Partial exposure of frog heart to high-potassium solution: an easily reproducible model mimicking ST segment changes

Abstract

By simply inducing burn injuries on the bullfrog heart, we previously reported a simple model of abnormal ST segment changes observed in human ischemic heart disease. In the present study, instead of inducing burn injuries, we partially exposed the surface of the frog heart to high-potassium (K+) solution to create a concentration gradient of the extracellular K+ within the myocardium. Dual recordings of ECG and the cardiac action potential demonstrated significant elevation of the ST segment and the resting membrane potential, indicating its usefulness as a simple model of heart injury. Additionally, from our results, Na+/K+-ATPase activity was thought to be primarily responsible for generating the K+ concentration gradient and inducing the ST segment changes in ECG.

Reciprocal ST segment changes reproduced in burn-induced subepicardial injury model in bullfrog heart

“…Na + /K + -ATPase is an ion pump that normally transports sodium (Na + ) ions out of the cell and K + ions into the cell [5]. In frog heart ventricle, consistent with previous findings [11,19], immunohistochemistry for Na + /K + -ATPase α-subunit (1:50; Santa Cruz Biotechnology, Inc., Dallas, TX, USA) demonstrated its ubiquitous expression on the plasma membrane throughout the cardiomyocyte (Fig. 4C left).…”

“…Consistent with our previous findings [11], the normal ECG showed a series of QRS complexes and the following T waves were made before the burn injuries ( Fig. 2A top).…”

“…Based on the Nernst equation [3], this generates a significant difference in the resting membrane potential between the normal and injured cardiac muscles. As we recently demonstrated in frog hearts exposed to high K + solution [11], such an electrical difference in cardiomyocytes would create the "currents of injury", causing the ST segment changes shown in Fig. 3.…”

“…4C left). In our recent study, the pharmacological and functional blockade of this pump activity was deeply associated with the ST segment elevation in the ECG [11], as it generated the K + concentration gradient across the plasma membrane. In the present study, since ST segments were similarly elevated or reciprocally depressed after burn injuries (Fig.…”

“…This functionally inhibits the activity of the Na + /K + -ATPase, which transports the ions ATP-dependently [4,5]. Therefore, such "functional" blockade of this pump activity has been considered to be primarily responsible for the pathology of ischemic heart disease [11]. In our burn injury model, as previously demonstrated in patients with early stage heart failure [15], the degeneration of cardiac muscles almost completely diminished the protein expression of Na + /K + -ATPase (Fig.…”