Itsuro Kazama

In previous experiments using bullfrog hearts, we successfully replicated both the elevation and reciprocal depression of the ST segment observed in electrocardiograms of human ischemic heart disease. In this study, we induced subepicardial burn injuries in the lateral part of the frog heart ventricle, which allowed us to mimic typical electrocardiographic changes associated with human lateral wall myocardial infarction. These changes included a marked ST segment elevation in the high lateral limb leads (I, augmented Voltage Left; aVL) and reciprocal ST segment depression in the opposite limb leads (III, augmented Voltage Foot; aVF). We surmise that the electrical disparity between injured and intact cardiomyocytes generates currents of injury, leading to the observed ST segment alterations.

Background/Aims: Pregnancy is associated with changes in renal hemodynamics, such as increases in renal blood flow and the glomerular filtration rate (GFR). Angiotensin-converting enzyme 2 (ACE2), a transmembrane glycoprotein involved in vasodilation, also acts as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during coronavirus disease 2019 (COVID-19). Methods: Using rats on pregnancy day 16 and postpartum day 5, we examined the histopathological changes in rat kidneys during and after pregnancy. The expressional changes in renal angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) (Ang (1-7)) were examined, together with those of transmembrane protease serine 2 (TMPRSS2). Results: In pregnant rats, the renal arterioles and venules as well as the glomerular capillaries were markedly dilated, indicating renal vasodilation. Immunohistochemistry demonstrated increased ACE2 and Ang (1-7) expression within the proximal renal tubules during pregnancy, which then returned to the virgin levels in the postpartum period. Additionally, the proximal tubular expression of ACE2 and TMPRSS2 was similarly enhanced during pregnancy. Conclusion: As ACE2 and Ang (1-7) exert vasodilatory properties, they were considered responsible for renal vasodilation and the subsequent increase in GFR. Further, the similar distribution and enhanced expression of ACE2 and TMPRSS2 in the proximal renal tubules during pregnancy suggested their roles in the development of acute kidney injury (AKI) following COVID-19 in pregnancy. This study highlights the physiological and pathological significance of ACE2 during pregnancy.

Ischemia-reperfusion injury is caused by reactive oxygen production after revascularization. It is characterized by elevated ST segments on electrocardiogram (ECG), although the mechanisms remain unknown. In the present study, we reproduced the ST segment changes observed during ischemia-reperfusion injury by exposing bullfrog hearts to hydrogen peroxide (H2O2). The ECG showed a marked elevation of the ST segments, and the action potential in cardiomyocytes demonstrated shortening of its duration. H2O2 exposure did not affect the abundance of KATP channel proteins. However, pharmacological blockade by glibenclamide significantly suppressed H2O2-induced changes in ECG and tended to suppress cardiac action potentials. KATP channel stimulation by H2O2 is thought to be responsible for generating an electrical difference in cardiomyocytes and the subsequent ST segment elevation.

Kazama I. Clin Exp Vaccine Res. 2025 Apr;14(2):185-188. https://doi.org/10.7774/cevr.2025.14.e16