Ventricular Dysfunction in Obese and Nonobese Rats with Metabolic Syndrome

Abstract

Obesity and dyslipidemias are both signs of metabolic syndrome, usually associated with ventricular arrhythmias. Here, we tried to identify cardiac electrical alteration and biomarkers in nonobese rats with metabolic syndrome (MetS), and these findings might lead to more lethal arrhythmias than obese animals. The MetS model was developed in Wistar rats with high-sucrose diet (20%), and after twenty-eight weeks were obtained two subgroups: obese (OMetS) and nonobese (NOMetS). The electrocardiogram was used to measure the ventricular arrhythmias and changes in the heart rate variability. Also, we measured ventricular hypertrophy and its relationship with electrical activity alterations of both ventricles, using micro-electrode and voltage clamp techniques. Also, we observed alterations in the contraction force of ventricles where a transducer was used to record mechanical and electrical papillary muscle, simultaneously. Despite both subgroups presenting long QT syndrome ( $0.66\pm 0.05$ and $0.66\pm 0.07$  ms with respect to the $\text{control}0.55\pm 0.1$  ms), the changes in the heart rate variability were present only in OMetS, while the NOMetS subgroup presented changes in QT interval variability (NOMetS $\text{SD}=1.8$ , $\text{SD}2=2.8$ ; $\text{SD}1/\text{SD}2=0.75$ ). Also, the NOMetS revealed tachycardia (10%; $p<0.05$ ) with changes in action potential duration (63% in the right papillary and 50% in the left papillary) in the ventricular papillary which are correlated with certain alterations in the potassium currents and the force of contraction. The OMetS showed an increase in action potential duration and the force of contraction in both ventricles, which are explained as bradycardia. Our results revealed lethal arrhythmias in both MetS subgroups, irrespectively of the presence of obesity. Consequently, the NOMetS showed mechanical-electrical alterations regarding ventricle hypertrophy that should be at the NOMetS, leading to an increase of CV mortality.