Tomanek R J, Zimmerman M B, Suvarna P R, Morkin E, Pennock G D, Goldman S
Department of Anatomy, University of Iowa, Iowa City 52242, USA.
J Mol Cell Cardiol. 1998 May;30(5):923-32. doi: 10.1006/jmcc.1998.0671.
In view of the evidence that thyroid hormone administration has angiogenic effects on the hypertrophic myocardium, we tested the hypothesis that the capillary supply in the hypertrophic myocardium surviving infarction would be improved by administration of the thyroid hormone analog, diiodothyroproprionic acid (DITPA). We administered DITPA (MI-DITPA) or saline (MI-saline), s.c., to rats for 10 days following experimental infarction of the left ventricle (LV). Morphometric methods were used to assess capillarity and myocyte cross-sectional area in three regions of the left ventricle: (1) border (next to the scar of infarction); (2) adjacent (next to the border); and (3) remote (interventricular septum). Infarct size ranged from 20-85% of the LV free-wall, and both groups had similar mean infarct size. Capillary length density (LV) was significantly higher in the remote region of the treated group than in the MI-saline rats. LV in the border region, which experienced the most marked increase in cardiocyte cross-sectional area, was not significantly lower than in the other regions, indicating a more marked angiogenic response. In hearts with large infarcts (> or = 40%) LV in the border region was higher in the DITPA group than in the non-treated rats. In the MI-DITPA group, cardiocyte size in the border region was positively correlated with that of the other regions, which contrasts with the negative correlations noted for the MI-saline rats. These data suggest that DITPA therapy (1) may improve maximal perfusion potential of the hypertrophied myocardium surviving a myocardial infarction, and (2) is selectively effective in the border region of hearts with large infarcts.
鉴于有证据表明给予甲状腺激素对肥厚心肌有血管生成作用，我们检验了这样一个假说：给予甲状腺激素类似物二碘甲状腺丙酸（DITPA）可改善梗死存活的肥厚心肌的毛细血管供应。在左心室（LV）实验性梗死之后，我们给大鼠皮下注射DITPA（MI-DITPA）或生理盐水（MI-生理盐水），持续10天。采用形态计量学方法评估左心室三个区域的毛细血管密度和心肌细胞横截面积：（1）边缘区（紧邻梗死瘢痕）；（2）相邻区（紧邻边缘区）；（3）远隔区（室间隔）。梗死面积范围为左心室游离壁的20%-85%，两组的平均梗死面积相似。治疗组远隔区的毛细血管长度密度（LV）显著高于MI-生理盐水组大鼠。边缘区的LV，其心肌细胞横截面积增加最为显著，并不显著低于其他区域，表明血管生成反应更为明显。在梗死面积较大（≥40%）的心脏中，DITPA组边缘区的LV高于未治疗大鼠。在MI-DITPA组中，边缘区心肌细胞大小与其他区域呈正相关，这与MI-生理盐水组大鼠的负相关情况形成对比。这些数据表明，DITPA治疗（1）可能改善心肌梗死后存活的肥厚心肌的最大灌注潜能，（2）对梗死面积较大的心脏边缘区有选择性疗效。
