Electrocardiographic and Echocardiographic Features of Carnitine-Deficient Animal Model

Abstract

Primary systemic carnitine deficiency (CDSP) is a rare disease that can lead to sudden cardiac death (SCD). Meanwhile, cardiac manifestations had been widely reported in CDSP cases. Researches on phenotype and mechanism are needed imperatively to evaluate the influence of carnitine deficiency on cardiovascular system. We induce an intraperitonealinjected carnitine deficiency mouse model and a transgenic mouse model created by CRISPR/Cas-mediated genome engineering to observe the ECG and echocardiography parameters to explore the cardiac pathophysiological features in carnitine deficiency. In female drug-induced carnitine-deficient mice, the tendency of shortened QTc interval existed in experimental groups compared with the control group (P<0 05). Statistically significant differences in QTc interval existed in low-dose as well as high-dose groups and control (P<0 05). The same rule appeared in heart rate (HR) and T wave duration (P<0 05). After 8 weeks of continuous injection, HR, left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) in low-dose group, HR as well as LVPWd in high-dose group increased significantly compared with the control (all P<0 05). In male drug-induced carnitine deficient mice, the tendency of shortened QTc interval also existed in experimental groups compared with the control group (P<0 05). Statistically significant differences in QTc interval existed in low-dose group and control (P<0 05). Compared with the control, PR interval declined significantly in high-dose group (P<0 05). After 8 weeks of continuous injection, no cardiac functional indexes in experimental groups altered significantly compared with the control (all P>0 05) were found. In transgenic mice, free carnitine (C0) level statistically decreased (P<0 05) compared with the wild-type (WT) mice. There was no statistical difference between mice carried two single heterozygote (P>0 05). However, C0 level between compound heterozygote and single heterozygote was statistically significant (P>0 05). Moreover, there were no significant differences recorded compared with WT in ECG and echocardiography (P>0 05). This study suggested that carnitine deficiency had impact on cardiac function and structure in some situations. We summarized the ECG and echocardiography features of carnitine-deficient mice model and build the first transgenic animal model imitating the pathogenic genotype in human CDSP patients, which provide a foundation for further research on pathophysiological and molecular mechanism.