Role of von Willebrand factor in mediating platelet-vessel wall interaction at low shear rate; the importance of perfusion conditions.
We have previously observed that von Willebrand factor (vWF) plays an important role in platelet deposition on subendothelium at low values of wall shear rate (200 to 400 seconds-1). In the present study, we have investigated the mechanism responsible for such a defect in platelet deposition at low shear rates in the absence of vWF. Blood from both normal and von Willebrand's disease (vWD) animals was exposed to de-endothelialized aorta from normal pigs for a range of shear rates (200 to 3,000 seconds-1) and exposure times (three to 30 minutes) in a tubular perfusion chamber. Variations in the method of inhibiting coagulation (none, heparin, citrate, hirudin, and EDTA) and of perfusing blood (in vitro v ex vivo) were compared by determining the influence of wall shear rate and vWF on the deposition of 111In-labeled platelets on subendothelium. Whereas platelet deposition was reduced in the absence of vWF for all experimental variations at high shear rates (greater than 850 seconds-1), a defect was observed at low shear rates only when heparinized blood was exposed by means of an ex vivo perfusion system. Maximum sensitivity of the measurement occurs under ex vivo perfusion conditions due to the reduced ability of platelets to deposit in normal blood when recirculated in vitro. Our results indicate that vWF mediates platelet-vessel wall interaction even at low shear rates and that such effect can only be observed in systems where platelet function is minimally affected by the experimental conditions.
Division of Cardiology, Mount Sinai School of Medicine, New York, NY.
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D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001808:Blood Vessels / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D010477:Perfusion; D013314:Stress, Mechanical; D013552:Swine; D014842:von Willebrand Diseases / Q000503:physiopathology; D014841:von Willebrand Factor / Q000502:physiology*
D006629:Hirudins; D014841:von Willebrand Factor; D006493:Heparin