on July 28, 2005
Published online before print July 28, 2005, doi: 10.1161/01.ATV.0000179598.57819.77
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Submitted on April 21, 2005
Accepted on July 1, 2005
Bradycardia Stimulates Vascular Growth During Gradual Coronary Occlusion
Kathryn G. Lamping *;
From the Departments of Internal Medicine (K.G.L., D.X., J.M.), Pharmacology (K.G.L.), and Anatomy and Cell Biology (W.Z., L.P.C., R.J.T.), and the Cardiovascular Center (K.G.L., W.Z., D.X., L.P.C., J.M., R.J.T.), University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City; and the Department of Veterans Affairs (K.G.L., D.X., J.M.), Iowa City, Iowa.
* To whom correspondence should be addressed. E-mail: kathryn-lamping{at}uiowa.edu.
Objective--In cultured endothelium, stretch induces release of growth factors that contribute to angiogenesis. We tested the hypothesis that bradycardia, which prolongs ventricular diastolic filling time and volume, promotes collateral vessel growth.
Methods and Results--An ameroid occluder was placed on coronary arteries of dogs with normal heart rates (AM) or bradycardia (55 bpm; AM+BC). A third group had normal heart rates and no ameroid (control [CON]). Four weeks after occluder placement, myocardial blood flow at rest and maximal vasodilation (adenosine) at equivalent heart rates and vascular morphometry of hearts were measured. In AM dogs, conductance (myocardial flow/diastolic pressure) of collateral-dependent myocardium was similar to collateral-independent myocardium during rest but increased to only one third of CON during maximal vasodilation. In contrast, in AM+BC dogs, conductance was similar in collateral-dependent and -independent regions during maximal vasodilation. Arteriolar length density in collateral-dependent myocardium was 80% greater in AM+BC than AM dogs. Capillary length density in collateral-dependent region of AM dogs was lower than CON but normal in AM+BC dogs. The angiopoietin receptor Tie-2 increased in collateral-dependent regions of AM and AM+BC groups, whereas vascular endothelial growth factor increased in collateral-dependent and -independent regions only in AM+BC dogs.
Conclusion--Chronic bradycardia during gradual coronary artery occlusion facilitates angiogenesis/arteriogenesis in collateral-dependent myocardium and preserves maximal perfusion.
Key words: bradycardia • collateral circulation • angiogenesis • arteriogenesis • remodeling • capillaries
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