TACHYCARDIA-INDUCED FAILURE ALTERS CONTRACTILE PROPERTIES OF CANINE VENTRICULAR MYOCYTES

Objective: Rapid cardiac pacing has been used as a model for experimen tally-induced cardiomyopathy. However, its relevance to human heart fa ilure 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 v entricular myocytes from failing hearts. The aim of our study was to e valuate the resemblance between canine pacing-induced and human end-st age heart failure. Methods: Myocytes were isolated from the left ventr icular wall of dogs that were in heart failure after 6 weeks of pacing at 250 beats/min. Cell shortening was measured by edge detection. Res ults: Clinical signs of failure included dyspnea, ascites, and heart d ilatation; the hemodynamic parameters were: LVdP/dt(max) 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 faili ng hearts were longer and thinner than those from controls (form facto r: 0.40 +/- 0.01 vs. 0.47 +/- 0.01, P < 0.001, > 30 cells/heart). With 6 mM Ca2+ and at 0.5 Hz, contraction amplitude was significantly atte nuated in myocytes from failing hearts: 6.6 +/- 0.9% cell shortening v s, 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, co ntraction amplitude showed rate-dependent depression in this animal mo del, whereas features like slowing of contraction and relaxation and r educed sensitivity to thapsigargin, were not reproduced.