Amitriptyline intoxication is caused by its suicidal or accidental overdose. In the present study, by intravenously injecting 1.5 or 3.0 mg/kg amitriptyline into bullfrogs, we actually revealed that amitriptyline causes the widening of QRS complexes in electrocardiogram (ECG). In simultaneous recordings of the cardiac action potential, amitriptyline decreased the slope of phase 0 in the action potential, indicating the inhibition of the inward sodium currents during this phase. The following treatment with sodium bicarbonate quickly restored the widened QRS complexes in the ECG, demonstrating the counteraction with the sodium channel blockade caused by amitriptyline. The dual recordings of ECG waveforms and the action potential in cardiomyocytes enabled us to demonstrate the mechanisms of characteristic ECG abnormalities caused by amitriptyline intoxication.

Using bullfrog hearts, we previously reproduced a ST segment elevation in electrocardiogram (ECG), mimicking human ischemic heart disease. In the present study, by inducing subepicardial burn injuries on the inferior part of the frog heart ventricle, we could reproduce typical ECG changes observed in human inferior wall myocardial infarction, such as the marked elevation of the ST segments in inferior limb leads (II, III, aVF) and their reciprocal depression in the opposite limb leads (I, aVL). Due to the decrease in Na + /K + -ATPase protein expression, the resting membrane potential of injured cardiomyocytes shifted toward depolarization. Such induced electrical difference between the injured and intact cardiomyocytes was thought to be responsible for the creation of "currents of injury" and the subsequent ST segment changes.