[Expression of HCN4 protein in ventricular outflow tract of rabbit with idiopathic ventricular tachycardia]

Abstract

Objective: To confirm the existence of purkinje fibers in rabbit outflow tract tissue and explore the role of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 4 (HCN4) protein in idiopathic ventricular tachycardia.

Methods: A total of ten New Zealand white rabbits were randomly selected to observe whether there were pukinje fibers in outflow tract by the methods of HE staining and immunohistochemical detection of midsize neurofilament (NF-M). Forty rabbits were randomly divided into four groups: normal control group (SO), ventricular tachycardia group (VT), ventricular tachycardia+ esmolol intervention group (VT+ ESM) and ventricular tachycardia+ ivabradine intervention group (VT+ IVA). Immunohistochemistry was used to detect the expression of HCN4 protein in ventricular outflow tract; the required output voltage amplitude was recorded when ventricular tachycardia was induced; the times and duration of spontaneous ventricular tachycardia when stimulation stopped were also recorded for each group.

Results: (1)Purkinje fibers existed in the myocardial tissue of rabbit outflow tract. (2)HCN4 protein expression significantly increased in VT group compared with SO group (left ventricular: 97.6 ± 16.7 vs 29.0 ± 8.0, P<0.01; right ventricular: 92.7 ± 12.3 vs 26.0 ± 10.8, P<0.01), the expression of HCN4 protein obviously reduced in VT+ IVA group compared with VT group (left ventricular: 32.0 ± 9.4 vs 97.6 ± 16.7, P<0.01; right ventricular: 30.8 ± 12.4 vs 92.7 ± 12.3, P<0.01). (3)The output voltage amplitude required to induce the desired ventricular tachycardia in VT+ ESM group and VT+ IVA group were higher than the VT group, under the same high frequency stimulation (P<0.01); the times and duration of spontaneous ventricular tachycardia in VT+ ESM group and VT+ IVA group significantly reduced when the stimulation stopped, compared with the VT group (both P<0.01).

Conclusions: (1)Purkinje fibers exist in ventricular outflow tract, which may be the histological origin of the ventricular tachycardia. (2)HCN4 protein is up-regulated in ventricular outflow tract when ventricular tachycardia occurs. (3)Esmolol and ivabradine can prevent and reduce the occurrence of ventricular tachycardia, and as the specific inhibitor of the HCN channel, the effect of ivabradine is more obvious.