摘要目的 探讨血管活性肠肽拮抗剂[D-p-Cl-Phe6,Leu17]-VIP对快速心房肌电重构的影响.方法 成年杂种犬(12只)分别经右股静脉和颈内静脉穿刺放置导管于右心耳(RAA)和冠状静脉窦导管于冠状静脉窦(CS),经右股动脉放置6F猪尾导管于主动脉根部,全麻机械通气(使血氧饱和度保持在95％以上),下行双侧颈交感-迷走神经干分离.右心耳400次/min高频刺激5h,同时给予双侧颈交感-迷走神经刺激(20 Hz),导致二度房室阻滞以上或窦性心率下降大于30次/min.静脉应用美托洛尔(首次静脉推注1 mg/kg,随之给予0.5 mg·kg-1 ·h-1静脉泵维持)阻断交感神经活性.完全随机分2组:对照组(n=6),经主动脉根部注射生理盐水;实验组(n=6),经主动脉根部首次推注VIP拮抗剂[D-p-Cl-Phe6,Leu17]-VIP 0.5 μg/kg,随后持续注射0.25μg· kg-1 ·h-1;分别在基础状态和心房高频刺激后每小时测量CS及RAA的有效不应期(ERP)、窦性心率及迷走神经刺激时心率.结果 对照组中,基础状态与5h快速心房起搏后窦性心率及交感-迷走神经干刺激时心率差异无统计学意义(P＞0.05);经过5h的高频心房起搏和迷走-交感神经干刺激后心房ERP明显缩短[ERP缩短值分别为1 h(-14.5±10.0)ms,2h(-18.4±9.0)ms,3 h(-21.9±11.2)ms,4 h(-25.4±10.3)ms,5 h(-25.9±13.1)ms,P＜0.05].实验组中,基础状态与高频心房起搏和交感-迷走神经干刺激后1～5h,窦性心率差异无统计学意义(P＞0.05);基础状态下、给予VIP拮抗剂负荷量后、高频心房起搏和迷走-交感神经干刺激后1～5h,ERP没有明显变化(P＞0.05).结论 VIP拮抗剂[D-p-Cl-Phe6,Leu17]-VIP能抑制高频心房起搏和迷走-交感神经干刺激所致的快速心房电重构.

abstractsObjective To determine the effect of [D-p-Cl-Phe6,Leu17]-VIP,a vasoactive intestinal peptide antagonist,on rapid atrial electrical remodeling (AER).Methods Twelve adult mongrel dogs were subject to catheterization in the right atrial appendage (RAA) via the right femoral vein and internal jugular vein as well as in the coronary sinus (CS).The 6 F pigtail catheter was then placed in the aortic root.This was followed by separation of bilateral vagosympathetic (VS) trunks under anesthesia and mechanical ventilation (oxygen saturation maintained 95％ or more).The RAA was subject to high-frequency stimulation (400 Hz) for 5 hours and bilateral VS stimulation (20 Hz),thus resulting in second-degree atrioventricular blockade or a sinus rhythm of 30 beats per minute or less.This entailed the administration of metoprolol (1 mg/kg initial bolus with a maintenance dose of 0.5 mg· kg-1 · h-1 thereafter) for sympathetic blockade.All the dogs were randomly assigned to receive injection of the normal saline (control group,n=6) or [D-p-Cl-Phe6,Leu17]-VIP (0.50 μg· kg-1 initial bolus with a maintenance dose of 0.25 μg· kg-1· h-1 thereafter) via the aortic root (treatment group,n=6).The atrial effective refractory period (ERP),sinus rate and the heart rate upon vagal stimulation of the CS and RAA were measured before and once hourly after RAP.Results The difference in the sinus rhythm and heart rate upon vagal stimulation was unremarkable when comparing the baseline levels with those at 5 hours following RAP (both P＞0.05) in control group.There was a significant reduction in the ERP following high-frequency stimulation and bilateral VS stimulation [(-14.5±10.0) ms,(-18.4±9.0) ms,(-21.9±11.2) ms,(-25.4±10.3) ms and (-25.9±13.1) ms at hours 1,2,3,4 and 5,respectively,P＜0.05] in control group.The difference in the sinus rhythm was unremarkable when comparing the baseline levels with those at 5 hours following RAP (both P＞0.05) in treatment group.There were no marked changes in ERP when comparing the baseline levels with post-treatment levels and those following high-frequency stimulation and bilateral VS stimulation (all P＞0.05).Conclusion [D-p-Cl-Phe6,Leu17]-VIP,inhibits AER which is induced by rapid atrial pacing under VS stimulation.