Laser Doppler imaging of reactive hyperemia exposes blood flow deficits in a rat model of experimental limb ischemia.
The primary pathophysiology of peripheral artery occlusive disease is associated with impaired perfusion to the lower extremities. The lack of effective pharmacologic agents to treat this disease emphasizes the need for well-characterized animal models that can be used to evaluate the efficacy of emerging therapies. A major limitation with the current animal models of peripheral artery occlusive disease is that the variety of surgical methods employed to reduce peripheral blood flow produce differences in the severity and time course of the resting and reserve blood flow deficits. Furthermore, the methods used to evaluate the restoration of peripheral flow are often not suitable for serial measurements. This study used laser Doppler imaging to serially evaluate resting blood flow and the development of a functional collateral circulation after the induction of hind limb ischemia in the rat. Reserve blood flow was assessed by measuring hyperemic blood flow in the hind paw after temporary arterial occlusion. The magnitude of the hyperemic response was found to be dependent upon both the duration of arterial occlusion and the measurement time after release of the occluder. After ligation of the common iliac artery, but at a time when resting blood flow was reestablished, hyperemic tests unmasked a sustained deficit in reserve blood flow capacity that persisted for at least 14 days. Therefore, the use of a noninvasive vascular occluder and laser Doppler imaging represents a sensitive and consistent technique to measure peripheral blood flow status to assess the development of functional collateral vessels. These findings will enhance the ability to effectively study pharmacologic therapies aimed at promoting the growth and development of collateral vessels.
Department of Molecular Endocrinology, Merck Research Laboratories, West Point, PA 19454, USA.
Halea A
HA
Corcoran
Brad E
BE
Smith
Parker
P
Mathers
Dan
D
Pisacreta
James C
JC
Hershey
D000818:Animals; D003097:Collateral Circulation; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply*; D006940:Hyperemia / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow