心力衰竭时心室肌电重构机理研究

Most cardiac sudden deaths in heart failure are due to malignant ventricular arrhythmias(VAs). The mechanism of VAs in heart failure is not clear. We hypotheses ventricular electrical remodeling(VER) in heart failure play an important role in genesis of VA. Researching items and results: I. The study of manifestation of VER in heart failure and its role in genesis of VA. Methods :The experimental model were produced by venous injection of adriamycin or by partial ligation of abdominal aorta. The ventricular effective refractory period(ERP), monophasic active potential duration(MAPD) and conducting speed were measured before and after rapid pacing. The after depolarizations(AD) and successful ventricular fibrillation(VF) inducing rate were recorded. Results: There were VER in heart failure ,namely, the ERP and MAPD were prolonged in heart failure, especially after rapid pacing. The VF inducing rate and AD were close related with the VER. II. The study of VER mechanism in heart failure. We found that the changing load had no effect in ERP and MAPD prolongation. But when the SERCA2a were blocked, the VER was intensified and when the L-type Ca2+ channel and Na+/Ca2+ exchanging protein were blocked, the VER were weakened. The Ca2+ concentration, mRNA of SERCA2a, Na+/Ca2+, L-type Ca2+ channel exchanging protein in ventricular myocytes was measure and it was found that the Ca2+ concentration was increased in heart failure especially after rapid pacing. Also, the mRNA of SERCA2a, Na+/Ca2+ exchanging protein, L-type Ca2+ channel were increased. Conclusions: The VER plays an important role in genesis of VA. The mechanism of VER was related with SERCA2a, Na+/Ca2+ exchanging protein, L-type Ca2+ channel...

心衰病人大多死于室性心律失常（VA），其机制尚不清楚。我们前期的研究提示心衰时心室肌电重构在VA的发生中有重要意义。本项目将从心室负荷变化、离子通道功能、肌浆网Ca2+-AT酶及细胞内Ca2+离子活动变化等方面阐明心衰时心室肌电重构的发生机制。这将有助于哉庖还探懈稍ぃ佣乐涡乃ゲ∪说腣A提供新的病理生理学依据。