Burn-induced subepicardial injury in frog heart: a simple model mimicking ST segment changes in ischemic heart disease

Abstract

To mimic ischemic heart disease in humans, several animal models have been created, mainly in rodents by surgically ligating their coronary arteries. In the present study, by simply inducing burn injuries on the bullfrog heart, we reproduced abnormal ST segment changes in the electrocardiogram (ECG), mimicking those observed in ischemic heart disease, such as acute myocardial infarction and angina pectoris. The "currents of injury" created by a voltage gradient between the intact and damaged areas of the myocardium, negatively deflected the ECG vector during the diastolic phase, making the ST segment appear elevated during the systolic phase. This frog model of heart injury would be suitable to explain the mechanisms of ST segment changes observed in ischemic heart disease.

Fig. 1.

Simultaneous recordings of the electrocardiogram (ECG) and the transmembrane action potential in the bullfrog heart. The top trace shows the ECG with the prominent QRS complexes, although the P and T waves are almost indecipherable. The bottom trace illustrates the action potential of ventricular cardiomyocytes, which consists of five phases including phase 0 (rapid upstroke), 1 (partial repolarization), 2 (plateau), 3 (rapid repolarization) and 4 (resting membrane potential).

Fig. 2.

Induction of subepicardial burn injury and the ECG changes in the bull frog heart. (A) To induce subepicardial burn injuries, a heated glass capillary tube was repeatedly imposed on the ventricular wall adjacent to where the ECG recording electrode was placed. (B) ECG changes before (top) and after the injuries (bottom).

Fig. 3.

Mechanisms of ST segment changes in subepicardial burn injury and ischemic heart disease. (A) Mechanisms of ST segment elevation in subepicardial burn injury. The extracellular concentration of K⁺ ions is elevated around the injured cardiomyocytes (a), which makes their resting membrane potentials significantly higher than those of adjacent intact cells (b). Such difference creates a voltage gradient between the intact and damaged areas of the myocardium during the diastolic phase of the cardiac cycle (b), producing “currents of injury” (white arrows), which arise from the damaged subepicardium and flow towards the intact endocardium. Since the currents flow away from the ECG recording electrode placed adjacent to the burn injury (c), the ECG vector during the diastolic phase shows a negative deflection from the isoelectric line (d, arrows), making the ST segment appear elevated during the systolic phase (d, gray waveform). (B) Directions of the “currents of injury” (white arrows) in ischemic heart disease, such as acute myocardial infarction (a) and angina pectoris (b). a: In acute myocardial infarction, the currents flow away from the ECG recording electrode (pericordial lead) towards the other side of the intact ventricle wall. b: In angina pectoris, the currents arise from the damaged endocardium and flow towards the intact ventricular surface where the ECG recording electrode is placed.