Effect of hypokalemia and right atrial stretch on atrial arrhythmogenesis with aging

Abstract

Atrial Fibrillation (AF) is the most common sustained arrhythmia, and more than 2.7 million people are living with AF in the United States. The elderly are at greatest risk for AF with prevalence estimated at ~10% in individuals over the age of 80. The aged myocardium is subjected to chronic stretch, and atrial muscle stretch is an established risk factor for atrial arrhythmogenesis. Low potassium levels associate with arrhythmias and increase cardiovascular mortality by up to 10-fold. The goal of this investigation was to test factors leading to changes in rhythm and rate in an aging C57BL/6 mouse model. To test these factors, we used isolated hearts with combined cannulation of the aorta and superior vena cava in a modified right-sided working heart perfusion technique. Hearts of Aged (25-29 month) male (n=12) and female (n=14) C57BL/6 mice were subjected to normal Krebs-Henseleit buffer control conditions (control, 6 mM K+) followed by 30 minutes of right-atrial stretch (12 cmH20 right atrial preload), hypokalemia (2 mM K+), or combined stretch and hypokalemia. Heart rate and incidence of atrial arrhythmias were monitored using right-atrial placement of an intracardiac electrocardiogram. Under control conditions average heart rate across all groups was 248±13 BPM with no incidence of atrial tachycardia, fibrillation, or flutter. There were modest (P>0.05) differences in rate and rhythm with stretch (n=8), but hypokalemia decreased (P=0.001) heart rate by 20% and 4/8 hearts exhibited spontaneous atrial tachycardia/fibrillation/flutter. Hearts with combined hypokalemia and stretch exhibited normal heart rate (97% of control) and 5/10 hearts exhibited spontaneous atrial tachycardia/fibrillation/flutter. Observed atrial arrhythmias were present in hearts of both Aged male mice and Aged female mice. In conclusion, the aged mouse atria exhibit arrhythmias in response to hypokalemia and increases in right-atrial preload under hypokalemic conditions. The aged C57BL/6 mouse model is therefore useful for pre-clinical studies of atrial arrhythmogenesis. JC was funded by 2T32 OD011126 and the project was funded by NIH R01 HL136292 and University of Missouri School of Medicine TRIUMPH award (Domeier) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.