CLINICAL STUDY
Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering
Piero O. Bonetti, MD*,
Stephanie H. Wilson, MBBS*,
Martin Rodriguez-Porcel, MD*,
David R. Holmes, Jr, MD, FACC*,
Lilach O. Lerman, MD, PhD and
Amir Lerman, MD, FACC*,*
* Division of Cardiovascular DiseasesRochester, Minnesota, USA
Division of Hypertension, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA
Manuscript received February 27, 2002;
revised manuscript received April 18, 2002,
accepted May 7, 2002.
* Reprint requests and correspondence: Dr. Amir Lerman, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
lerman.amir{at}mayo.edu
OBJECTIVES: This study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia.
BACKGROUND: Simvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown.
METHODS: Pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated.
RESULTS: Total and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05).
CONCLUSIONS: These findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering.
|
Abbreviations and Acronyms
| | EBCT | | electron beam computed tomography | | ECG | | electrocardiogram | | HC | | hypercholesterolemia | | HC+S | | hypercholesterolemia and simvastatin therapy | | HDL | | high density lipoprotein | | LDL | | low density lipoprotein | | LVEF | | left ventricular ejection fraction | | LVEDV | | left ventricular end-diastolic volume | | LVESV | | left ventricular end-systolic volume | | LVMM | | left ventricular muscle mass | | MAP | | mean arterial pressure | | MP | | myocardial perfusion | | PI | | permeability index |
|
This article has been cited by other articles:
|
|
|
|
 
G. J. Zoghbi, T. A. Dorfman, and A. E. Iskandrian
The Effects of Medications on Myocardial Perfusion
J. Am. Coll. Cardiol.,
August 5, 2008;
52(6):
401 - 416.
[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]
|
|
|
|
|
|
|
A. Lerman, D. R. Holmes, J. Herrmann, and B. J. Gersh
Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both?
Eur. Heart J.,
April 1, 2007;
28(7):
788 - 797.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Y. Zhu, E. Daghini, A. R. Chade, C. Napoli, E. L. Ritman, A. Lerman, and L. O. Lerman
Simvastatin Prevents Coronary Microvascular Remodeling in Renovascular Hypertensive Pigs
J. Am. Soc. Nephrol.,
April 1, 2007;
18(4):
1209 - 1217.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. P. van de Visse, M. van der Heijden, J. Verheij, G. P. van Nieuw Amerongen, V. W. M. van Hinsbergh, A. R. J. Girbes, and A. B. J. Groeneveld
Effect of prior statin therapy on capillary permeability in the lungs after cardiac or vascular surgery.
Eur. Respir. J.,
May 1, 2006;
27(5):
1026 - 1032.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Iwakura, H. Ito, S. Kawano, A. Okamura, T. Kurotobi, M. Date, K. Inoue, and K. Fujii
Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction
Eur. Heart J.,
March 1, 2006;
27(5):
534 - 539.
[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]
|
|
|
|
|
|
|
M. Rodriguez-Porcel, J. Herrman, A. R. Chade, J. D. Krier, J. F. Breen, A. Lerman, and L. O. Lerman
Long-Term Antioxidant Intervention Improves Myocardial Microvascular Function in Experimental Hypertension
Hypertension,
February 1, 2004;
43(2):
493 - 498.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Wilson, A. R. Chade, A. Feldstein, T. Sawamura, C. Napoli, A. Lerman, and L. O. Lerman
Lipid-lowering-independent effects of simvastatin on the kidney in experimental hypercholesterolaemia
Nephrol. Dial. Transplant.,
April 1, 2003;
18(4):
703 - 709.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rodriguez-Porcel, A. Lerman, J. Herrmann, R. S. Schwartz, T. Sawamura, M. Condorelli, C. Napoli, and L. O. Lerman
Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature
Cardiovasc Res,
April 1, 2003;
58(1):
213 - 221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.O Bonetti, L.O Lerman, C Napoli, and A Lerman
Statin effects beyond lipid lowering--are they clinically relevant?
Eur. Heart J.,
February 1, 2003;
24(3):
225 - 248.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Palinski and C. Napoli
Unraveling Pleiotropic Effects of Statins on Plaque Rupture
Arterioscler Thromb Vasc Biol,
November 1, 2002;
22(11):
1745 - 1750.
[Full Text]
[PDF]
|
|
|
|
