Lin Lung-Chun, Wu Chau-Chung, Lin Mao-Shin, Lin Shien-Fong, Liu Yen-Bin
Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Ultrasound Med Biol. 2009 Feb;35(2):209-18. doi: 10.1016/j.ultrasmedbio.2008.08.019. Epub 2008 Oct 31.
The purpose of this study is to provide direct evidence for the role of intercellular communications in electrical synchronization and mechanical function of myocardium. We used heptanol, a reversible inhibitor of gap junctions, at low (0.16 mM) and high (0.5 mM) concentration as perfusate for 18 Langendorff-perfused rabbit hearts to study its effects on myocardial electrical and mechanical functions. Optical mapping was performed to measure conduction velocity (CV) and action potential duration (APD). Ultrasonic integrated backscatter and Doppler tissue imaging (DTI) were used to evaluate the intrinsic and global myocardial contractile performance. The CV decreased during low-dose heptanol infusion and became much slower at high dose (high dose vs. baseline, 50.8 +/- 10.2 cm/s vs. 69.3 +/- 8.8 cm/s, p < 0.001). After washout of heptanol, CV completely recovered. The alterations of APD by heptanol infusion were similar to CV. The APD dispersion, standard deviation of APD(80), was increased after heptanol infusion (low dose vs. baseline, 5.9 +/- 1.1 ms vs. 4.3 +/- 1.1 ms, p = 0.004; high dose, 6.0 +/- 1.3 ms, vs. baseline, p = 0.035). However, washout did not restore the APD dispersion which became even larger after washout (13.6 +/- 1.9 ms vs. high dose and baseline, both p < 0.001). Regarding contractile function, heptanol treatment resulted in a progressive decrease of cardiac cycle-dependent variations of integrated backscatter (CVIBS; low dose vs. baseline, 6.1 +/- 1.7 dB vs. 7.2 +/- 1.8 dB, p = 0.007; high dose 1.7 +/- 0.3 dB vs. baseline, p < 0.001) and peak systolic strain rate (low dose vs. baseline, -1.5 +/- 0.6 1/s vs. -1.9 +/- 0.6 1/s, p = 0.014; high dose -0.4 +/- 0.2 1/s; vs. baseline, p < 0.001). That both CVIBS and strain rate incompletely recovered after heptanol washout may be attributed to the increased APD dispersion. In conclusion, uncoupling of gap junctions resulted in slowing CV, increased repolarization heterogeneity, reduced CVIBS and impaired myocardial contractility. There was a reversible dose-response relationship between the myocardial electromechanical functions and gap junction coupling.
本研究的目的是为细胞间通讯在心肌电同步和机械功能中的作用提供直接证据。我们使用间隙连接的可逆抑制剂庚醇，以低浓度（0.16 mM）和高浓度（0.5 mM）作为灌注液，对18个Langendorff灌注的兔心脏进行灌注，以研究其对心肌电和机械功能的影响。进行光学映射以测量传导速度（CV）和动作电位持续时间（APD）。使用超声背向散射积分和多普勒组织成像（DTI）来评估心肌的固有和整体收缩性能。低剂量庚醇灌注期间CV降低，高剂量时变得更慢（高剂量与基线相比，50.8±10.2 cm/s对69.3±8.8 cm/s，p<0.001）。庚醇洗脱后，CV完全恢复。庚醇灌注引起的APD改变与CV相似。庚醇灌注后APD离散度，即APD(80)的标准差增加（低剂量与基线相比，5.9±1.1 ms对4.3±1.1 ms，p = 0.004；高剂量，6.0±1.3 ms，与基线相比，p = 0.035）。然而，洗脱并未恢复APD离散度，洗脱后离散度变得更大（13.6±1.9 ms与高剂量和基线相比，p均<0.001）。关于收缩功能，庚醇处理导致与心动周期相关的背向散射积分变化（CVIBS；低剂量与基线相比，6.1±1.7 dB对7.2±1.8 dB，p = 0.007；高剂量对基线，1.7±0.3 dB，p<0.001）和峰值收缩应变率逐渐降低（低剂量与基线相比，-1.5±0.6 1/s对-1.9±0.6 1/s，p = 0.014；高剂量-0.4±0.2 1/s；与基线相比，p<0.001）。庚醇洗脱后CVIBS和应变率均未完全恢复，这可能归因于APD离散度增加。总之，间隙连接去偶联导致CV减慢、复极异质性增加、CVIBS降低和心肌收缩力受损。心肌电机械功能与间隙连接偶联之间存在可逆的剂量反应关系。
