Cardiovascular Research Advance Access first published online on May 7, 2009
This version [Corrected Proof] published online on June 4, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp140
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Myocardial microvascular function during acute coronary artery stenosis: effect of hypertension and hypercholesterolaemia
1 Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
2 Division of Cardiovascular diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
* Corresponding author. Tel: +1 507 284 4695; fax: +1 507 266 9316. E-mail address: lerman.lilach{at}mayo.edu
Aims: Coronary collateral arteries (CCA) reduce cardiovascular events. We tested the hypothesis that new microvessels that proliferate in early atherosclerosis may be associated with myocardial protection during acute subtotal coronary artery obstruction (CAO).
Methods and results: Acute left anterior descending CAO was induced by a balloon catheter in pigs after 12 weeks of high-cholesterol (HC) diet, renovascular hypertension (HTN), or normal control. Cardiac structure, myocardial perfusion, and functional response to iv adenosine and CAO were studied in vivo using electron beam computed tomography (CT). The intra-myocardial microvessels were subsequently evaluated ex vivo using micro-CT, and myocardial expression of growth factors using immunoblotting. Basal myocardial perfusion and microvascular permeability were similar among the groups, whereas their responses to adenosine were attenuated in HC and HTN. A significant decline in myocardial perfusion in normal pigs during acute CAO was attenuated in HC and abolished in HTN. CAO also elicited an increase in normal anterior wall microvascular permeability (+202 ± 59%, P < 0.05), which was attenuated in HC and HTN (+55 ± 9 and +31 ± 8%, respectively, P < 0.05 vs. normal). Microvascular (<200 µm) spatial density was significantly elevated in HC and HTN, accompanied by increased myocardial growth factor expression.
Conclusion: This study demonstrates that early exposure to the cardiovascular risk factors HC and HTN protects the heart from decreases in myocardial perfusion during acute subtotal CAO. This protective effect is associated with and potentially mediated by pre-emptive development of intra-myocardial microvessels that might serve as recruitable CCA.
KEYWORDS Risk factors; Coronary collateral circulation; Preconditioning
Time for primary review: 8 days
These authors contributed equally to this work.
Present address. University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.