Detection of acute cardiac allograft rejection with high resolution electrocardiography: experimental study in rats

To diagnose early acute cardiac rejection, we evaluated high-resolution electrocardiography in rats. Heterotopic heart transplantations were performed in allogeneic animals, either treated with cyclosporine or untreated, and in syngeneic animals. High-amplification electrocardiograms were recorded daily, under anesthesia, with two intra-abdominal leads. After amplification (x 5000 to 20,000), the electrocardiographic signal was acquired and analyzed with P-Clamp software. We measured the amplitude (millivolts) and duration (milliseconds) of the auriculogram (P wave) and the ventriculogram (QRS wave), the duration of auriculoventricular conduction (milliseconds; PQ interval) and the heart rate. Twenty-five grafted hearts were fully studied in recipients not treated with cyclosporine (allogeneic n = 16, syngeneic n = 9).

In the allogeneic group, acute cardiac rejection was always accompanied by an early and progressive increase in P wave duration and PQ interval, whereas an increase in QRS duration was subsequently recorded. No significant change in P wave, PQ interval, or QRS wave duration was recorded in the syngeneic group, which showed no histologic rejection lesions. A decrease in P wave and QRS wave amplitude was recorded in both groups of animals. In the allogeneic group treated with cyclosporine (n = 21), grafted hearts were removed early (4.5 +/- 0.5 days): 10 cardiac grafts were rejected and 11 were not. An increase in P wave duration > or = 20% was associated with mild rejection in most cases. The sensitivity and specificity of this electrocardiographic sign were excellent (100%). The auricular (right and left atria) and the ventricular (right and left ventricles) tissues were evaluated histologically. In the allogeneic groups (n = 26), the histologic lesions during acute rejection were greater in the auricular myocardium than in the ventricular myocardium. Rejection in the atrial and ventricular myocardium was most often differentiated by one degree according to the Billingham classification.

We concluded that acute cardiac rejection in rats is associated with early conduction disturbances in the atrial myocardium which can be shown by high-resolution electrocardiography.