McFalls, Edward O., M.D., Ph.D.

CARDIOLOGY/VASCULAR MEDICINE

Chronic Myocardial Ischemia • I currently have a Merit Review Grant entitled Myocardial adaptations to chronic reductions in blood flow. Using chronically instrumented swine, we have observed distinct metabolic differences between repetitive ischemia and reperfusion that occur in "stunning" and sustained reductions in blood flow that occurs in "hibernation". Enhanced glucose metabolism seems to be an important adaptive process within chronically ischemic hearts but is unlikely to be the primary mechanism of protection. • We are presently looking at changes in isolated mitochondria from chronically ischemic myocardial tissue and have found that apoptosis and necrosis can be prevented by endogenous adaptations. The mitochondria in this acquired “stress-resistant state” demonstrate preserved state 3 respiration following 20 minutes of anoxia/reoxygenation and are characterized by a mild degree of uncoupling under basal conditions and decreased maximal complex III derived superoxide generation. Uncoupling protein 2 expression is also increased in the inner membrane of the mitochondria, and may provide an important mechanism for protection against repetitive oxidant stress. Coronary Artery Revascularization Prophylaxis (CARP) Trial • I am the Principal Proponent of a multicenter Coop Study (CSP #411) involving 18 VA Medical Centers to test whether coronary artery revascularization prior to elective vascular surgery reduces long-term mortality. The period of recruitment is complete and analysis will be done one year following the last randomization.