Core--Mouse cardiac physiology

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This core unit will be available to all investigators on the UCSD SCOR and will apply and improve miniaturized hemodynamic, imaging and microsurgical techniques for in vivo and in vitro physiological and morphological studies in mice, or larger rodents as needed (rats, hamsters), in order to fully characterize cardiac phenotypes. Miniaturized imaging techniques for determining cardiac morphology and function include transthoracic ultrasound (2-D, M-mode and Doppler echocardiography) and x-ray videoangiography, and intravital videomicroscopy. Hemodynamic methods include high-fidelity catheter tip micromanometry and cardiac volume measurements by the conductance method for assessing intracardiac pressures, pressure-volume measurements by the conductance method for assessing intracardiac pressures, pressure volume relations and myocardial contractility, as well as diastolic function of the left ventricle (LV), in anesthetized closed- chest animals using retrograde LV catheterization via the carotid artery. A method is under development for chronic LV catheterization in chronically instrumented conscious mice. Microsurgical techniques have been developed in mice to produce chronic pressure overload on either the left or right ventricle which can be used to stimulate hypertrophy or to induce heart failure. Microsurgical gene transfer methods are being developed and will be available in the adult animal (mice and larger rodents). Finally, characterization of myocardial tissue, myocardial cells or cultured tissue will be accomplished by standard histologic methods, including confocal microscopy and electron microscopy, Evans blue dye and wheat germ agglutinin staining to assess sarcolemmal integrity, and immunostaining of various proteins, including transmembrane extracellular matrix and cytoskeletal proteins.