Kojodjojo Pipin, Kanagaratnam Prapa, Segal Oliver R, Hussain Wajid, Peters Nicholas S
St. Mary's Hospital, Imperial College, London, United Kingdom.
J Am Coll Cardiol. 2006 Sep 19;48(6):1242-9. doi: 10.1016/j.jacc.2006.04.093. Epub 2006 Aug 28.
This study assessed the effects of carbenoxolone on human myocardial conduction and refractoriness.
Carbenoxolone, an antipeptic ulcer drug, has been shown to reduce gap junctional coupling without affecting cellular ion channels. Gap junctions (GJ) are considered to be determinants of cardiac action potential propagation. The effects of GJ uncoupling in the human heart are unknown.
Right atrial (RA) and ventricular (RV) activation mapping (Carto, Biosense Webster Inc., Diamond Bar, California) was performed during sinus rhythm. Right atrial and RV wavefront propagation velocity (WPV), specifically in the direction of propagation, was determined from these maps using a triangulation method. Refractoriness at multiple RA and RV sites, sinus rhythm cycle length, and AH, PR, QRS, and QT intervals were measured. The protocol was repeated 1 h after oral administration of 100 mg of carbenoxolone.
In 11 patients, WPV was reduced from 79.6 +/- 13.3 cm/s to 57.2 +/- 9.1 cm/s (-27.1 +/- 12.8%, p < 0.001) in RA and from 98.7 +/- 19.8 cm/s to 76.5 +/- 21.7 cm/s (-22.7 +/- 14.1%, p < 0.01) in RV after carbenoxolone. Conduction slowing was more marked in 6 older patients with ischemic heart disease compared with younger subjects with normal hearts (RA -35.1 +/- 5.5% vs. -17.5 +/- 12.7%, p = 0.03; RV -33.8 +/- 5.1% vs. -9.3 +/- 7.7%, p < 0.001). Refractoriness and electrocardiogram parameters remained unchanged.
Carbenoxolone causes a 27% reduction in human RA WPV and 23% in the RV without affecting refractoriness. The slowing of myocardial conduction by carbenoxolone demonstrates the significance of GJ in regulating human myocardial conduction and provides a tool for investigating the effects of GJ uncoupling on human arrhythmogenesis.
本研究评估了甘珀酸对人心肌传导和不应期的影响。
甘珀酸是一种抗消化性溃疡药物，已被证明可减少缝隙连接耦联而不影响细胞离子通道。缝隙连接（GJ）被认为是心脏动作电位传播的决定因素。GJ解耦在人心脏中的作用尚不清楚。
在窦性心律期间进行右心房（RA）和心室（RV）激动标测（Carto，Biosense Webster公司，加利福尼亚州钻石吧）。使用三角测量法从这些标测图中确定右心房和RV波前传播速度（WPV），特别是在传播方向上。测量多个RA和RV部位的不应期、窦性心律周期长度以及AH、PR、QRS和QT间期。在口服100mg甘珀酸1小时后重复该方案。
在11例患者中，服用甘珀酸后，RA的WPV从79.6±13.3cm/s降至57.2±9.1cm/s（-27.1±12.8%，p<0.001），RV的WPV从98.7±19.8cm/s降至76.5±21.7cm/s（-22.7±14.1%，p<0.01）。与心脏正常的年轻受试者相比，6例患有缺血性心脏病的老年患者的传导减慢更为明显（RA -35.1±5.5%对-17.5±12.7%，p = 0.03；RV -33.8±5.1%对-9.3±7.7%，p<0.001）。不应期和心电图参数保持不变。
甘珀酸可使人心房RA的WPV降低27%，心室RV的WPV降低23%，而不影响不应期。甘珀酸导致的心肌传导减慢证明了GJ在调节人心肌传导中的重要性，并为研究GJ解耦对人类心律失常发生的影响提供了一种工具。
