去氫吳茱萸鹼對哺乳動物心臟的電藥理學作用

Electropharmacological Effects of Dehydroevodiamine on Mammalian Hearts

去氫吳茱萸鹼(DeHE)為中藥吳茱萸的有效成分，據大白鼠活體實驗結果證實具有降值勤脈血壓及減緩心來的作用，其心臟作用機轉不清楚。本研究以傳統電生理學研究技術在離體免心竇房結和心室肌，及天竺鼠心室肌進行DeHE之心臟電藥理作用機轉研究。另使用單電極電位固定技術研究DeHE對天竺鼠單一心室細胞離子電流的影響。研究結果顯示，在正常灌注液中，1-30μM DeHE明顯延長心臟竇房結細胞自動周期，減小心舒期電位負值及零級去極化速率，並可引起傳導障礙。DeHE在低濃度(0.1-0.3μM)即對心室肌動作電位第三期再極化有明顯抑制作用；在較高濃度(1-10μM)並可引起早期後去極化現象。以高鉀溶液使心室組織部份去極化後（心舒期電位約－50mV），DeHE雖不再引起早期後去極化，但仍然延長動作電位期間，並抑制緩慢動作電位的去極化速率。在單一天竺鼠心室細胞，1-30μMDeHE明顯抑制鈣離子內流，在停藥30分鐘後仍有部份抑制作用存在。本實驗結果顯示DeHE可能經由減少鈣離子內疏而抑制心臟細胞緩慢動作電位。

Electromechanical effects of dehdroevodiamine chloride (DeHE), an alkaloid isolated from Wu-Chu-Yu (Evodiae frutus), on mammalian atrial and ventricular tissues were studied using electrophysiological technique. In rabbit sinoatrial tissues, 1-30μM DeHE increased the spontaneous cycle length, reduced the maximum diastolic potential, inhibited the rate and amplitude of phase-0 depolarization, and could induce conduction block. In rabbit and guinea pig papillary muscle fibers, DeHE increased significantly the duration of action potential at concentrations (0.1-0.3μM) which did not affect the rate of phase-0 depolarization of fast action potential and the force of contraction. At a concentration of 1μM or higher, DeHE could induce low amplitude early after depolarization near plateau level. When the papillary muscle fibers were depolarized in high [K]0 in the presence of epinephrine, DeHE depressed the upstroke velocity and amplitude of slow response action potential. The effects of DeHE on ionic currents were also studied in single myocytes isolated from guinea pig ventricle using whole-cell patch-clamp technique. DeHE (1-30μM) inhibited significantly the slow inward Ca current. It is suggested that DeHE decreased sinus rate and depressed slow response action potentials through a reduction of Ca current.