An animal model for sickle cell vasoocclusion using rats and dogs will be developed to study the factors responsible for initiation and propagation of the vasoocclusive event. We will explore the roles of localized anoxia, hypotension, and tissue damage in the initiation of vasoocclusion, and the roles of non-deformable versus deformable but polymerizable sickle cells in the propagation of vasoocclusion. A Percoll-Stractan continuous density gradient system developed in this laboratory will be used to separate cells from patients with sickle cell anemia into different density classes which have been previously shown to contain deformable but polymerizable cells or non-deformable and polymerizable cells. The relative efficiency of unseparated saline-washed sickle cells, density fractionated sickle cells, and glutaraldehyde fixed human and rat cells at initiating and sustaining a vasoocclusive event will be compared. Vasoocclusion in the rat leg will be studied by injecting washed sickle cells into the femoral artery. Other animal models will be developed to study bone and bone marrow infarction and acute chest syndrome. The manifestations of infarct by sickle cells will be examined using technetium-99m (99mTc) imaging to delineate the area and extent of cell trapping; H-1 and Na-23 magnetic resonance imaging (MRI) to determine the area and time course of tissue damage; F-19 MRI to determine tissue oxygenation and tissue perfusion (by observation of F-19 washout time); and P-31 and H-1 high resolution NMR of excised tissue samples and surface coil studies of intact tissue to study metabolism and time course of metabolic impairment. We will determine the origin of the changes in T1 and T2 observed following infarct in the NMR imaging experiments. These studies will improve our understanding of the factors leading to the initiation and contributing to the propagation of vasoocclusive crisis associated with sickle cell anemia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL037212-01
Application #
3352739
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461