Remodelling of the cardiac extracellular matrix in an ovine model of ageing and heart failure

University of Cambridge (2008) Proc Physiol Soc 11, PC62

Poster Communications: Remodelling of the cardiac extracellular matrix in an ovine model of ageing and heart failure

M. A. Horn1, H. K. Graham1, M. Hall2, K. M. Dibb1, A. W. Trafford1

1. Unit of Cardiac Physiology, University of Manchester, Manchester, United Kingdom. 2. Cardiothoracic Centre, Broadgreen Hospital, Liverpool, United Kingdom.

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The extracellular matrix (ECM) is a lattice like structure providing support and ensuring correct muscle fibre alignment in the heart. Disruption to either the amount or distribution of the cardiac ECM components would be expected to impact adversely on cardiac mechanics and geometry. The aims of this study were to determine if alterations in the amount of cardiac ECM occur in ageing and whether these changes are similar to those seen in heart failure. An ovine model of ageing and heart failure was used. Under isoflurane inhalational anaesthesia right ventricular endocardial pacing leads were implanted and connected to a cardiac pacemaker. Heart failure was induced in 18 month old sheep by right ventricular tachypacing (3.5Hz). Echocardiography was performed in conscious animals. Following 4 weeks of rapid pacing animals were sacrificed by the intravenous administration of pentobarbitone sodium (200mg/kg). The effects of ageing were determined in animals >8yrs of age. Untreated 18 month old animals served as controls. Following sacrifice tissue samples from the left ventricular free wall (LV) were fixed in 4% paraformaldehyde, embedded in paraffin blocks and stained with picro sirius red. Interstitial collagen was quantified by polarised light microscopy. Data are presented as mean ± SEM and assessed using paired or unpaired Students t-test. All procedures accord with current UK legislation. LV fractional shortening was reduced in both the aged (0.50 ± 0.01) and heart failure groups (0.27 ± 0.02) compared to naïve 18 month old animals (0.65 ± 0.03, n = 5-9 each group, p <0.05). LV end diastolic internal dimensions increased in both ageing (3.21 ± 0.17cm) and heart failure (3.84 ± 0.1 cm) relative to control (2.69 ± 0.12cm, p <0.05). Interstitial collagen content, expressed as percentage tissue area occupied by collagen, increased in ageing (2.3 ± 0.4% vs 1.0 ± 0.1%, n = 5, p < 0.05). A similar increase in interstitial collagen content was observed in CHF (2.1 ± 0.5%, p < 0.05). In summary, ageing and heart failure share common alterations in the properties of the cardiac ECM, most notably the presence of interstitial fibrosis. Additionally, both ageing and heart failure show LV chamber dilatation and reduced contractility. We speculate that the commonality of changes in interstitial collagen composition in ageing and heart failure may indicate cardiac ECM remodelling be an important factor in the predisposition of ageing to the development of heart failure.



Where applicable, experiments conform with Society ethical requirements.

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