Dietary Cholesterol Affects Sympathetic Nerve Function in Rabbit Hearts

Abstract

In order to assess the effect of hypercholesterolemia on cardiac sympathetic nerve function, New Zealand white rabbits were fed a normal diet (the control group) or one enriched with 0.5% cholesterol [the hypercholesterol (HC) group] for 3 months. Before and after the 3-month diet treatment, we performed serial imaging examinations and analyzed the uptake and washout ratio of ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) from the myocardium by administration of ¹²³I-MIBG through an ear vein. At the end of the experiments, the rabbits were sacrificed, and right ventricular strips were taken from their hearts. The inotropic response of the right ventricular strips to isoproterenol (ISO) and norepinephrine (NE) were evaluated. The cardiac MIBG uptake of the HC group, which was evaluated using the heart to mediastinum ratio, was higher than that of the age-matched control group. However, the washout ratios of ¹²³I-MIBG did not differ statistically between the two groups. On pretreatment with cocaine, NE-enhanced contractility was greater in papillary muscles isolated from the HC group. The concentration-response curve to ISO was shifted to the right in the HC group, compared with that in the control group. In conclusion, hypercholesterolemia in rabbits resulted in an increase in sympathetic nerve density in the myocardium, a decrease in the inotropic response to ISO and an increase in the inotropic response to NE in cocaine-treated myocardium. Both the in vivo and in vitro studies demonstrated the functional significance of neural remodeling induced by hypercholesterolemia.

Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia

“…Our previous studies showed that HC induced significant cardiac nerve sprouting and sympathetic hyperinnervation in both immunocytochemical studies in vitro and 123 I-MIBG imaging in vivo in HC rabbits 1,2. Furthermore, there is an excellent dose–response relationship between serum cholesterol level and nerve density for GAP43(+) and TH(+) nerves 1.…”

Normal 123I‐MIBG uptake areas may be associated with hyperinnervation and arrhythmia risk in phenol model rabbit hearts

“…Significant upregulation of these markers has also been reported in a rabbit model with marked hypercholesterolemia . Once hyperinnervation begins, the incidence of VF was enhanced due to an increase in voltage‐gated Ca current, prolongation of action potential duration, and enlarged dispersion of repolarization time …”