CAJ | 학술논문

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.
목적 탐토혈관활성장태길항제[D-p-Cl-Phe6,Leu17]-VIP대쾌속심방기전중구적영향.방법 성년잡충견(12지)분별경우고정맥화경내정맥천자방치도관우우심이(RAA)화관상정맥두도관우관상정맥두(CS),경우고동맥방치6F저미도관우주동맥근부,전마궤계통기(사혈양포화도보지재95％이상),하행쌍측경교감-미주신경간분리.우심이400차/min고빈자격5h,동시급여쌍측경교감-미주신경자격(20 Hz),도치이도방실조체이상혹두성심솔하강대우30차/min.정맥응용미탁락이(수차정맥추주1 mg/kg,수지급여0.5 mg·kg-1 ·h-1정맥빙유지)조단교감신경활성.완전수궤분2조:대조조(n=6),경주동맥근부주사생리염수;실험조(n=6),경주동맥근부수차추주VIP길항제[D-p-Cl-Phe6,Leu17]-VIP 0.5 μg/kg,수후지속주사0.25μg· kg-1 ·h-1;분별재기출상태화심방고빈자격후매소시측량CS급RAA적유효불응기(ERP)、두성심솔급미주신경자격시심솔.결과 대조조중,기출상태여5h쾌속심방기박후두성심솔급교감-미주신경간자격시심솔차이무통계학의의(P＞0.05);경과5h적고빈심방기박화미주-교감신경간자격후심방ERP명현축단[ERP축단치분별위1 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].실험조중,기출상태여고빈심방기박화교감-미주신경간자격후1～5h,두성심솔차이무통계학의의(P＞0.05);기출상태하、급여VIP길항제부하량후、고빈심방기박화미주-교감신경간자격후1～5h,ERP몰유명현변화(P＞0.05).결론 VIP길항제[D-p-Cl-Phe6,Leu17]-VIP능억제고빈심방기박화미주-교감신경간자격소치적쾌속심방전중구.
Objective 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.