Abstract 1089: Chronic Therapy with Electric Vagus Nerve Stimulation Normalizes mRNA and Protein Expression of Connexin-40, -43 and -45 in Left Ventricular Myocardium of Dogs with Heart Failure
Background: In the heart, gap junctions allow for electrical communication between cardiomyocytes and as such, are essential structures for efficient depolarization and repolarization. Connexins (CNX) are major cardiac gap junction proteins consisting of 3 primary isotypes namely CNX-40, CNX-43 and CNX-45. Decreased expression of CNX is strongly implicated in the pathogenesis of lethal ventricular arrhythmias, a condition well described in patients with heart failure (HF). We previously showed that long-term (3 months) monotherapy with selective electric Vagus nerve stimulation (VNS) (CardioFitTM, BioControl Medical, Ltd.), improves LV function and attenuates LV remodeling in dogs with coronary microembolization-induced HF. This study examined the effects of long-term VNS therapy with the CardioFit system on mRNA and protein expression of CNX-40, -43 and -45 in LV myocardium of the same cohort of dogs.
Methods: RNA was extracted and homogenate was prepared from LV tissue of 7 VNS-treated HF dogs, 6 untreated HF dogs (Controls) and 6 normal (NL) dogs. mRNA expression of CNX-40, -43 and -45 was measured using reverse transcriptase polymerase chain reaction and protein expression was measured by western blotting. Bands were quantified in densitometric units (du).
Results: Data are shown in table⇓. mRNA and protein expression of CNX-40, -43 and -45 decreased significantly in Control dogs compared to NL. Long-term VNS therapy significantly increased mRNA and protein expression of CNX-40, 43, and -45 compared to untreated HF Controls.
Conclusions: Long-term VNS therapy using the CardioFit system significantly increases mRNA and protein expression of CNX-40, -43 and -45 in LV myocardium of dogs with HF. Increased expression of these CNXs following VNS therapy represents an important additional benefit of this form of VNS therapy for the treatment of chronic HF.