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

Abstract

In our previous studies, by simply inducing burn injuries on bullfrog hearts or partially exposing their surface to high-potassium (K +) solution, we could reproduce a ST segment elevation in the electrocardiogram (ECG), which is a characteristic finding in human ischemic heart disease. In the present study, using our burn-induced subepicardial injury model, we could additionally reproduce "reciprocal" ST segment changes for the first time in frog hearts, mimicking those observed in human acute myocardial infarction. Immunohistochemistry demonstrated markedly decreased Na + /K +-ATPase protein expression in the ventricular surface after the burn injury. The loss of this pump expression in injured cardiomyocytes was thought to be responsible for the creation of "currents of injury" and the subsequent ST segment changes observed in acute myocardial infarction. KEY WORDS: acute myocardial infarction, bullfrog heart, Na + /K +-ATPase expression, reciprocal ST segment change Acute coronary syndrome (ACS, formerly called "ischemic heart disease"), including acute myocardial infarction and unstable angina pectoris, is one of the leading causes of death worldwide [1, 12, 14]. To rapidly diagnose acute myocardial infarction and improve the outcome, the electrocardiogram (ECG) is the most useful test in patients with possible myocardial ischemia [16]. However, not all patients with acute myocardial infarction present typical ECG findings represented by an elevation of the ST segment, which is the interval between the ventricular depolarization and repolarization [13]. Additionally, an elevation of this segment is also observed in other normal or abnormal cardiac conditions, such as early repolarization, right bundle-branch block, left ventricular hypertrophy or pericarditis [9]. "Reciprocal" ST segment change, which is frequently observed in acute anterior or inferior myocardial infarction, is defined as an ST segment depression in leads opposite to those that reflect an ST segment elevation [17]. Since reciprocal ST segment change is specifically noted in acute myocardial infarction, the presence of this change strongly supports its diagnosis [2, 18] and also reflects the extent of myocardial ischemia [6]. In our previous studies, by simply inducing burn injuries on the bullfrog heart or partially exposing the heart surface to high-potassium (K +) solution, we were able to reproduce an ST segment elevation in the ECG, which is a characteristic finding in human ischemic heart disease [7, 11]. Here, using our burn-induced subepicardial injury model, we could reproduce reciprocal ST segment changes in frog hearts for the first time that mimicked those observed in human acute myocardial infarction. By immunohistochemistry, we additionally examined the Na + /K +-ATPase protein expression in burned heart ventricle and revealed the physiological mechanisms underlying the ST segment changes in ECG. Adult male bullfrogs, weighing 450 to 550 g (n=12), were purchased from Ohuchi Shōten (Saitama, Japan). After initial inhalation with...

High-magnesium exposure to bullfrog heart causes ST segment elevation

“…Na + /K + -ATPase is an ion pump, through which sodium (Na + ) ions are actively transported out of the cell and K + ions into the cell [6]. Consistent with our previous results [11,13], immunohistochemistry for Na + /K + -ATPase α-subunit (1:50; Santa Cruz Biotechnology, Inc., Dallas, TX, U.S.A.) revealed this protein expression ubiquitously throughout the cellular membrane of cardiomyocytes (Fig. 3B.…”

“…Regarding the mechanisms that underlie the ST segment elevation, the difference in the resting membrane potential between the high-magnesium exposed-and non-exposed-cardiomyocytes produced the "currents of injury" in the diastolic phase [12]. As we previously demonstrated in our frog heart models with subepicardial burn injuries [9,11] or the partial exposure of high-K + solution [13], the currents deflected the ECG vector negatively during the diastolic phase and made the ST segment look elevated in the systolic phase.…”

“…These findings strongly suggested the involvement of similar pathophysiology to acute myocardial infarction in severe hypermagnesemia. In our previous studies, by simply inducing burn injuries on bullfrog hearts or partially exposing their surface to high-potassium (K + ) solution, we reproduced ECG changes of human ischemic heart disease and revealed their physiological mechanisms [ 9 , 11 , 13 ]. Here, by exposing the surface of frog hearts to high magnesium solution, we could reproduce prominent ST segment changes in ECG as actually observed in patients with severe hypermagnesemia [ 1 , 8 ].…”

“…As we described previously [ 9 , 10 , 11 , 13 ], the frogs were subjected to intramuscular injection of a long-acting anesthetic, ethyl carbamate (0.50 g/kg; Wako Pure Chemical Industries, Ltd., Osaka, Japan) after initial inhalation with isoflurane (Pfizer Inc., New York, NY, USA). Under deep anesthesia, the frog hearts were surgically exposed and the electrical signals were directly recorded by ECG amplifier [ 9 , 10 , 11 , 13 ]. The ECG waveforms were monitored and recorded in a data logger (midi LOGGER HV GL2000, GRAPHTEC Corp., Yokohama, Japan) [ 11 ].…”

“…Under deep anesthesia, the frog hearts were surgically exposed and the electrical signals were directly recorded by ECG amplifier [ 9 , 10 , 11 , 13 ]. The ECG waveforms were monitored and recorded in a data logger (midi LOGGER HV GL2000, GRAPHTEC Corp., Yokohama, Japan) [ 11 ]. To detect the transmembrane action potential, the suction-electrode method was employed as we described previously [ 9 , 10 , 13 ].…”