ALTEX :: Alternatives to Animal Experiments

2001, VOLUME 1

A New High Resolution ECG Technique for Cardiac Conduction and Refractoriness Measured with in vitro Perfused Mice Hearts

Andreas Lueger, Gerhard Stark, Marianne Brodmann and Helmut A. Tritthart

Department of Internal Medicine, Inst. of Medical Physics and Biophysics, Karl-Franzens-Universität A-Graz

INTRODUCTION

Increasing numbers of genetically altered mice models are being developed for a better understanding of mechanisms underlying complex cardiovascular disorders. We describe the evaluation of electrophysiologic parameters from the intact cardiac conduction and pacemaker system of isolated mice hearts perfused by the method of Langendorff. Intracardiac signals could hitherto not be measured in very small hearts, catheters and experiments with larger animals (dogs, swine) were necessary.

METHODS

17 adult mice of either sex were sacrificed by dislocation of the neck. The thorax was quickly opened, the aorta was connected to a cannula and perfused retrograde with Tyrodeīs solution at a constant flow rate. Two silver wire electrodes were placed on the right atrium for recording of atrial signals, two other electrodes were placed in the valve plane for ventricular and HIS-signal recording. Atrial (A-ERP), AV-nodal (AV-ERP) and ventricular effective refractory period (V-ERP) were evaluated using a standard stimulation protocol.

RESULTS

Spontaneous sinus rate was 306±42 beats/min (values are mean ± SEM), AH, HV, QRS and QT intervals were 21.1±3.3, 6.0±0.8, 19.1±3.7 and 119±21 ms respectively. A-ERPīs evaluated under different S1-S1(60,80,100 ms) intervals were 33.0±12.3, 32.4±7.3, 30.1±7.5 ms. AV-ERPīs evaluated under different S1-S1(120, 140, 160 ms) intervals were 76.5±11.5, 72.6±8.4, 70.0±7.4 ms. V-ERPīs evaluated under different S1-S1(80, 120, 160 ms) intervals were 45.2±12.8, 42.5±13.4, 41.1±12.8 ms. In contrast to the ERPīs of the AV-node no clear rate adaptive phenomenon of the atrial and ventricular ERPīs could be estimated.

CONCLUSION

The loss of the rate adaptive phenomenon of refractoriness in the mice heart may be explained by an altered composition of potassium channels compared to other (larger) species. The isolated mice heart perfused by the method of Langendorff is a reliable way for evaluation of electrophysiological parameters, also in genetically altered mice models.