Myocardial microvascular function during acute coronary artery stenosis: effect of hypertension and hypercholesterolaemia.
OBJECTIVE
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).


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 microm) spatial density was significantly elevated in HC and HTN, accompanied by increased myocardial growth factor expression.


CONCLUSIONS
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.
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Xiang-Yang
XY
Zhu
Elena
E
Daghini
Alejandro R
AR
Chade
Daniele
D
Versari
James D
JD
Krier
Kyle B
KB
Textor
Amir
A
Lerman
Lilach O
LO
Lerman
D000241:Adenosine / Q000008:administration & dosage; D000818:Animals; D002199:Capillary Permeability; D003097:Collateral Circulation; D017023:Coronary Angiography; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006937:Hypercholesterolemia / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D034421:Sus scrofa; D014057:Tomography, X-Ray Computed; D055114:X-Ray Microtomography
D000241:Adenosine