title: Bradycardia stimulates vascular growth during gradual coronary occlusion.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Chronic bradycardia during gradual coronary artery occlusion facilitates angiogenesis/arteriogenesis in collateral-dependent myocardium and preserves maximal perfusion.
authors.affiliation: Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA. kathryn-lamping@uiowa.edu
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Lamping
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Dezhi
authors.initials: D
authors.lastname: Xing
authors.forename: Lance P
authors.initials: LP
authors.lastname: Christensen
authors.forename: James
authors.initials: J
authors.lastname: Martins
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tomanek
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology; D001919:Bradycardia / Q000503:physiopathology*; D002196:Capillaries / Q000502:physiology; D002908:Chronic Disease; D003326:Coronary Circulation / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology; D003971:Diastole / Q000502:physiology; D004285:Dogs; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042787:Receptor, TIE-2 / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2