PLATELET INTERACTION AND EFFICACY STUDIES OF LEH

Project: Research project

Project Details

Description

This primary focus of this project is to evaluate the pathophysiological
mechanisms of thrombocytopenia induced by an infusion of liposome
encapsulated hemoglobin (LEH) and to quantitate changes in oxygen uptake
and oxygen delivery of LEH over time after administration in small animal
models. We plan to investigate this LEH-induced thrombocytopenia using
both in vitro and in vivo radiolabeled platelet studies in rat and rabbit
models. The proposed in vivo studies will use non-invasive imaging of
platelets labeled with indium- 111 to assess the effect of complement
depletion, inhibition of arachidonic acid metabolism, and in vivo platelet
aggregation inhibitors on platelet biodistribution following
administration of LEH. Formulations of LEH less likely to cause
thrombocytopenia will be investigated. A second aim of this project is the
investigation of LEH oxygen uptake and tissue delivery. Specifically,
several new techniques based on the short lived positron emitting
radioisotope of oxygen, oxygen-15 (15-O) (t 1/2 = 2.O2 minutes), will be
used to investigate the ability of LEH to load oxygen from the lungs and
deliver oxygen to the tissues in small animal models (rats and rabbits).
Changes in oxygen carrying capacity and oxygen tissue extraction will be
assessed over a period of time post-infusion and correlated with the
clearance time course. Formulations of LEH that may potentially have
prolonged circulation times, a longer effective oxygen carrying capacity,
and efficient oxygen delivery to the tissues will be assessed using these
new techniques. These studies will provide important information necessary
for the development and continual improvement in the formulation of LEH as
a safe and efficacious blood substitute. These studies will provide a
better understanding of both the mechanisms of toxicity and the factors
which govern the delivery of oxygen to the tissues. The tracer techniques
described in this proposal will provide new tools that could generally be
applied to the study of blood substitutes.
StatusFinished
Effective start/end date8/1/947/31/98

Funding

  • National Institutes of Health
  • National Institutes of Health: $197,759.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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