Exercise Training Improves Peripheral Vascular Function Following Chronic Femoral Artery Occlusion in the Ossabaw Swine Model of Cardiometabolic Risk

Abstract

PURPOSE: Peripheral arterial disease (PAD) is a major cause of morbidity and mortality in the developed world. Diabetes is a strong risk factor for PAD; thus, incidence of PAD can only be expected to rise as the prevalence of diabetes increases. The treatment of choice for PAD is exercise training. Training is well-known to increase collateral-dependent peripheral blood flow in healthy animals, mainly rodents. However, it is unclear whether training induces the same changes in collateral structure and/or function in the setting of the metabolic syndrome. Thus, we investigated peripheral vascular function in Ossabaw swine. Results from this unique large animal model of cardiometabolic risk may be closely relevant to human disease. METHODS: Swine were divided into 3 groups: sedentary control (C, N=6), sedentary high fat/cholesterol fed (H, N=4), and exercise trained H (HX, N=6). H and HX pigs were fed a high fat/cholesterol diet (46% kcal from fat; 2% cholesterol w:w) for 50 wk. Hydrogenated soybean oil (containing 56% trans fatty acids) served as the fat source. H and HX pigs were obese, hyperlipidemic, hypertensive, and insulin resistant, all characteristics of the metabolic syndrome. HX pigs trained on a motorized treadmill 4 d/wk for 7 wk. Pigs wore a wireless heart rate monitor for continuous assessment of exercise intensity. After a 10-min warmup, treadmill speed was increased until heart rate reached ∼65-75% of max. Pigs then exercised for 30 min, followed by a 5-min cool down. After 4 wk of training, the right femoral artery was occluded under general anesthesia using surgical suture. After recovery, pigs continued training for a further 3 wk. Pigs were then anesthetized for measurement of mean saphenous artery pressure (SAP). RESULTS: SAP did not differ between groups in the left (non-occluded) limb. Left SAP fell ∼50% in all groups in response to acute occlusion of the left femoral artery and did not significantly recover by 10 min post-occlusion. In the right (chronically occluded) limb, SAP was significantly higher in HX than in C pigs (71 ± 5 vs 49 ± 5 mm Hg; p=0.013). Recovery of SAP after 4 wk of femoral occlusion was complete in the HX group (113 ± 14% of pre-occlusion left SAP), and was greater than that in the H group (48 ± 23%; p=0.017 vs HX) or the C group (75 ± 8%, p=NS vs HX). Typical "corkscrew" collaterals were angiographically visible in the right thigh, suggesting that structural remodeling occurred in response to the chronic femoral occlusion. CONCLUSIONS: Exercise training significantly improves peripheral vascular function in obese Ossabaw swine, a novel and useful large animal model for the study of the effects of exercise on PAD. Support: HL062552, RR013223 (MS).