We hope to clarify the molecular events occurring during cardiovascular injury by continuing our experimental work on the potent cardiovascular toxin, allylamine, and expanding our laboratory's work to in vitro cell culture systems, the investigation of myocardial ischemia, and other cardiovascular toxins. To further study allylamine (AA), we will isolate and definitively identify its hypothesized urinary metabolites, study the hypothetical role of Benzylamine oxidase and the monoamine oxidase systems by histochemical, ultracytochemical, and biochemical means in our acute and chronic rat models of AA cardiovascular toxicity. Continued morphologic studies of AA lesions will focus on acute endothelial and smooth muscle effects, using H3-Thymidine to assess hypothetical nuclear activation by AA's toxic metabolite, acrolein. Applying our methods of cardiovascular toxicology to endothelial smooth muscle, and possibly myocardial cell culture systems, we will investigate the metabolism of AA, toxicity of its metabolites, and we will attempt to assess metaplasia induced in these systems in parallel to the in vivo cartilagenous and bony metaplasia we have observed. Glutathione - both reduced and oxidized - and glutathione peroxidase, transferase and reductase will be studied in an ischemic myocardial dog model. Continued basic morphologic and toxicologic studies of other aliphatic amines, and other cardiotoxic compounds will be done.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026189-10
Application #
3338506
Study Section
Pathology A Study Section (PTHA)
Project Start
1980-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
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