Tse James, Gandhi Ankur, Yan Lin, He Yi Qi, Weiss Harvey R
Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA.
J Cardiothorac Vasc Anesth. 2003 Aug;17(4):486-90. doi: 10.1016/s1053-0770(03)00154-x.
To investigate whether triiodothyronine pretreatment enhanced beta-adrenergic responses in stunned myocardium and whether this acute effect of triiodothyronine was mediated through the cyclic adenosine 3',5'-monophosphate (AMP) system.
A prospective study.
University laboratory.
Rabbits.
Rabbit ventricular myocytes were isolated and placed in a medium equilibrated with either air (control) or with 95% N(2) and 5% CO(2) (stunned) for 15 minutes at 37 degrees C. The stunned myocytes were reoxygenated with air for 30 minutes. Triiodothyronine (10 nmol/L) and/or isoproterenol (0.1 nmol/L) was added to the myocytes. Myocyte shortening was measured by using a video-edge detector.
In electrically stimulated cells, the basal values of the percent shortening (22%-30%) and the maximum rate of shortening (22%-25%) were significantly reduced in the stunned myocytes. Isoproterenol (5 minutes) alone significantly increased the percent shortening in the control (from 3.70 +/- 0.36 to 4.14 +/- 0.37) but not in the stunned myocytes (from 2.60 +/- 0.30 to 3.15 +/- 0.27). Triiodothyronine (5 minutes) alone significantly increased the percent shortening in the control (from 3.75 +/- 0.36 to 4.34 +/- 0.45) and in the stunned myocytes (from 2.91 +/- 0.2 to 3.85 +/- 0.26). After triiodothyronine pretreatment for 5 minutes, isoproterenol caused greater increases in the percent shortening in both the control (37%) and the stunned myocytes (62%) than either agent alone. Isoproterenol or triiodothyronine caused small increases in the maximum rate of shortening in the control (14%-16%) and the stunned myocytes (34%-49%). After triiodothyronine pretreatment, isoproterenol caused greater increases in the maximum rate of shortening in both groups (control: 41%, stunned: 73%) than either agent alone. Isoproterenol caused an increase in the level of cyclic AMP (rho;moles/10(5) myocytes) in the control (from 2.92 +/- 0.47 to 3.77 +/- 0.43) but not in the stunned myocytes (from 2.42 +/- 0.25 to 2.42 +/- 0.20). Triiodothyronine pretreatment did not cause any change in cyclic AMP levels in the control (2.50 +/- 0.29) or in the stunned myocytes (2.60 +/- 0.40). After triiodothyronine pretreatment, isoproterenol caused a small increase in the cyclic AMP level in the control but not in the stunned myocytes.
The data showed that the myocardial beta-adrenergic responses were more sensitive to ischemic insult than the triiodothyronine responses. Triiodothyronine pretreatment enhanced beta-adrenergic responses in both the control and the stunned myocytes. However, this acute positive inotropic effect of triiodothyronine might not be mediated through the cyclic AMP system.
研究三碘甲状腺原氨酸预处理是否能增强顿抑心肌中的β-肾上腺素能反应，以及三碘甲状腺原氨酸的这种急性效应是否通过环磷酸腺苷（AMP）系统介导。
一项前瞻性研究。
大学实验室。
兔子。
分离兔心室肌细胞，在37℃下将其置于用空气（对照）或95% N₂和5% CO₂平衡的培养基中（顿抑）15分钟。顿抑的肌细胞再用空气复氧30分钟。向肌细胞中加入三碘甲状腺原氨酸（10 nmol/L）和/或异丙肾上腺素（0.1 nmol/L）。使用视频边缘检测器测量肌细胞缩短情况。
在电刺激的细胞中，顿抑肌细胞的缩短百分比（22% - 30%）和最大缩短速率（22% - 25%）的基础值显著降低。单独使用异丙肾上腺素（5分钟）可显著增加对照组的缩短百分比（从3.70±0.36增加到4.14±0.37），但对顿抑肌细胞无此作用（从2.60±0.30增加到3.15±0.27）。单独使用三碘甲状腺原氨酸（5分钟）可显著增加对照组的缩短百分比（从3.75±0.36增加到4.34±0.45）以及顿抑肌细胞的缩短百分比（从2.91±0.2增加到3.85±0.26）。三碘甲状腺原氨酸预处理5分钟后，异丙肾上腺素使对照组和顿抑肌细胞的缩短百分比增加幅度均大于单独使用任一药物（对照组增加37%，顿抑肌细胞增加62%）。异丙肾上腺素或三碘甲状腺原氨酸使对照组（14% - 16%）和顿抑肌细胞（34% - 49%）的最大缩短速率有小幅增加。三碘甲状腺原氨酸预处理后，异丙肾上腺素使两组的最大缩短速率增加幅度均大于单独使用任一药物（对照组增加41%，顿抑组增加73%）。异丙肾上腺素使对照组的环磷酸腺苷水平（ρ；摩尔数/10⁵个肌细胞）升高（从2.92±0.47升高到3.77±0.43），但对顿抑肌细胞无此作用（从2.42±0.25升高到2.42±0.20）。三碘甲状腺原氨酸预处理对对照组（2.50±0.29）或顿抑肌细胞（2.60±0.40）的环磷酸腺苷水平无任何影响。三碘甲状腺原氨酸预处理后，异丙肾上腺素使对照组的环磷酸腺苷水平有小幅升高，但顿抑肌细胞无此变化。
数据表明心肌β-肾上腺素能反应比三碘甲状腺原氨酸反应对缺血损伤更敏感。三碘甲状腺原氨酸预处理增强了对照组和顿抑肌细胞中的β-肾上腺素能反应。然而，三碘甲状腺原氨酸这种急性正性肌力作用可能不是通过环磷酸腺苷系统介导的。
