Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain):: an echocardiographic study
Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain):: an echocardiographic study
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DOI：
10.1016/s0020-7519(01)00320-4
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发表时间：
2002-02-01
影响因子：
4
通讯作者：
Tanowitz, HB
中科院分区：
文献类型：
--
作者：
Chandra, M;Shirani, J;Tanowitz, HB
维拉帕米已被证明可以减轻慢性克氏锥虫感染小鼠模型的心肌损伤程度。用维拉帕米治疗的感染小鼠的心肌中诱导型一氧化氮合酶和细胞因子的表达显着降低，尸检时炎症浸润和肌细胞坏死也显着减少。在本研究中，我们使用连续经胸超声心动图检查了感染克氏锥虫巴西株的CD I小鼠中维拉帕米治疗的心脏结构和功能相关性。有四组：未感染-未治疗对照、未感染-维拉帕米-治疗、感染-未治疗对照。并接受感染维拉帕米治疗。从感染之日起，连续给予维拉帕米（I gm，11）于饮用水中，总共 120 天。在基线、注射后 40 天和 150 天对小鼠进行评估。与感染维拉帕米治疗组的小鼠相比，未经治疗的感染组小鼠的左心室壁变薄（0.84 +/- 0.02-vs-0.92 +/- 0.04，P < 0.05 mm）。左心室舒张末期直径增加（3.27 +/- 0.15-vs-2.74 +/- 0.05 mm。P < 0.05），缩短百分比减少（37 +/- 2-vs-53 +/- 4%，P < 0.05）。在未感染的未治疗组和未感染的维拉帕米治疗组中，这些参数没有差异。此外，与感染维拉帕米治疗组相比，感染未治疗组小鼠的右心室扩张更严重（视觉等级1.9+/-0.4-vs-1.0+/-0.2，P<0.05）。尸检时，根据组织学测定，感染的未治疗小鼠的心肌损伤程度明显更大。这些数据为先前观察到的维拉帕米在慢性恰加斯心肌病中的心脏保护作用提供了心脏结构和功能的相关性。 (C) 2002 年澳大利亚寄生虫学协会。由 Elsevier Science Ltd 出版。保留所有权利。
Verapamil has been shown to attenuate the extent of myocardial injury in murine models of chronic Trypanosoma cruzi infection. Infected mice treated with verapamil have significantly lower myocardial expression of inducible nitric oxide synthase and cytokines and substantially less inflammatory infiltrate and myocyte necrosis at necropsy. In the present study, we examined the cardiac structural and functional correlates of verapamil treatment in CD I mice infected with the Brazil strain of T. cruzi using serial transthoracic echocardiography. There were four groups: uninfected- untreated control, uninfected-verapamil-treated, infected-untreated control. and infected-verapamil-treated. Verapamil was given in drinking water (I gm,11) continuously from the day of infection for a total of 120 days. Mice were evaluated at baseline, 40 and 150 days p.i. Mice in the untreated-infected group compared with the mice in the infected-verapamil-treated group showed thinning of the left ventricular wall (0.84 +/- 0.02-vs-0.92 +/- 0.04, P < 0.05 mm). increase in the left ventricular end-diastolic diameter (3.27 +/- 0.15-vs-2.74 +/- 0.05 mm. P < 0.05) and reduction in percent fractional shortening (37 +/- 2-vs-53 +/- 4%, P < 0.05). No differences in these parameters were noted among mice in the uninfected-untreated and uninfected-verapamil-treated groups. Furthermore, right ventricular dilation was more severe in mice from the infected-untreated group as compared with those in the infected- verapamil-treated group (visual grade 1.9 +/- 0.4-vs-1.0 +/- 0.2, P < 0.05). At necropsy, the extent of myocardial injury, as determined histologically, was significantly greater in the infected-untreated mice. These data provide cardiac structural and functional correlates for the previously observed cardioprotective effects of verapamil in chronic chagasic cardiomyopathy. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.