The Core will manage animals (rabbits and mice) from which myocytes will be isolated at Loyola for use in all
4 of the projects. The mice used will include wild type and genetically modified mice that are developed and
bred in Core D at UCSD (including some that will be subjected to transverse aortic banding to induce
chronic pressure overload in Project by Brown). The rabbits used will include both control and heart failure (HF)
rabbits (induced by combined pressure and volume overload). The core will also be responsible for the
preparation and functional monitoring of HF rabbits during the evolution of dysfunction (under the direction
of Dr. S.M. Pogwizd at UIC). The core will also culture adult cardiac myocytes for 24-48 hours for studies
involving adenoviral gene transfer. These myocytes will be used directly by the three Loyola projects (l-lll)
for functional, imaging and biochemical analysis and also by Project by Brown for biochemical analysis (after
experimental treatment by the investigators at Loyola and shipment to UCSD). The procedures carried out
are specialized, but the personnel involved are expert in their respective roles and this should run smoothly
and efficiently in making the best use of the myocytes available.
Mice are especially valuable because of the opportunity to genetically manipulate the molecules under
investigation (and we are taking advantage of that in The Genetic Mouse Models and Adenoviruses Core) and collectively we have extensive experience
with mouse myocytes and cardiovascular disease models. The mouse work will be complemented by
studies in rabbit, where similar genetic manipulation is not practical, but rabbits are highly advantageous
here for two major reasons. First, the electrophysiological and Ca handling properties in rabbit ventricle are
very similar to that in human. Second, we have already developed a well-characterized rabbit model of
heart failure. Indeed, the HF rabbits manifest both severely depressed LV contractile function and
spontaneously-occurring ventricular arrhythmias. Rabbit myocytes are also well suited for the measurements
to be made (including: voltage clamp, fluorescence imaging, biochemical and molecular studies, and
in vitro adenoviral gene transfer. The services provided by this core are essential to the successful
completion of the science in Projects by Bers, Blatter, Mignery, and Brown, enabling the elucidation of mechanistic roles of IP3R and CaMKII in ECC, arrhythmogenesis, hypertrophy and HF.
No Sub Projects information available for 5P01HL080101-03 9001
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
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