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8TH INTERNATIONAL SYMPOSIUM ON RESISTANCE ARTERIES
New Developments in Resistance Artery Research: From Molecular Biology to Bedside

Marriage of resistance and conduit arteries breeds critical limb ischemia

Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, United Kingdom

Submitted 30 July 2004 ; accepted in final form 13 September 2004

Atherosclerosis in a major leg artery leads to impaired blood supply, which normally progresses to critical limb ischemia. Atherosclerosis produces substantial alterations of structure and endothelial function in the large conduit arteries. Pressure unloading and ischemia in the distal vasculature bring about alterations in microvascular function. Resistance arteries undergo significant wall thinning and changes in their contractile regulation. Optimization of large artery dimensions by the small arteries through flow-mediated vasodilation is impaired. Angiogenesis is stimulated, which can result in the formation of major collateral feeder vessels in addition to small nutritive blood vessels. However, angiogenesis can also contribute to instability of atherosclerotic plaques, which ultimately leads to further deterioration in blood supply. Surgical bypass grafting to restore blood supply to the distal leg generates a sudden increase of pressure in the weakened resistance vasculature, leading to uncontrolled changes in capillary hydrostatic pressure, extravasation of fluid, and tissue edema. This review aims to highlight the importance of the resistance vasculature in critical limb ischemia and the interdependence of pathophysiological changes in the large conduit and small resistance arteries. The major unresolved question is why the physiological mechanisms that regulate vascular structure and function ultimately break down, leading to circulatory failure within the distal limb.

microvessels; nitric oxide synthase; cyclooxygenase; inflammation; vascular diseases

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				S. A Arain and C. J White Endovascular therapy for critical limb ischemia Vascular Medicine, August 1, 2008; 13(3): 267 - 279. [Abstract] [PDF]