Hypercholesterolemia impairs myocardial perfusion and permeability: Role of oxidative stress and endogenous scavenging activity

OBJECTIVES We intended to study the effect of hypercholesterolemia (HC) on myocardial perfusion and permeability response to increased cardiac demand. BACKGROUND Hypercholesterolemia is associated with increased incidence of c ardiac events and characterized by impaired coronary vascular function, pos sibly mediated partly through increased pro-oxidative conditions in plasma and tissue. However, it is yet unclear whether HC is also associated with i mpaired myocardial perfusion and vascular permeability responses in vivo. METHODS For 12 weeks pigs were fed a normal, HC or HC diet supplemented dai ly with antioxidants (HC + AO, 100 IU/kg vitamin E and 1 g vitamin C). Myoc ardial perfusion and vascular permeability were measured in vivo using elec tron beam computed tomography before and after cardiac challenge with intra venous adenosine. Plasma and tissue oxidative status was determined ex vivo . RESULTS Plasma cholesterol increased in all cholesterol-fed pigs but was as sociated with increased markers of oxidative stress only in HC pigs. Myocar dial perfusion increased in response to adenosine in normal HC + AO (+37 +/ - 13% and +58 +/- 22%, respectively, p < 0.05 vs. baseline) but not in HC, whereas vascular permeability index increased only in HC pigs (+ 92 +/- 25% , p = 0.002). In HC animals, tissue endogenous oxygen radical scavengers an d antioxidant vitamins were depleted and LDL oxidizability enhanced, but bo th were normalized in HC + AO pigs. Myocardial perfusion response was direc tly, and permeability inversely, associated with plasma and tissue vitamin concentrations. CONCLUSIONS This study demonstrates that experimental HC is associated with blunted myocardial perfusion and increased vascular permeability responses in vivo to increased cardiac demand, which may be partly mediated by a shi ft in oxidative status. (C) 2001 by the American College of Cardiology.