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The Journal of Nutrition Vol. 127 No. 7 July 1997, pp. 1320-1327
Copyright ©1997 by the American Society for Nutritional Sciences

Von Willebrand Factor Restores Impaired Platelet Thrombogenesis in Copper-Deficient Rats

Manuscript received 19 December 1996. Initial reviews completed 14 January 1997. Revision accepted 25 March 1997.

David Lominadze, Jack T. Saari*, Frederick N. Miller, James L. Catalfamodagger , and Dale A. Schuschke

Center for Applied Microcirculatory Research, University of Louisville, Louisville, KY 40292; * U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202; and dagger  Diagnostic Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY 15851

Dietary copper restriction reduces microvascular thrombogenesis. We have now examined the roles of shear forces and von Willebrand factor (vWF ) in in vivo thrombus formation in the cremaster microcirculation of copper-deficient rats. Male weanling Sprague-Dawley rats were fed purified diets that were either copper-adequate (6.3 mg Cu/kg) or copper-deficient (0.3 mg Cu/kg) for 4 wk. Intravascular fluorescein isothiocyanate tagged to bovine serum albumin was activated with 450-490 nm light to induce thrombus formation in microvessels. Thrombus initiation time was significantly prolonged in copper-deficient rats; after thrombus appearance, however, vessel occlusion was significantly accelerated. The greater shear rates of arterioles compared with venules significantly increased the thrombus initiation time in both groups. However, vessel occlusion time and thrombus growth time were independent of shear rate. Intravascular vWF (0.2 U/100 g body wt) decreased thrombus initiation time in the CuD group without affecting thrombus growth time. The data suggest that decreased thrombogenesis in copper-deficient rats is not a result of altered rheological factors or arteriolar-venular differences, but appears to result from decreased platelet-to-endothelial cell adhesion.

Key words: rats, microvessels, shear rate, thrombogenesis, von Willebrand factor.




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