Thrombosis triggered by severe arterial lesions is inhibited by oral administration of a glycoprotein IIb/IIIa antagonist

Platelet aggregation and thrombosis play an important role in the onset of acute coronary events. Regardless of the stimulus for activation, platelet thrombus formation is ultimately regulated through the IIb/IIIa receptor complex. The effects of oral administration of xemilofiban, a non-peptide mimetic of the RGDF sequence of the IIb/IIIa receptor complex, on thrombus formation were evaluated in a canine model. Xemilofiban significantly reduced platelet deposition on severely damaged arterial wall. Platelet deposition was reduced at both low (13 ± 1 from 56 ± 18 × 10⁶ platelets cm⁻²; P  < 0.05) and high (23 ± 2 from 111 ± 21 × 10⁶ platelets cm⁻²; P  < 0.01) shear rates. Platelet deposition was reduced to a monolayer as seen by electron microscopy (platelet–vessel wall interaction). Therefore, the availability of an orally active IIb/IIIa antagonist for chronic use may have significant value in preventing thrombus formation in those clinical situations associated with severe arterial injury, such as atherosclerotic plaque disruption.     

Effect of meal volume on gastric emptying

Abstract While the volume of a liquid meal has been identified as the principal accelerator of gastric emptying of liquids, the relationship between meal volume and gastric emptying of solids has been controversial. With solid foods, the need to reduce solid foods into small particles (trituration) before passage might obscure the effect of meal volume on solid propulsion. To distinguish trituration from driving force as the rate-limiting factor for emptying, 75 (1.6 mm) nylon spheres were fed along with different amounts of steak meals (150, 300 and 600 g), or alternatively, 50, 100 or 200 (1.6 mm) nylon spheres were fed to six dogs with 300 g steak meals. To examine the effect of meal volume on gastric emptying, we studied the effect of different meal volumes on the speed of gastric emptying of liquids (150, 300, 600 and 1200 ml of phosphate buffer) and solids (150, 300 and 600 g of cooked beef steak) in five dogs with duodenal fistulas. Intestinal inhibition was eliminated by diverting all chyme through the fistulas. In the absence of intestinal feedback, we found that gastric emptying of steak and spheres were different in that steak emptying was independent of meal volume (g min^-1 was constant across 150–600 g) while sphere emptying was affected by the number of spheres in the stomach and that liquid emptying was dependent on the meal volume (ml min^-1 increased across 150–1200 ml). Thus, meal volume accelerated gastric emptying provided the process is not rate-limited by trituration.