What is the clinical evidence from this study?

Study design: Other. Population: Tachycardia-induced heart failure. Intervention: Rapid cardiac pacing vs. Control dogs. Primary outcome: Contraction amplitude (cell shortening) with 6 mM Ca2+ and at 0.5 Hz (p=< 0.05).

September 1, 1996Open Access

Tachycardia-induced failure alters contractile properties of canine ventricular myocytes

Q: What are the key findings of this study?

Canine pacing-induced heart failure significantly attenuated myocyte contraction amplitude compared to controls (6.6% vs. 10.0% cell shortening; P<0.05), mimicking rate-dependent depression in humans.

Key Result

Canine pacing-induced heart failure significantly attenuated myocyte contraction amplitude compared to controls (6.6% vs. 10.0% cell shortening; P<0.05), mimicking rate-dependent depression in humans.

Structured PICO

Does rapid cardiac pacing-induced heart failure alter the contractile properties of canine ventricular myocytes compared to controls?

Population

Canine ventricular myocytes from dogs with heart failure induced by 6 weeks of pacing at 250 beats/min, and 6 control dogs

Intervention

Rapid cardiac pacing (250 beats/min for 6 weeks) to induce heart failure

Comparator

Unpaced control dogs

Outcome

Contractile properties (cell shortening, contraction amplitude, time-to-peak contraction, time-to-50% relaxation) in response to graded increases in frequency and calciumsurrogate

The canine pacing-induced heart failure model reproduces the rate-dependent depression of contraction amplitude seen in human failing hearts, but does not replicate the slowing of contraction/relaxation or reduced thapsigargin sensitivity.

Main Result

Absolute Event Rate: 6.6% vs 10%

p-value: p=< 0.05

Limitations

Features like slowing of contraction and relaxation and reduced sensitivity to thapsigargin were not reproduced

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 (from factor: 0.40 +/- 0.01 vs. 0.47 +/- 0.01, P 30 cells/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.