Wiegerinck Rob F, de Bakker Jacques M T, Opthof Tobias, de Jonge Nicolaas, Kirkels Hans, Wilms-Schopman Francien J G, Coronel Ruben
Experimental Cardiology Group (ECG), Dept. of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands.
Basic Res Cardiol. 2009 May;104(3):321-32. doi: 10.1007/s00395-008-0771-7. Epub 2009 Jan 12.
To investigate ventricular conduction and refractoriness before and after application of rotigaptide, an enhancer of gap junctional conductance, to explanted hearts of patients with heart failure (HF).
In six explanted perfused hearts of patients with end-stage HF, activation/repolarization mapping was performed and refractory periods (RPs) and activation recovery intervals (ARIs) were measured before and after application of 50 nM rotigaptide. Rotigaptide caused a decrease of RP from 476 +/- 36 to 453 +/- 31 ms (P < 0.05), but did not change ARI-dispersion. During premature activation along the fibers rotigaptide decreased the minimal activation time (AT(min)) and maximal activation time (AT(max)) significantly from 35 +/- 12 to 24 +/- 9 and from 97 +/- 38 to 43 +/- 7 ms, respectively. Rotigaptide did not change AT(min) and AT(max) during activation perpendicular to the fiber direction. After application of rotigaptide conduction curves normalized in five/six recordings when activation was parallel, but destabilized in three/six hearts when activation was perpendicular to fiber direction. The destabilization was associated with local conduction delays rather than with facilitation of conduction.
Rotigaptide applied to hearts of patients with end-stage HF shortened RPs normalized conduction curves and increased conduction parallel to fiber direction. However, in 50% of the hearts local slowing of conduction with destabilization of conduction (curves) occurs at sites close to the stimulation site, when activation is perpendicular to fiber direction.
研究缝隙连接电导增强剂罗替加滨应用于心力衰竭（HF）患者离体心脏前后的心室传导和不应期。
在6例终末期HF患者的离体灌注心脏中，进行激活/复极标测，并在应用50 nM罗替加滨前后测量不应期（RPs）和激活恢复间期（ARIs）。罗替加滨使RP从476±36 ms降至453±31 ms（P<0.05），但未改变ARI离散度。沿纤维方向进行早搏激活时，罗替加滨使最小激活时间（AT(min)）和最大激活时间（AT(max)）分别从35±12 ms显著降至24±9 ms以及从97±38 ms显著降至43±7 ms。激活垂直于纤维方向时，罗替加滨未改变AT(min)和AT(max)。应用罗替加滨后，当激活平行时，五/六份记录中的传导曲线恢复正常，但当激活垂直于纤维方向时，三/六例心脏的传导曲线不稳定。这种不稳定与局部传导延迟有关，而非传导易化。
应用于终末期HF患者心脏的罗替加滨缩短了RPs，使传导曲线恢复正常，并增加了平行于纤维方向的传导。然而，当激活垂直于纤维方向时，50%的心脏在靠近刺激部位处出现局部传导减慢和传导（曲线）不稳定。
