Core--Morphology and pathophysiology

Washington University, Saint Louis MO

Investigators

Linked publications & trials

Abstract

The objectives of the Pathophysiology and Morphology Core are to simulate in animals the pathophysiology of diabetes in humans and to characterize the functional, metabolic, and morphologic phenotypes of transgenic animals needed to bridge fundamental metabolic and genetic insights with the pathogenesis of the disease. These objectives will e accomplished while interacting with the component projects by inducing and monitoring diabetes in mice and rats; by measuring the hemodynamics, ventricular function, and metabolism of hearts from transgenic mice; by analyzing the morphology and cell types of hearts and vessels from animals as well as the subcellular distribution of peroxisomes and PLA2 isoforms in myocardium; and by assessing arrhythmogenesis during induction of myocardial ischemia or infarction. The revised Core is more focused and substantially strengthened by emphasizing a comprehensive approach to cardiac physiologic and metabolic phenotyping combined closed-chest 2-D echocardiography and hemodynamic measurements, recordings of electrograms and programmed electrical stimulation of isolated hearts, ambulatory telemetric electrocardiography of intact animals, and metabolism in isolated working hearts. Since the original application was submitted, we have gained considerable experience with each of these methods and have now done echocardiography and catheterization on over 100 mice, programmed electrical stimulation on 20 mouse hearts, ambulatory telemetric monitoring over 60 mice, and over 50 isolated, working mouse hearts. The Core will take advantage of and interact with existing specialized research units at Washington University School of Medicine including the Digestive Disease Research Core, which has facilities for preparation of paraffin-embedded tissue sections and routine histology; the Clinical Nutrition Research Unit-Animal Model Research Core, which has facilities for quantitative microscopy; and the Department of Pathology confocal and electron microscopic facilities. Results obtained from the Core will permit characterization of the cardiac phenotypes of several novel transgenes as well as facilitate understanding of pathophysiologic and morphologic links between diabetes and the metabolism of lipids in clinically relevant animal preparations.