Structural and functional limitations of the collateral circulation in peripheral artery disease

Abstract

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis where, typically, atherosclerotic plaque formation in arteries to the legs results in a decrease in limb blood flow. Symptomatically, this manifests as pain in the lower limbs upon exertion and/or at rest depending on the severity of the occlusion. Symptomatic PAD is prevalent in the elderly population and puts patients at a significantly higher risk of myocardial infarction and stroke. Those with asymptomatic PAD (up to 75% of PAD cases), which may be as prevalent as 10–15% of the adult population, are at higher risk for cardiovascular morbidity and mortality (for reviews see Hackam et al. 2005; Chi & Jaff, 2008). PAD is one of many current, urgent health problems and given risk factors that include age, diabetes mellitus, smoking, hypertension and hyperlipidemia, a higher prevalence of PAD is predicted for the future. Interventions currently employed to ease the symptoms of PAD include surgical and pharmacological options as well as a recommendation for lifestyle changes, in terms of both diet and activity. The physiological adaptations to PAD are to remodel the collateral blood vessel circuit being used in lieu of the occluded arteries by increasing both the diameter and number of vessels within the circuit. These adaptations can help restore resting blood flow levels. A paper in this issue of The Journal of Physiology by Taylor et al. (2008) shows that the collateral circuitry is not an effective substitute to accommodate the higher flows necessary during activity. Taylor et al. demonstrate that both physiological and anatomical constraints of the collateral circulation limit limb blood flow during femoral artery occlusion and highlight the potential importance of regular physical activity at overcoming both obstacles. Their first important finding was that the collateral circuit is influenced by sympathetic vasoconstriction (via α-adrenergic and neuropeptide Y1 membrane receptors) during exercise in both acute and chronic occluded states, and chronically in both sedentary and trained animals; therefore the influence of sympathetic vasoconstriction is maintained during vascular remodelling. They demonstrate further that the conductance of the collateral circuit of exercise trained animals was significantly greater than in sedentary animals. Therefore, increased sympathetic nervous activity during exercise promotes collateral vessel vasoconstriction which can limit limb blood flow, yet training can ameliorate the impact of this limitation. Their second important finding was that the low conductance of the collateral circuitry during exercise may be limited by the capacity of the circuit itself. Taylor et al. (2008) surmised that the remodelling process may render the vessels less reactive or less distensible. They showed that isolated blood vessels with chronic, restricted blood flow display a different flow-pressure relationship having a greater increase in diameter for a given perfusion pressure when compared to non-occluded controls. This structural adaptation would allow for increased blood flows in the face of lower perfusion pressures but ultimately indicates that the collateral vessels are, indeed, different in their responsiveness. Given that the collateral blood vessels are smaller in diameter than the conduit arteries they are trying to replace, even with the remodelling, they will offer more resistance and decrease the perfusion pressure of the vasculature below the collaterals. Therefore, blood flow to the lower limbs will ultimately be limited by the overall capacity of the collateral circuit. Increasing the capacity of the circuit may be an important element in the treatment of PAD, thus underscoring the importance of understanding the processes of arteriogenesis. This study also endorses the importance of regular physical activity. In observing that the conductance of the collateral circuit of exercise trained animals is significantly greater than in sedentary animals during exercise, they show that regular physical activity can overcome, in part, both the physiological (sympathetic vasoconstriction) and structural limitations (remodelling modifications) of the collateral circulation. Therefore, any prescription for the symptoms for PAD should include regular physical activity for those that are able.