The effects of ischemia and hypercholesterolemia on the function and morphological adaptation of the rabbit hindlimb were assessed.Methods
In rabbits on normal or cholesterol diet, experiments were performed on days 0–28 following bilateral femoral artery ligation. Calf blood pressure (CBP), exercise tolerance, flow reserve, agonist vasodilatation, angiography and capillary density were examined and modeled.Results
CBP decreased markedly post-ligation and returned to 41 and 68% of baseline by days 7 and 28. Exercise tolerance was attenuated 40% and flow reserve 50–60% on day 7, with recovery by day 28. Ligation caused decreases in 5-hydroxytryptamine-induced dilatation, while adenosine and acetylcholine responses were unaffected. Hypercholesterolemia attenuated acetylcholine-elicited dilatation. There was marked loss of adenosine dilatation on days 7–14 in the ligation plus hypercholesterolemia group. Ligation caused a doubling in the number of medium-sized collateral arteries. Hypercholesterolemia, either alone or combined with ligation, greatly augmented small vessel density. Capillary density was unaltered by any treatment.Conclusions
The rabbit hindlimb shows a remarkable ability to recover its muscle function through vascular adaptation and remodeling 4 weeks following ligation, with or without hypercholesterolemia. Exercise tolerance, flow reserve and vascular reactivity were mainly restored 28 days post-ligation.