Laboratório de Cardiologia Celular e Molecular do Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, CEP 21941-902, Brasil.
Cardiovasc Drugs Ther. 2010 Apr;24(2):121-30. doi: 10.1007/s10557-010-6215-2.
The aim of this study was to investigate the impact of granulocyte-colony stimulating factor (G-CSF) administration on cardiac function of rats with chronic myocardial infarction through two different protocols: high dose short term and low dose long term protocols.
Wistar rats were submitted to MI surgery and after 4 weeks they received recombinant human G-CSF (Filgrastim) or vehicle subcutaneously. We tested the classical protocol (50 microg/kg/day during 7 days) and the long term low dose treatment (four cycles of 5 days of 10 microg/kg/day). Cardiac performance was evaluated before, 4 and 6 weeks after G-CSF injections by electro- and echocardiography, hemodynamic and treadmill exercise test.
All infarcted groups exhibited impaired function compared to sham operated animals. Moreover, all cardiac functional parameter were not different between G-CSF and Vehicle group at resting conditions as well as after treadmill exercise stress test, despite intense white blood cell mobilization in both protocols at all time points. Hypertrophy was not different and infarct size was similar in histological analysis
These data clearly show that G-CSF treatment was unable to restore cardiac function impaired by myocardial infarction either with classical approach or long term low dose administration.
本研究旨在通过两种不同方案(高剂量短期和低剂量长期方案)研究粒细胞集落刺激因子(G-CSF)对慢性心肌梗死大鼠心功能的影响。
Wistar 大鼠接受心肌梗死手术,4 周后接受重组人粒细胞集落刺激因子(非格司亭)或载体皮下注射。我们测试了经典方案(7 天内每天 50μg/kg)和长期低剂量治疗方案(4 个 5 天的 10μg/kg/天周期)。在 G-CSF 注射前、4 周和 6 周通过心电图和超声心动图、血流动力学和跑步机运动试验评估心脏功能。
所有梗死组与假手术组相比,功能均受损。此外,尽管两种方案在所有时间点均引起强烈的白细胞动员,但在静息状态以及跑步机运动应激试验后,G-CSF 组和载体组的所有心功能参数均无差异。两种方案的心肌肥厚程度和梗死面积在组织学分析中无差异。
这些数据清楚地表明,G-CSF 治疗无论是采用经典方法还是长期低剂量给药,均不能恢复心肌梗死后受损的心脏功能。