Coronary restenosis: prospects for solution and new perspectives from a porcine model.
Coronary restenosis, a major unresolved problem for percutaneous coronary revascularization procedures, has thus far been resistant to all therapeutic strategies. In part, ineffective treatment or prevention of coronary restenosis may be due to reliance on a conceptualization of the restenosis process that incompletely reflects the pathophysiologic factors associated with neointimal formation after arterial injury. In a porcine coronary restenosis model, three stages of neointimal growth after arterial injury have been identified: an early thrombotic stage, with platelets, fibrin, and erythrocytes; a cellular recruitment stage, with endothelialization and an infiltration by lymphocytes and monocytes; and a proliferative stage, in which smooth muscle cells migrate into and proliferate within the fibrin-rich degenerating thrombus. Evaluation of basic mechanisms responsible for neointimal formation has been possible with this model. In particular, a direct relationship exists between the depth of arterial injury and subsequent neointimal thickness. This relationship can be used for investigating the efficacy of new therapies. Treatment strategies for restenosis should be directed toward interference with the cellular or humoral events that lead to neointimal formation, with the specific goal of decreasing the neointimal volume. These strategies may include delivery of drugs to the site of arterial injury to limit the amount of early mural thrombus or decreasing subsequent cellular recruitment and proliferation as well as synthesis of extracellular matrix.
Schwartz
R S
RS
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905.
Edwards
W D
WD
Huber
K C
KC
Antoniades
L C
LC
Bailey
K R
KR
Camrud
A R
AR
Jorgenson
M A
MA
Holmes
D R
DR
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000503:physiopathology; D012008:Recurrence; D013552:Swine; D017539:Tunica Intima / Q000503:physiopathology
D000925:Anticoagulants