Content area
Full text
Arterial occlusive diseases are a major cause of morbidity and death in the United States. The enlargement of pre-existing vessels, which bypass the site of arterial occlusion, provide a natural way for the body to compensate for such obstructions. Individuals differ in their capacity to develop collateral vessels. In recent years much attention has been focused upon therapy to promote collateral development, primarily using individual growth factors. Such studies have had mixed results. Persistent controversies exist regarding the initiating stimuli, the processes involved in enlargement, the specific vessels that should be targeted, and the most appropriate terminology. Consequently, it is now recognized that more research is needed to extend our knowledge of the complex process of collateral growth. This basic science review addresses five questions essential in understanding current problems in collateral growth research and the development of therapeutic interventions.
Introduction
In 1953, C. J. Longland delivered the Arris and Gale Lecture at the Royal College of Surgeons of England. In his lecture entitled, "The Collateral Circulation of the Limb," he considered mechanisms or stimuli that promote the growth of preexisting vessels that offer an alternative path for blood flow after occlusion of a main artery. In his conclusion, Longland emphasized the importance of collateral circulations by stating that "... they will remain the sheet anchor in the management of obliterative arterial disease until the obliterative processes themselves can be controlled."
Fifty years later, we have yet to learn to control the obliterative processes. Peripheral arterial disease (PAD) of the occlusive variety is a common problem, occurring in an estimated 8 to 12 million patients in the United States.1 The incidence of PAD increases with age, so that more than 10% of patients age 65 and older and more than 20% of patients age 80 and older are affected by the disease.2 With the U.S. elderly population increasing,3 the number of patients with PAD will continue to increase. The majority of patients with PAD are asymptomatic,4 but an estimated 1 million patients in the United States become symptomatic with intermittent claudication each year.5 Of these patients with intermittent claudication, approximately 15% to 20% will experience progression to critical leg ischemia.5 More than 100,000 operations are performed each year on patients with lower extremity...