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Tachycardia-induced failure alters contractile properties of canine ventricular myocytes

Ursula Ravens, Kerry Davia, Crispin H. Davies, Peter O'Gara, Angela J. Drake-Holland, John W. Hynd, Mark I.M. Noble, Sian E. Harding
DOI: http://dx.doi.org/10.1016/S0008-6363(96)00121-6 613-621 First published online: 1 September 1996

Abstract

Objective: Rapid cardiac pacing has been used as a model for experimentally-induced cardiomyopathy. However, its relevance to human heart failure is not clear at present because little is known about changes in size and function of ventricular myocytes. We have therefore studied the responses to graded increases in frequency and calcium in canine ventricular myocytes from failing hearts. The aim of our study was to evaluate the resemblance between canine pacing-induced and human end-stage heart failure.Methods: Myocytes were isolated from the left ventricular wall of dogs that were in heart failure after 6 weeks of pacing at 250 beats/min. Cell shortening was measured by edge detection.Results: Clinical signs of failure included dyspnea, ascites, and heart dilatation; the hemodynamic parameters were: LVdP/dtmax 1613 ± 149 vs. 4713 ± 304 mmHg/s in 6 control dogs; LVEDP 17.2 ± 4.4 vs. 5.6 ± 1.1 mmHg; LV volume 60.5 ± 6.2 vs. 30–35 ml. Myocytes from failing hearts were longer and thinner than those from controls (form factor: 0.40 ± 0.01 vs. 0.47 ± 0.01, P < 0.001,>30cells/heart). With 6 mM Ca2+ and at 0.5 Hz, contraction amplitude was significantly attenuated in myocytes from failing hearts: 6.6 ± 0.9% cell shortening vs. 10.0 ± 0.8% in controls (P < 0.05). This deficit was exacerbated at higher stimulation rates. Time-to-peak contraction and time-to-50% relaxation were not altered. There was no difference in sensitivity to thapsigargin.Conclusion: As with cells from human failing hearts, contraction amplitude showed rate-dependent depression in this animal model, whereas features like slowing of contraction and relaxation and reduced sensitivity to thapsigargin, were not reproduced.

Keywords
  • Frequency responses
  • Postextrasystolic potentiation
  • Heart failure
  • Contractile function
  • Tachycardia
  • Thapsigargin
  • Dog, ventricular myocytes