Angiogenic growth factor and revascularization of the ischemic limb: evaluation in a rabbit model.
We have previously shown that administration of endothelial cell growth factor (ECGF) significantly accelerates revascularization in the ischemic rabbit hindlimb model. Nevertheless, much remains to be learned as to the effectiveness and limitations of this approach. The present study was designed, therefore, to determine whether a dose-response relationship could be demonstrated for this agent, whether it was effective if systemically administered, and finally, whether it affected vascularization in a nonischemic limb. Our established unilateral ischemic rabbit hindlimb model and ECGF administration protocol were used to examine these questions. Three groups of animals were studied to determine a dose-response relationship of ECGF in the ischemic limb. Revascularization was assessed by measurement of calf blood left to right (L/R) pressure ratio before (Day 0) and after ECGF injections (Days 1, 10, and 20) and quantitative vascularization was assessed by angiography at Day 20 when the study was terminated. The results of the dose-response study were [formula: see text] Two other groups of animals were also studied. In Group 4, intramuscular ECGF was injected in the left front limb remote from the ischemic hindlimb and in Group 5 it was injected into the left hindlimb of a normal animal. In neither group was any significant effect on vascularization evident. Thus, our data suggest that the relationship of ECGF and revascularization of the ischemic limb is dose dependent and is demonstrable only when it is administered directly into the limb in the presence of ischemia.