The continuing objective of the research proposed in this renewal application remains the elucidation of the biochemical mechanisms that lead to irreversible cell injury in ischemia. Based on the progress reported below during the first 4 years of support from this grant, a working hypothesis of the sequence of events mediating the loss of cell viability in, at least, liver ischemia has been derived.
The specific aims of the studies proposed here are 1) to further assess the validity of this hypothesis and 2) to evaluate its relevance to the mechanisms of ischemic cell injury in general and to ischemic myocardial cell injury in particular.
The first aim will be addressed by consideration of a) the role of the release of intracellular, sequestered calcium stores in the genesis of membrane injury; b) the respective roles of an accelerated deacylation versus inhibited reacylation in the net loss of phospholipid; c) the relationship between such a mechanism for lipid depletion and the redistribution of intracellular Ca++ ion stores; d) the further analysis of the consequences of phospholipid loss with respect to the structure of cellular membranes; and 3) the changes in the structure and function of the plasma membrane. Two established experimental models are to be used: 1) in situ ischemia of the intact rat liver and 2) the anoxic death of cultures rat hepatocytes.
The second aim will concentrate initially on the sarcolemma of ischemic myocardium with particular attention to the role of phospholipid degradation and consequent changes in membrane structure and function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037764-02
Application #
3353746
Study Section
Pathology A Study Section (PTHA)
Project Start
1986-05-01
Project End
1990-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107