A THYROID-HORMONE ANALOG STIMULATES ANGIOGENESIS IN THE POST-INFARCTED RAT-HEART

In view of the evidence that thyroid hormone administration has angiog enic effects on the hypertrophic myocardium, we tested the hypothesis that the capillary supply in the hypertrophic myocardium surviving inf arction would be improved by administration of the thyroid hormone ana log, diiodothyroproprionic acid (DITPA). We administered DITPA (MI-DIT PA) or saline (MI-saline), s.c., to rats for 10 days following experim ental 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 infarct ion); (2) adjacent (next to the border); and (3) remote (interventricu lar septum). Infarct size ranged from 20-85% of the LV Gee-wall, and b oth groups had similar mean infarct size. Capillary length density (L- v) was significantly higher in the remote region of the treated group than in the MI-saline rats. L-v in the border region, which experience d the most marked increase in cardiocyte cross-sectional area, was not significantly lower than in the other regions, indicating a more mark ed angiogenic response. In hearts with large infarcts (greater than or equal to 40%) L-v in the border region was higher in the DITPA group than in the non-treated rats. In the MI-DITPA group, cardiocyte size i n the border region was positively correlated with that of the other r egions, which contrasts with the negative correlations noted for the M I-saline rats. These data suggest that DITPA therapy (1) may improve m aximal perfusion potential of the hypertrophied myocardium surviving a myocardial infarction, and (2) is selectively effective in the border region of hearts with large infarcts. (C) 1998 Academic Press Limited .