Histologic evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser revascularization

Objectives. To determine whether addition of basic fibroblast growth factor (bFGF), an angiogenic growth factor, enhances the angiogenic effects of tr ansmyocardial laser revascularization (TMR). Background. TMR is an investigational therapy for treating patients with me dically refractory angina not amenable to traditional therapies. Histologic and blood flow studies in animals have suggested that TMR enhances angioge nesis above that normally seen in ischemic myocardium. We tested the hypoth esis that bFGF administered into TMR channels further enhance the angiogeni c effects of TMR. Methods. Chronic ischemia was created in 3 groups of dogs using an ameroid constrictor on the proximal LAD. In the bFGF group (n = 5) non-transmyocard ial channels were created in the LAD territory and bFGF, (100 ng/ml) dissol ved in pluronic gel was injected into the each channel. In the TMR group (n = 7), transmyocardial channels were created without bFGF A control group ( n = 7) had ischemia without TMR of bFGF 5-bromo-2'-deoxyuridine (BrdU) was administered to mark proliferating cells. After 8 weeks survival, colored m icrospheres were injected to assess the regional myocardial blood flow. Results. TMR and TMR+bFGF increased total vascular density by similar to 40 % over that observed in the control group. However, the number of large ve ssels (internal diameter greater than or equal to 50 mu m) was doubled by t he addition of bFGF, and this correlated with a 50 % increase in the densit y of proliferating vascular cells and a tripling of the total estimated vas cular cross sectional area. Blood flow to the LAD territory was increased b y TMR compared to controls, with no further benefit observed in the bFGF gr oup. Conclusions. On a histologic basis, basic fibroblast growth factor further enhances angiogenesis following TMR in ischemic myocardium mainly by increa sing the size but not the total number of vessels.