This report describes a rapid and efficient method of assessing the survival of human platelets in a rabbit model using flow cytometry. This technique will enable the monitoring in rabbits of human platelets prepared by various preservation protocols.
It is possible to freeze platelets and retain in vivo efficacy if the cryopreservative DMSO is included in the preparation. In vitro responses were greatly reduced by all of the storage protocols, but it may not be necessary to retain 100 percent in vitro function to have a platelet substitute or storage product that functions satisfactorily in vivo.
This is the first report describing a kidney injury model developed to assess the efficacy of fresh and activated human platelets in reducing blood loss in thrombocytopenic rabbits. This model could monitor the efficacy of human platelets prepared by various preservation protocols in suppressing bleeding in rabbits.
In an animal model of nonlethal endotoxemia, infusion of alpha alpha Hb significantly increases mortality. Our data suggest that mortality may be due to the acute increased cardiopulmonary toxicity of alpha alpha Hb in animals with underlying endotoxemia.
The present study compared the activities of recombinant tissue-type plasminogen activator (t-PA) and a plasminogen activator inhibitor-1 (PAI-1)-resistant variant t-PA (Kt-PA, KHRR 296–299 AAAA) in preventing renal fibrin deposition in rabbits with elevated PAI-1 activity. In this model, all rabbits were infused with endotoxin (10 micrograms/kg), followed by initiation of thrombin (130 U/kg) 4 hours later, when plasma PAI-1 activity was greater than 200 arbitrary units (AU)/mL (baseline, < 3 AU/mL). Thirty minutes after completion of the 1-hour thrombin infusion, rabbits were killed and the kidneys fixed and stained for identification of fibrin deposition. Rabbits received one of the following treatments initiated 30 minutes before thrombin and continued during the 1-hour thrombin infusion: (1) saline (n = 7); (2) low-dose t-PA (17 micrograms/kg, n = 4); (3) higher-dose t-PA (170 micrograms/kg, n = 4); or (4) low-dose Kt-PA (17 micrograms/kg, n = 6). Fibrin deposition occurred in 86% and 100% of the rabbits receiving saline or low-dose t-PA, respectively. Fibrin deposition did not occur in any of the rabbits receiving low-dose Kt-PA or higher-dose t-PA. Low-dose Kt-PA and higher dose t-PA also caused a reduction in fibrin deposition when infused after thrombin administration had been completed. The data provide in vivo evidence that Kt-PA is more effective than t-PA in preventing fibrin deposition in an animal model that combines thrombogenic stimulation with increased PAI-1 activity.
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