Individuals suffering from hypertension and cardiac disease can exhibit myocardial hypertrophy and contractile dysfunction as well as a range of electrophysiological and histological changes within the myocardium including interstitial fibrosis, increased myocardial stiffness, decreased heart rate variability and prolonged QT interval. During the progression to cardiac failure, considerable remodelling of the myocardial extracellular matrix is known to occur, although it remains to be determined if these pathologies are due, in part, to increased collagen deposition/decreased collagen degradation, or conversely that changes in the ratio of type I to type III collagens are responsible (Weber, 1989). In this study, we have employed a model of left ventricular hypertrophy (LVH) and heart failure (HF) in the ferret in order to accurately relate changes in collagen turnover with the development of LVH and HF.

All procedures accorded with UK legislation (isoflurane inhalational anaesthesia for surgical procedures; Schedule 1 killing, pentobarbitone 200 mg kg^-1).

Heart failure occurred 8-12 weeks following ascending aortic coarctation, the mean heart/body weight ratio (± S.E.M.) increased from 4.7 ± 0.2 g kg^-1 in sham operated animals, to 9.3 ± 0.5 g kg^-1 in HF (n = 17, P < 0.005 Student’s unpaired t test). ECG data gathered from a subset of animals using telemetry implants showed that the corrected RT interval (used as a measure of the QT interval in this model) increased during the development of LVH and HF by 17 ± 3 % of pre-operative values measured when clinical symptoms of HF were present (n = 3, P < 0.005, paired t test). Furthermore, heart rate variability (measured as the standard deviation of the mean heart rate from sequential 24 h periods) decreased with the onset of heart failure. No such change was observed in sham-operated animals.

Collagen levels in the left ventricular myocardium were determined when clinical symptoms of HF were present using a combination of high performance liquid chromatography (HPLC) and histological analysis. The HPLC data showed that in HF with LV chamber dilatation the mean collagen content per dry weight of tissue was reduced compared to sham operated animals (2.7 ± 0.4 % vs. 4.5 ± 0.5 %, n = 6, P < 0.05, unpaired t test). This decrease in the collagenous matrix of the myocardium may partly explain the observation of left ventricular chamber dilatation during heart failure. It still remains to be determined to what extent changes in myocardial collagen concentration influence the observed changes in heart rate variability and susceptibility to arrhythmias in this model of heart failure.

This work was supported by The British Heart Foundation