ANGIOGENESIS AND GROWTH-FACTOR EXPRESSION IN A MODEL OF TRANSMYOCARDIAL REVASCULARIZATION

Background, The mechanism by which transmyocardial revascularization ( TMR) exerts a beneficial effect remains unknown. We hypothesize that t he myocardial punctures of TMR cause a myocardial injury, leading to a n angiogenic response mediated by a number of growth factors. Methods. Fifty-three rats underwent ligation of the left coronary artery. Grou p I (n = 25) served as controls, whereas group II (n = 28) underwent c oncomitant TMR by the creation. of six transmural channels with a 25-g auge needle in the ischemic zone. Surviving animals in both groups wer e sacrificed at intervals of 1, 2, 4, and 8 weeks (n = 5 in each subgr oup). Immunohistochemistry in the infarct areas was performed for fact or VIII to assess vascular density. Immunohistochemistry using specifi c antibodies was also performed for transforming growth factor-beta, b asic-fibroblast growth factor, and vasoendothelial growth factor. Grow th factor expression was quantitated by comparing areas of staining (i n mm(2)) with computerized morphometric analysis. Results. Mortality w as similar in both groups (5/25 versus 8/28; not significant). Group I I had significantly greater vascular density than group I (5.65 versus 4.06 vessels/high-power field; p < 0.001), with a peak at 1 week post operatively (9.12 versus 5.56 vessels/high-power field; p < 0.0001) in both groups. Overall, levels of both transforming growth factor-beta and basic-fibroblast growth factor were significantly higher in the TM R group compared with the control group (0.207 versus 0.141 mm(2)/mm(2 ), p < 0.05; and 0.125 versus 0.099 mm(2)/ mm(2), p < 0.05). Conclusio ns. This model of TMR is associated with a significant angiogenic resp onse, which appears to be mediated by the release of certain angiogeni c growth factors such as transforming growth factor-beta and basic-fib roblast growth factor. With the long-term patency of laser-created myo cardial channels in clinical TMR increasingly in doubt, its mechanism of myocardial revascularization may be similar to that observed in our model. (Ann Thorac Surg 1998;66:12-8) (C) 1998 by The Society of Thor acic Surgeons.