Long-term ECG trends in atherosclerotic mouse subjects

The double-knockout (dKO) mouse model, with homozygous null encoding for the apoE lipoprotein molecule and SRB-I receptor, shows extremely elevated LDL and severely depressed HDL levels in blood serum. The subjects show 100% mortality by the age of 8 weeks, with accompanying cardiac hypertrophy, reduced ejection fraction and high incidence of atherosclerosis and multiple regions of myocardial infarct noted on necropsy. While these gross observations have been published previously, we now present long-term ECG trends of these subjects. Of specific note in the dKO subjects are the appearance of severe bradycardia during the night and early morning; high-amplitude ultradian rhythm fluctuations relative to wild-type mice; ST-segment elevation and depression; and an array of ECG anomalies ranging from bigeminy to 2nd and 3rd degree heart block. While the dKO mice can, and periodically do, experience self-limited episodes of ventricular tachycardia and subsequent fibrillation, the small size of the heart makes sustained re-entry and fibrillation impossible (in accordance with the critical mass hypothesis). Our study of 11 dKO subjects indicates that these subjects are not suffering a tachyarrhythmic death, but rather a progressive bradyarrhythmia and terminal asystolic cardiac arrest