The linking of angiogenesis to contractile performance and substrate metabolism in the hypertrophied and failing heart

Winter, James (2010). The linking of angiogenesis to contractile performance and substrate metabolism in the hypertrophied and failing heart. University of Birmingham. Ph.D.


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It has been suggested that a failure of angiogenesis (capillary growth) to keep pace with myocyte expansion is the driving force which pushes hypertrophied hearts into a state of failure marked by contractile dysfunction and alterations in the mechanisms governing energy production. The aims of this study were to investigate how alterations in ventricular capillarity affect contractile performance and substrate metabolism in the isolated rat heart. It was hypothesised that, if cardiac contractile performance and substrate utilisation are directly related to ventricular capillarity then methods to alter the number and distribution of capillaries within the ventricle could be utilised to demonstrate this relationship. Treatment regimes were split into those aimed at inducing new capillary growth (e.g. chronic bradycardia and exposure to cold environments) and those aimed at reducing ventricular capillarity (e.g. hypertension and beta-adrenoceptor stimulation). In contrast to previous reports, capillary growth within the ventricle was very limited in animals exposed to a chronic increase in energy demand (e.g. cold environments) and those subjected to extended periods of mechanical stimulation (e.g. bradycardia). Ventricular remodeling appears to accommodate for alterations in the load and/or energy demand without the need for an expansion of the existing capillary network. Experiments conducted in beta-adrenoceptor mediated hypertrophy demonstrate that capillary rarefaction has little effect on cardiac contractile performance and experiments with hypertensive animals show no capillary growth despite the dramatic increase in energy demand placed on the heart in these conditions. In conclusion these data demonstrate surprising plasticity in the response of the myocardium to a number of physiological and pathological stimuli and indicate that adequate compensation occurs without the need for expansion of the existing capillary bed. The limited angiongenic capacity of the myocardium may therefore indicate that the capillary supply of the ventricle is not limiting to the function of the heart.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine
Funders: None/not applicable
Subjects: Q Science > QP Physiology


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