Precllnical Investigations of Lyophilized Platelet Preparations.

During this period of activity, we published our first comprehensive journal article from results in this project: see Proceedings of the National Academy of Sciences 92:397-401, 1995 (attached). A no-cost extension of the project was approved to extend activities to 31 Aug 96. At the ECU performance site, four trials of hemostatic efficacy of our rehydrated lyophilized platelet preparations were carried out in live pigs according to the Letterman Army Institute animal model of hemorrhagic shock. The results were quite variable and showed the need to adapt this model to emphasize the role of platelets and control other physiologic parameters related to the effects of hypovolemic shock. Attempts in vitro to load rehydrated platelets with calcium ion flux indicator dyes were finally successful, and studies are now underway to measure the responsiveness of these platelet preparations to thrombin and other agonists that rely on Ca2+ for signal transduction. Experiments conducted at UNC showed serotonin uptake and release by rehydrated platelets and surface-related changes in activation. It will be important to continue to define the extent of activation and its control in our rehydrated lyophilized platelet preparations.