非抗心律失常药物的抗心律失常作用.ppt

非抗心律失常药物的抗心律失常作用机制 电重构 离子通道改变 结构重构 钙超载 RAS激活 心肌缺血、凋亡 细胞反分化 心肌张力改变 心肾性疾病 强心利尿 血流动力学异常 血扩剂或正性肌力药 减轻室壁张力 神经内分泌异常 ACEI,?B, 醛固酮拮抗剂 1940s 1960s 1970s 1990s - 2000 Pepper, Arch Intern Med 1999. 心力衰竭治疗观念的演变 心律失常治疗观念的演变？ 谢 谢！ * 不是窦性心律不好，而是药物的副作用抵消了窦律的好处。 * * * 器质性心脏病时非心律失常起源点的心肌细胞对抗心律失常药物的“抵抗力”下降，可能造成新的心律失常起源点。 * By intention-to-treat analysis, the recurrence rate was lower in the amiodarone + irbesartan group. Kaplan-Meier analysis demonstrated a 2-month probability for maintaining sinus rhythm of 85% for irbesartan + amiodarone-treated patients compared with 63% for those taking amiodarone alone (p=0.008).20 * 抗心律失常药物子改变电重构，不能改变结构重构。 * Rate-dependent effects of rapid pacing on mRNA levels of Kv1.5, Kv4.2, and Kv4.3. Top panels, RNase protection assays of Kv1.5, Kv4.2, and Kv4.3 are shown. S indicates sinus rhythm; N, negative control with yeast tRNA. Numbers indicate the pacing rate. Lines and circles represent protected fragments of channel gene and cyclophilin, respectively. From left to right in each top panel, mRNA levels of samples at 2 (Kv1.5), 4 (Kv4.2), and 8 (Kv4.3) hours after onset of pacing are shown at various pacing rates. Increase of Kv1.5 mRNA level and decrease of Kv4.2 and Kv4.3 mRNA levels exhibited rate dependence. Bottom panels, Data of Kv1.5 mRNA at 0.5 and 2 hours after onset of pacing, Kv4.2 at 4 hours, and Kv4.3 at 8 hours are shown as mean±SD (each n=5, *P0.05 vs sinus rhythm). * Electron microscopy of goat atrial myocardium. a, Atrial myocardium from goat in sinus rhythm. Note presence of sarcomeres (s) throughout entire cytosol and presence of normal mitochondria (m) between sarcomeres. b, Severely affected atrial myocardium from goat in chronic atrial fibrillation. Normal sarcomeres (s) are present only at periphery of cells, with residual parts of sarcomeres also present more centrally. Glycogen (gl) has accumulated in sarcomere-depleted areas. Magnification x2000. * Figure 5. Transmission electron micrographs of atrial myocar