von Willebrand's disease prevents occlusive thrombosis in stenosed and injured porcine coronary arteries.
We studied the role of von Willebrand factor in coronary thrombosis in normal, heterozygous, and homozygous von Willebrand's disease pigs by producing coronary stenosis with a Goldblatt clamp positioned around the left anterior descending coronary artery. Flow velocity was assessed by a 20-MHz Doppler velocity probe distal to the Goldblatt clamp. Myocardial extracellular potassium levels were measured by potassium-sensitive electrodes in myocardium supplied by the left anterior descending artery. Whereas stenosis sufficient to block reactive hyperemia to a 20-second occlusion produced an elevation of myocardial extracellular potassium, it produced neither spontaneous cyclic flow reductions nor permanent cessation of coronary blood flow velocity. Injury of the coronary artery at the stenosis site with spring-loaded forceps produced cyclic flow reductions or permanent cessation of flow in eight of nine phenotypically normal pigs. On the other hand, flow variations occurred in none of the 10 von Willebrand's disease pigs, including four given purified von Willebrand factor at a dose that failed to correct the bleeding time (p less than 0.001, chi 2 test). Permanent cessation of flow was caused by an occlusive platelet-fibrin-red-blood-cell thrombus. Scanning electron micrographs from pigs with cyclic flow variations and from von Willebrand's disease pigs showed injured endothelium covered by adherent platelets, red and white blood cells, and fibrin. These data suggest an important role of native von Willebrand factor in sudden occlusive arterial thrombosis following stenosis and intimal injury.
D000818:Animals; D001783:Blood Flow Velocity; D003250:Constriction; D003251:Constriction, Pathologic / Q000473:pathology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000473:pathology* / Q000517:prevention & control; D003331:Coronary Vessels / Q000473:pathology*; D005337:Fibrin / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000378:metabolism; D010974:Platelet Aggregation; D011188:Potassium / Q000378:metabolism; D013552:Swine; D014842:von Willebrand Diseases / Q000235:genetics / Q000473:pathology*; D014841:von Willebrand Factor / Q000502:physiology*
D014841:von Willebrand Factor; D005337:Fibrin; D011188:Potassium