개흉견에서 자율신경계가 심실세동의 역치 및 동력학에 미치는 영향 = Change of Electrical Restitution Kinetics and Ventricular Fibrillation Threshold during Direct Autonomic Stimulation in Canine Heart

다국어 초록 (Multilingual Abstract)

Background and Objectives：It is known that ventricular fibrillation (VF) can be enhanced by sympathetic activityand antagonized by vagal activity, and that the kinetics of electrical restitution is a key determinant of VFinduction or maintenance. However, little is known about the effects of autonomic stimulation on electricalrestitution. Therefore, we studied the effect of sympathetic (SS) and vagus nerve stimulation (VS) on the electricalrestitution and VF induction. Materials and Methods：A monophasic action potential (MAP) was simultaneouslyrecorded from the endocardium and epicardium of the left ventricle in 12 open chest canine hearts. The restitutionkinetics were studied using a single ventricular extra-stimuli (S2), following a 15 beat drive train (300 ms), downto the effective refractory period (ERP). S2-MAPD was plotted against the preceding diastolic intervals, fitted toexponential curves and the maximum restitution slope (Smax) measured. The VF threshold (VFT) was determinedas the minimum current that would induce VF with rapid pacing (50×50 ms). Parameters were studiedat the baseline (control) and separately during VS and SS. Results：SS increased the Smax of the endocardium(1.14±0.37 vs. 0.80±0.25, p<0.001), but not that of the epicardium, and also increased the transmural dispersionof Smax and decreased the VFT (1.8±1.3 mA vs. 3.4±1.6 mA, p<0.05), even without significantshortening of the ERP, but VS had the opposite effects. There was a significant correlation between the endocardialSmax, transmural dispersion of the Smax and the VFT, respectively (r=-0.64, p<0.001 and r=-0.531,p=0.003). Conclusion：The role of the autonomic nervous system in ventricular arrhythmogenesis is by means ofelectrical restitution kinetics modulation.

국문 초록 (Abstract)

배경 및 목적：활동전위기간 상환(action potential duration restitution)관계가 심근의 전기 생리학적 불안정성 여부를 결정짓는 매우 중요한 지표이다. 자율신경계가 부정맥, 특히 심실의 빈맥성 부정맥발생에 중요한 역할을 한다는 것은 익히 알려져 있으나, 심장에서 자율신경계가 어떤 기전으로 심실세동의 발생과 유지를 억제 또는 유발하는가는 명확히 밝혀지지 않다. 본 연구의 목적은 교감 및 부교감 신경계가 심근의 전기생리학적 변화와 심실 빈맥성 부정맥의 발생에 미치는 영향을 관찰하고, 심실의 전기적 상환현상에 미치는효과를 조사하여 심실세동의 유발정도의 차이를 전기적 상환현상이론으로 설명하고자 하였다.방 법：실험 동물로는 건강한 한국산 잡견 12마리를 암수 구별없이 사용하였다. 자율신경 자극 중 혈압과 심박동수의 변화, 그리고 단상활동전위기간 측정용 전극을 이용해 심내막과 심외막에서 동시에 활동전위기간을 측정하였다. 심실조율(300 ms) 중 심실 유효불응기를 측정하였고, 활동전위기간의 90%값(APD90)과 확장기 기간(diastolic interval: DI)으로 활동전위기간 상환 곡선(action potential duration restitutioncurve)을 작성하였다. 기저상태와 교감신경 및 미주신경 자극 시 최대 상환곡선 기울기(maximal restitutionslope: Smax)를 구하여 비교하였다. 기저상태와 미주신경 및교감신경 자극시 급속 심박조율(50회×50 ms)을 통해 심실세동을 유발하여, 심실세동 발생 역치(ventricular fibrillationthreshold: VFT)를 측정하였다.
결 과：
활동전위 상환곡선의 Smax는 심내막에서 기저상태에 비해 미주신경 자극시 유의하게 감소(0.49±0.16 vs. 0.80±0.25,p<0.001)되었고, 교감신경 자극시에는 유의하게 증가하였다 (1.14±0.37 vs. 0.80±0.25, p<0.001). 급속 심박조율에 의한 심실세동 유발 역치는 기저상태에서 보다 미주신경 자극시에 평균 5.0±2.3 mA로 유의하게 증가하였으며(p<0.05),성상 신경절 자극시에는 평균 1.8±1.3 mA로 유의하게 감소되었다(p<0.05). 심내막에서 측정한 활동전위 상환곡선의Smax와 심실세동 유발역치 사이에 유의한 상관관계(r=-0.64,p<0.001)가 관찰되었다.결 론：자율신경계의 심실 빈맥성 부정맥의 발생과 유지에 대한 조절기전은 활동전위기간 상환곡선의 기울기 등으로 도식화 할 수 있는 심근의 동적 복원성(dynamic electrical restitution kinetics)의 조절을 통해 관여한다는 것을 알 수 있었다.

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