| Objective: Atrial electrical remodeling (AER) during rapid atrial pacing (RAP) can be enhanced by high vagal activity. However, vagal effects on AER have not been fully investigated although atropine alone was shown not to impede AER. Vasoactive intestinal peptide (VIP) is co-released with acetylcholine (ACH) in vagal nerve, we hypothesized that VIP may play an important role in vagal stimulation promoted atrial electrical remodeling induced by rapid atrial pacing in dogs.Methods: Tweleve adult mongrel dogs were equally divided in 2 groups: control group and VIP-A group. Dogs were intubated and ventilated with a constant volume-cycled respirator (O2 saturation was kept above 95%). A 6F quadripolar catheter was introduced from the femoral vein and placed in the right atrial appendage (RAA). A 6F decapolar catheter was inserted into the coronary sinus (CS) through the right internal jugular vein. A 6F pigtail catheter was introduced from the right femoral artery and placed in the aortic root. Bilateral vagosympathetic (VS) trunks were decentralized for stimulation. Metoprolol (1 mg/kg initial bolus with a maintenance dose of 0.5 mg.kg-1.h-1 thereafter) was administered for sympathetic blockade. All animals were given VS simulation (20 Hz that caused second degree AV block above or sinus rate slowing of >30 bpm) and rapid atrial pacing (RAP, 400 bpm at right appendage). VIP antagonist, [D-p-Cl-Phe6, Leu17]-VIP was administered through aortic root (0.25μg·kg-1·h-1) in VIP-A group, while saline was injected in control group as control. Atrial effective refractory periods (ERP) and sinus rate were measured in the CS and RAA before RAP and every hour after RAP, 5 hours totally. Ventricular rate was measured in vagal stimulation during RAP on every hour.Results: Before and after 5 hours of RAP and VS stimulation, sinus rate was measured in control group, (104.4±22.4) bpm at baseline; (109.3±26.8) bpm at the first hour, (104.3±27.5) bpm at the second hour; (115.5±26.6) bpm at the third hour; (111.3±25.7) bpm at the fourth hour; (114.4±26.2) bpm at the fifth hour, P>0.05. Ventricular rate was measured in vagal stimulation during RAP, (75.9±16.5) bpm at the first hour; (74.0±15.5) bpm at the second hour; (75.5±14.6) bpm at the third hour; (78.3±15.7) bpm at the fourth hour; (80.3±12.2)bpm at the fifth hour,P>0.05. Before and after 5 hours of RAP, sinus rate was measured in VIP-A group, (121.1±16.4) bpm at baseline; during the first to fifth hour ,ventricular rate was measured respectively (116.6±15.9) bpm; (119.4±18.2) bpm; (118.4±12.5) bpm; (118.3±12.0)bpm; (123.2±14.3) bpm,P>0.05;Ventricular rate was measured in vagal stimulation from first hour to the fifth hour during RAP respectively, (86.6±13.6) bpm; (89.4±12.2) bpm; (87.4±10.5) bpm; (87.3±11.0) bpm; (90.9±12.3) bpm,P>0.05. After 5 hours of RAP and VS stimulation, sinus rate almostly no changed during the experiment, indicating the effect of sympathetic blockade with metoprolol was stable. The ventricular rate during vagal stimulation was significant lower (P<0.05), indicating vagal stimulation was effective. After 5 hours of RAP, VS stimulation resulted in more pronounced ERP shortening. In control group, ERP shortened (-14.5±10.0) ms at the first hour; (-18.4±9.0) ms at the second hour; (-21.9±11.2) ms at the third hour; (-25.4±10.3)ms at the fourth hour; (-25.9±13.1) ms at the fifth hour, P<0.05. In VIP-A group, ERP almost no changed, ERP was (118.5±13.1) ms at baseline; (120.0±11.5) ms after VIP antagonist bolus given, (117.8±13.7) ms at the first hour after RAP, (116.3±14.7) ms at the second hour; (121.4±13.2) ms at the third hour; (118.6±10.6) ms at the fourth hour, (117.6±11.6) ms at the fifth hour, P>0.05. ERP changes at RAA and CS were similar in both groups.Conclusion: [D-p-Cl-Phe6, Leu17]-VIP can inhibit atrial electrical remodeling induced by rapid atrial pacing under VS stimulation. So VIP that is co-released with ACH, may play a very important role in vagal stimulation promoted atrial electrical remodeling induced by rapid atrial pacing in dogs.
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