This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 25/10/2122    most recent 01.ATV.0000179598.57819.77v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lamping, K. G. Articles by Tomanek, R. J. Search for Related Content PubMed PubMed Citation Articles by Lamping, K. G. Articles by Tomanek, R. J. Pubmed/NCBI databases Substance via MeSH Related Collections Coronary circulation Other Vascular biology Angiogenesis Growth factors/cytokines

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2122.)
© 2005 American Heart Association, Inc.

Vascular Biology

Bradycardia Stimulates Vascular Growth During Gradual Coronary Occlusion

Kathryn G. Lamping; Wei Zheng; Dezhi Xing; Lance P. Christensen; James Martins; Robert J. Tomanek

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.

Correspondence to Kathryn G. Lamping, PhD, VA Medical Center, 601 Highway 6 W, Iowa City, IA 52246. 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.

We tested the hypothesis that chronic bradycardia stimulates growth of the collateral circulation. During coronary artery occlusion, bradycardia enhanced maximal conductance, indices of vascular density, and release of growth factors and their receptors in collateral-dependent myocardium. We conclude that bradycardia facilitates angiogenesis/arteriogenesis to preserve myocardial perfusion.

Key Words: bradycardia • collateral circulation • angiogenesis • arteriogenesis • remodeling • capillaries

This article has been cited by other articles:

				N. A. Hasaneen, S. Zucker, R. Z. Lin, G. G. Vaday, R. A. Panettieri, and H. D. Foda Angiogenesis is induced by airway smooth muscle strain Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L1059 - L1068. [Abstract] [Full Text] [PDF]

				S. Gizurarson, M. Lorentzon, T. Ramunddal, F. Waagstein, L. Bergfeldt, and E. Omerovic Effects of complete heart block on myocardial function, morphology, and energy metabolism in the rat Europace, June 1, 2007; 9(6): 411 - 416. [Abstract] [Full Text] [PDF]