Ricco Mark L, Hua Fei, Lomonte Dina J, Venator Kurt R, Cerda-Gonzalez Sofia, Gilmour Robert F
Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:4182-5. doi: 10.1109/IEMBS.2009.5333928.
We have shown previously that verapamil reduces the slope of the action potential duration (APD) restitution relation, suppresses APD alternans and converts ventricular fibrillation (VF) into a periodic rhythm. To determine whether these effects result primarily from reduction of the APD restitution slope, as opposed to alteration of calcium dynamics unrelated to restitution, we tested the effects of hypocalcemia ([CaCl2]=31-125 microM) in canine ventricle. At normal [CaCl2] (2.0 mM), the slope of the APD restitution relation was >1, APD alternans occurred during rapid pacing and VF was inducible. During hypocalcemia the slope of the restitution relation remained >1 and the magnitude of APD alternans was unchanged. VF still was inducible and the mean cycle length and the variance of the FFT spectra during VF were not altered significantly. These results suggest that reduction of APD restitution slope, rather than blockade of ICa per se, is responsible for the antifibrillatory effects of verapamil in this model of pacing-induced VF, lending further support to the idea that APD restitution kinetics is a key determinant of VF.
我们之前已经表明,维拉帕米可降低动作电位时程(APD)恢复关系的斜率,抑制APD交替现象,并将心室颤动(VF)转变为周期性节律。为了确定这些效应是否主要源于APD恢复斜率的降低,而非与恢复无关的钙动力学改变,我们在犬心室中测试了低钙血症([CaCl2]=31 - 125微摩尔)的影响。在正常[CaCl2](2.0毫摩尔)时,APD恢复关系的斜率>1,快速起搏期间出现APD交替现象,且可诱发VF。在低钙血症期间,恢复关系的斜率仍>1,APD交替现象的幅度未改变。VF仍可诱发,且VF期间的平均周期长度和FFT频谱的方差无显著改变。这些结果表明,在这种起搏诱发VF的模型中,APD恢复斜率的降低而非ICa本身的阻断是维拉帕米抗纤颤作用的原因,这进一步支持了APD恢复动力学是VF关键决定因素的观点。