Zhong Jing-quan, Zhang Wei, Li Yan, Zhong Ming, Li Duoling, Zhang Cheng, Zhang Yun
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Jinan, China.
Cardiology. 2006;106(1):22-8. doi: 10.1159/000092519. Epub 2006 Apr 6.
It was the aim of this study to investigate the variation in metalloproteinase and tissue inhibitor of metalloproteinase (TIMP) connexin levels during tachycardia-induced cardiomyopathy (TIC).
Canine models of TIC were established by rapid right atrial pacing at 350-400 beats per min for 8 weeks in 11 dogs, with another 6 dogs acting as sham operation group. Echocardiography, left ventricular pressure and its first derivation with time (positive and negative maximum, dp/dt(max) and -dp/dt(max)), as well as intracardiac electrograms were recorded before and after rapid pacing at 1, 4 and 8 weeks. Data were acquired in sinus rhythm. Ultrastructural changes in left ventricular tissue were observed by transmission electron microscope. The relative abundance of matrix metalloproteinase (MMP)-9 and TIMP-1 was studied by immunoblotting.
The following hemodynamic changes were detected after 8 weeks of rapid pacing: the TIC group had decreased dp/dt(max) (p < 0.05), the left ventricular relaxation time constant (tau) was prolonged (p < 0.05), both left ventricular end-diastolic volume and left ventricular end-systolic volume were decreased (p <0.05), left ventricular end-diastolic pressure was significantly increased (p <0.05), and -dp/dt(max) was significantly decreased (p <0.001) compared with the control group; no statistical differences in the left ventricular ejection fraction between weeks 1, 4 or 8 (p >0.05) were observed, but left ventricular ejection fraction was significantly decreased after 1 week of pacing (p < 0.05). The left ventricular end-diastolic volume was increased after 1 week of pacing compared with the control group (24.15 +/- 8.15 vs.11.19 +/- 4.41 ml; p <0.05), as shown by echocardiography. Compared with the control group, MMP-9 was significantly higher (0.217 +/- 2.16 E-02 vs. 0.314 +/- 5.263 E-02; p < 0.001), while TIMP-1 was decreased (0.230 +/- 8.944 E-02 vs. 0.120 +/- 9.258 E-03; p < 0.001).
Ventricular dilatation and systolic dysfunction occurred after 1 week of rapid right atrial pacing. Enlarged and disarrayed fibers and mitochondria with disintegrated crystal and an anarchic pattern were observed. Additionally, moderate dilation of the rough endoplasmic reticulum and intercalated disk discontinuity were seen after 8 weeks of pacing, and MMP-9 was increased and TIMP-1 was decreased after the same time period.
本研究旨在探讨心动过速性心肌病（TIC）期间金属蛋白酶和金属蛋白酶组织抑制剂（TIMP）连接蛋白水平的变化。
11只犬通过以每分钟350 - 400次的频率快速右心房起搏8周建立TIC犬模型，另外6只犬作为假手术组。在快速起搏前、起搏1周、4周和8周后记录超声心动图、左心室压力及其随时间的一阶导数（正负最大值，dp/dt(max)和 -dp/dt(max)）以及心内电图。数据在窦性心律下采集。通过透射电子显微镜观察左心室组织的超微结构变化。通过免疫印迹研究基质金属蛋白酶（MMP）-9和TIMP-1的相对丰度。
快速起搏8周后检测到以下血流动力学变化：TIC组dp/dt(max)降低（p < 0.05），左心室舒张时间常数（tau）延长（p < 0.05），左心室舒张末期容积和左心室收缩末期容积均降低（p < 0.05），左心室舒张末期压力显著升高（p < 0.05），与对照组相比 -dp/dt(max)显著降低（p < 0.001）；在起搏1周、4周或8周时左心室射血分数无统计学差异（p > 0.05），但起搏1周后左心室射血分数显著降低（p < 0.05）。超声心动图显示，与对照组相比，起搏1周后左心室舒张末期容积增加（24.15 ± 8.15 vs. 11.19 ± 4.41 ml；p < 0.05）。与对照组相比，MMP-9显著升高（0.217 ± 2.16 E-02 vs. 0.314 ± 5.263 E-02；p < 0.001），而TIMP-1降低（0.230 ± 8.944 E-02 vs. 0.120 ± 9.258 E-03；p < 0.001）。
快速右心房起搏1周后出现心室扩张和收缩功能障碍。观察到纤维和线粒体增大且排列紊乱，晶体解体且呈无序模式。此外，起搏8周后可见粗面内质网中度扩张和闰盘连续性中断，同一时期后MMP-9升高而TIMP-1降低。
