Project: Research project

Project Details


The two main focuses of this competitive renewal application are
1) to continue our intensive experimental studies on isovolemic
hemodilution and 2) to investigate the effects of fluid replacement
with crystalloids (Ringer's lactate-RL) and compare them with the
effects of colloids (low molecular weight dextran-LMD) in a model
of focal cerebral ischemia. Three main projects are proposed for
the 3 year period of the application.

The first project will compare the effects of isovolemic
hemodilution with crystalloid and colloid. 75 dogs ((60 with
internal carotid (ICA) and middle cerebral artery (MCA) occlusion
for 6 hours, equally divided in 3 groups: hemodiluted with RL, LMD
or not hemodiluted; 15 sham operated, equally divided in 3 groups
as controls)) will be studied during the first 2 years.
Hemodynamic, rheologic and hematologic parameters and neurological
grades will be studied sequentially after arterial occlusion. The
volume of brain infarct as determined by fluorescein staining and
histopathology will then be compared.

The second project to be undertaken during the first 2 years is
divided in 2 parts. In the first part we will study the changes
in regional cerebral blood flow (rCBF) and tissue oxygen
availability (O2a) as the Hct is lowered by 5% decrements from 40
to 25% by stepwise hemodilution in rabbits with occlusion of the
ICA and MCA. 30 rabbits will have arterial occlusion (20
hemodiluted and 10 controls) and 10 will be sham operated (5
hemodiluted and 5 sham controls). For the second part four groups
of 15 rabbits each will be used either as controls (Hct 40%) or as
hemodiluted groups (Hct 35%, 30% and 25% respectively). Sequential
changes on rCBF and O2a and volume of brain infarction in the four
groups will be compared.

The last project will compare the effects of hemodilution at 1
hour. 6 hours and 24 hours after permanent occlusion of the ICA
and MCA in dogs (15 dogs in each group and 15 non-hemodiluted
controls). Since there is no experience with permanent occlusion
in this model, we will perform, before commencing this project, a
feasibility study with 6 dogs to ascertain the probability of
survival and the severity of the resulting infarct.
Effective start/end date12/31/893/31/91


  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke


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