title: Modelling coronary thrombosis from nonanticoagulated human blood in vitro.
abstract: The prevalence of ruptured atheromatous plaques underlying the adherent thrombus in the infarct-related coronary arteries, is well documented. In the thrombotic process associated with plaque rupture, hemodynamic forces and the interaction of platelets with exposed collagen fibers play the decisive roles. The shear-induced hemostasis from a nonanticoagulated human blood sample, perfused through polyethylene tubing, was used to simulate rheological changes in the coronary circulation due to plaque disruption. When the hemodynamic conditions of a plaque fissure were mimicked, the sequence of events corresponded to that in vivo: hemostasis (i.e., platelet plug formation in the wall) resulted in the formation of an occlusive thrombus in the lumen of the tubing. Further, the thrombus growth on a collagen fiber, mounted in the lumen of polyethylene tubing through which nonanticoagulated human blood was perfused, was used to mimick the exposure of thrombogenic elements during deep vessel wall injury and the formation of thrombus superimposed on plaque disruption. Morphology of both types of thrombi revealed large numbers of neutrophils and monocytes associated with the platelet mass. The mechanisms of thrombotic reactions were characterized by antagonists and monoclonal antibodies against the platelet activation pathways. Generation of thrombin at an early stage was shown to be the key event and determinant of the final outcome of both thrombotic reactions. It is suggested that the simultaneous measurements of shear-induced hemostasis, clotting, and platelet-collagen interaction from nonanticoagulated human blood provide close experimental approximations to the pathological process of acute coronary syndromes, namely thrombus formation at the site of a disrupted atherosclerotic plaque.
authors.affiliation: Department of Hematology, St. Bartholomew's Hospital, School of Medicine, London, England.
authors.forename: P
authors.initials: P
authors.lastname: Görög
authors.forename: I B
authors.initials: IB
authors.lastname: Kovacs
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D003094:Collagen / Q000097:blood; D003327:Coronary Disease / Q000097:blood*; D003328:Coronary Thrombosis / Q000097:blood* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006487:Hemostasis; D006801:Humans; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008954:Models, Biological; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000032:analysis; D010587:Phagocytosis / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects; D013314:Stress, Mechanical
chemical_list: D003094:Collagen