抗组胺药安他唑啉对获得性短 QT 间期综合征和长 QT 间期综合征模型的抗心律失常作用。

Antiarrhythmic effect of antazoline in experimental models of acquired short- and long-QT-syndromes.

机构信息

Division of Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.

Clinic of Exotic Pets, Reptiles, Exotic and Feral Birds, University of Hanover, Bünteweg 2, D-30559 Hanover, Germany.

出版信息

Europace. 2018 Oct 1;20(10):1699-1706. doi: 10.1093/europace/eux383.

DOI:10.1093/europace/eux383

PMID:29377987

Abstract

AIMS

Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS).

METHODS AND RESULTS

Sixty-five rabbit hearts were Langendorff-perfused. Action potential duration at 90% of repolarization (APD90), QT-interval, spatial dispersion (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener pinacidil (1 µM, n = 14) reduced APD90 (-14 ms, P < 0.01), QT-interval (-14 ms, P < 0.01), and ERP (-11 ms, P < 0.01), thus simulating acquired SQTS. Additional infusion of 20 µM antazoline prolonged repolarization. Under baseline conditions, ventricular fibrillation (VF) was inducible in 5 of 14 hearts (10 episodes) and in 5 of 14 pinacidil-treated hearts (21 episodes, P = ns). Antazoline significantly reduced induction of VF (0 episodes, P < 0.05 each). Further 17 hearts were perfused with 100 µM sotalol and 17 hearts with 300 µM erythromycin to induce acquired LQTS2. In both groups, prolongation of APD90, QT-interval, and ERP was observed. Spatial dispersion was increased (sotalol: +26 ms, P < 0.01; erythromycin: +31 ms, P < 0.01). Additional infusion of antazoline reduced DISP (sotalol: -22 ms, P < 0.01; erythromycin: -26 ms, P < 0.01). Torsade de pointes (TdP) occurred in 6 of 17 sotalol-treated (22 episodes, P < 0.05 each) and in 8 of 17 erythromycin-treated hearts (96 episodes P < 0.05 each). Additional infusion of antazoline completely suppressed TdP in both groups (P < 0.05 each). Acquired LQTS3 was induced by veratridine (0.5 µM, n = 17) and similar results were obtained (APD90: +24 ms, P < 0.01, QT-interval: +58 ms, P < 0.01, DISP: +38 ms, P < 0.01). Torsade de pointes occurred in 10 of 17 hearts (41 episodes, P < 0.05 each). Antazoline significantly reduced TdP (2 of 17 hearts, 4 episodes, P < 0.05 each).

CONCLUSION

Antazoline significantly reduced induction of VF in an experimental model of acquired SQTS. In three experimental models of acquired LQTS, antazoline effectively suppressed TdP.

摘要

目的

安他唑啉是一种具有抗心律失常特性的第一代抗组胺药。本研究旨在研究安他唑啉在短 QT 综合征（SQTS）和长 QT 综合征（LQTS）中的潜在电生理效应。

方法和结果

65 只兔心采用 Langendorff 灌流。测量动作电位复极 90%（APD90）、QT 间期、空间离散（DISP）和有效不应期（ERP）。IK、ATP 开放剂匹那地尔（1 μM，n=14）可减少 APD90（-14ms，P<0.01）、QT 间期（-14ms，P<0.01）和 ERP（-11ms，P<0.01），从而模拟获得性 SQTS。额外输注 20 μM 安他唑啉可延长复极。在基线条件下，在 14 只心脏中的 5 只（10 个发作）和在匹那地尔处理的 14 只心脏中的 5 只（21 个发作，P=ns）中可诱导心室颤动（VF）。安他唑啉可显著减少 VF 的诱导（0 个发作，P<0.05）。进一步用 100 μM 索他洛尔和 300 μM 红霉素处理 17 只心脏以诱导获得性 LQTS2。在两组中，均可观察到 APD90、QT 间期和 ERP 的延长。空间离散度增加（索他洛尔：+26ms，P<0.01；红霉素：+31ms，P<0.01）。额外输注安他唑啉可降低 DISP（索他洛尔：-22ms，P<0.01；红霉素：-26ms，P<0.01）。扭转型室性心动过速（TdP）发生在 17 只索他洛尔处理的心脏中的 6 只（22 个发作，P<0.05）和在 17 只红霉素处理的心脏中的 8 只（96 个发作，P<0.05）。两组中额外输注安他唑啉均可完全抑制 TdP（P<0.05）。用veratridine（0.5 μM，n=17）诱导获得性 LQTS3，获得相似结果（APD90：+24ms，P<0.01，QT 间期：+58ms，P<0.01，DISP：+38ms，P<0.01）。在 17 只心脏中的 10 只（41 个发作，P<0.05）中发生 TdP。安他唑啉可显著减少 TdP（17 只心脏中的 2 只，4 个发作，P<0.05）。