Bradycardia stimulates vascular growth during gradual coronary occlusion.
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.
Lamping
Kathryn G
KG
Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA. kathryn-lamping@uiowa.edu
Zheng
Wei
W
Xing
Dezhi
D
Christensen
Lance P
LP
Martins
James
J
Tomanek
Robert J
RJ
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
D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2