abnormalities
Hypertension,
February 1, 2001;
37(2):
774 - 780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
