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 the myocardial punctures of TMR cause a myocardial injury, leading to an angiogenic response mediated by a number of growth factors.


METHODS
Fifty-three rats underwent ligation of the left coronary artery. Group I (n = 25) served as controls, whereas group II (n = 28) underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic zone. Surviving animals in both groups were sacrificed at intervals of 1, 2, 4, and 8 weeks (n = 5 in each subgroup). Immunohistochemistry in the infarct areas was performed for factor VIII to assess vascular density. Immunohistochemistry using specific antibodies was also performed for transforming growth factor-beta, basic-fibroblast growth factor, and vasoendothelial growth factor. Growth factor expression was quantitated by comparing areas of staining (in mm2) with computerized morphometric analysis.


RESULTS
Mortality was similar in both groups (5/25 versus 8/28; not significant). Group II 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 postoperatively (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 TMR group compared with the control group (0.207 versus 0.141 mm2/mm2, p < 0.05; and 0.125 versus 0.099 mm2/ mm2, p < 0.05).


CONCLUSIONS
This model of TMR is associated with a significant angiogenic response, which appears to be mediated by the release of certain angiogenic growth factors such as transforming growth factor-beta and basic-fibroblast growth factor. With the long-term patency of laser-created myocardial channels in clinical TMR increasingly in doubt, its mechanism of myocardial revascularization may be similar to that observed in our model.
Department of Pathology, McGill University, Montreal, Canada.
M P
MP
Pelletier
A
A
Giaid
S
S
Sivaraman
J
J
Dorfman
C M
CM
Li
A
A
Philip
R C
RC
Chiu
D000818:Animals; D004396:Coloring Agents; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000235:genetics; D005169:Factor VIII / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000235:genetics; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D053685:Laser Therapy / Q000379:methods; D008222:Lymphokines / Q000032:analysis* / Q000235:genetics; D008297:Male; D017202:Myocardial Ischemia / Q000601:surgery; D009204:Myocardial Revascularization / Q000379:methods*; D009339:Needles; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014654:Vascular Patency
D004396:Coloring Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D005169:Factor VIII