Abstract 1015: Intracoronary Administration of AdvFGF-5 Improves Coronary Flow Reserve and Myocardial Function in Swine with Ischemic Cardiomyopathy and Developing Coronary Collaterals
Background: We previously demonstrated that overexpression of AdvFGF-5 in swine with stable coronary collaterals and hibernating myocardium failed to alter myocardial perfusuion which is consistent with the negative findings in a number of clinical trials in patients with stable chronic coronary artery disease. We hypothesized that this was related to the absence of acute ischemia and could be overcome by administering AdvFGF-5 prior to the development of collateral-dependent myocardium.
Methods: Swine were chronically instrumented with 1.5 mm stenoses on the LAD and LCX arteries. Studies began 1 month after instrumentation at which time the coronary arteries were stenotic, LAD wall thickening was reduced and there were no angiographic collaterals. Using a percutaneous brachial technique, we administered a total of 2 x1012 vp of AdvFGF-5 (n = 9) or the inactive reporter AdvEGFP (n = 6) into the 3 major coronary arteries after i.c. histamine. Physiological studies to assess function and flow (microspheres) at rest and adenosine vasodilation were performed 4 weeks later.
Results: Measurements of Ejection Fraction, LAD wall thickening and relative adenosine flow reserve are summarized below (Table⇓). There were no differences in baseline flow, function or systemic hemodynamics between the two groups. In animals treated with AdvEGFP, there was a progressive reduction in global function and coronary flow reserve. In contrast, relative flow during adenosine vasodilation, Ejection Fraction and LAD wall-thickening increased after AdvFGF-5.
Conclusion: In swine without pre-existing collaterals, there is a prominent effect of AdvFGF-5 on function and angiogenesis. This suggests that a favorable response to angiogenic interventions is critically dependent upon the upregulation of endogenous angiogenic mechanisms arising from intermittent myocardial ischemia and unlikely to be beneficial when coronary collaterals have reached a stable level.