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Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

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Abstract

Angiogenesis and improved left ventricular function as a consequence of long-term bradycardia were first demonstrated in normal hearts, either electrically paced (rabbits, pigs) or treated with a selective sinus blocking drug alinidine (rats). Here we review the evidence that chronic heart rate reduction can have similar effects in the heart with compromised vascular supply, due to either hypertensive or haemodynamic overload hypertrophy (rats, rabbits) or ischaemic damage (rats, rabbits, pigs). Bradycardia induced over several weeks increased capillarity in all hypertrophied hearts, and in border and remote left ventricular myocardium of infarcted hearts. In some, but not all cases, coronary blood flow was improved by heart rate reduction, suggesting enlargement of the resistance vasculature in some circumstances. Cardiac or left ventricular function indices, which were depressed by hypertrophy or ischaemic damage, were preserved or even enhanced by chronic heart rate reduction. The expansion of the capillary bed in the vascularly compromised heart induced by bradycardia may be stimulated by mechanical stretch of the endothelium and/or VEGF activated by chamber dilation and myocyte stretch. The increased number of capillaries and more homogeneous distribution of capillary perfusion would support the better pump function, even in the absence of higher coronary flow. The beneficial impact of chronic heart rate reduction on myocardial angiogenesis and function in cardiac hypertrophy and infarction may be major factor in the success of beta-blockers in treatment of human heart failure.

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Abbreviations

CD:

capillary density

C:F ratio:

capillary-to-fibre ratio

FGF:

fibroblast growth factor

LV:

left ventricle

VEGF:

vascular endothelial growth factor

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Acknowledgements

We would like to thank Dr. M. Milkiewicz for the cell proliferation studies, Mrs. Debbie Ruston for technical assistance with histology, Dr. S. Egginton for measurement of blood oxygen content, and Mr. Paul Townsend for assistance with pig surgery.

Author information

Authors and Affiliations

  1. School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK

    M. D. Brown

  2. Department of Cardiology, University Hospital Trust Selly Oak, Birmingham, UK

    M. K. Davies

  3. Department of Physiology, University of Birmingham, Edgbaston, Birmingham, UK

    O. Hudlicka

Authors
  1. M. D. Brown
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  2. M. K. Davies
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  3. O. Hudlicka
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Corresponding author

Correspondence to M. D. Brown.

Additional information

Correspondence to: Dr. M.D. Brown, School of Sport and Exercise Sciences, University of Birmingham, Birmingham B 15 2TT, UK. Tel: +44-121-4144268; Fax: +44-121-4144121; E-mail: m.d.brown@bham.ac.uk

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Brown, M.D., Davies, M.K. & Hudlicka, O. Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia. Angiogenesis 8, 253–262 (2005). https://doi.org/10.1007/s10456-005-9012-y

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  • DOI: https://doi.org/10.1007/s10456-005-9012-y

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