It has been argued and recent evidence demonstrates that taurine is physiologically important to the cardiocyte. The objectives of this proposal are to further characterize a model of myocardial failure associated with taurine deficiency in domestic cats. This model will then be utilized to study the effects of taurine depletion on myocardial function in vivo and in vitro. In phase I, the candidate will pursue related didactic and laboratory instruction.
Specific aims will include: 1) characterizing the natural history of taurine depletion myocardial failure (TDMF) with regard to rate of onset while feeding purified diets; 2) correlating tissue taurine concentrations with degree of myocardial failure; 3) validating techniques for obtaining measures of ventricular function (dP/dt and end-systolic pressure diameter relationships) in cats; 4) utilizing nuclear magnetic resonance spectroscopy for in vivo examination of cardiac bioenergetics; and 5) studying alterations in myocyte contractile proteins by gel electrophoresis and contractility by laser diffraction in cultured feline cardiocytes. In phase II, specific aims will include demonstrating the interrelationship between the effects of taurine depletion and induced pathologic stimuli for cardiac hypertrophy utilizing a model of eccentric (mitral regurgitation) and concentric (aortic banding) hypertrophy. The methods developed in phase I will be utilized to compare normal, TDMF, hypertrophied TDMF and hypertrophied taurine fed animals. Feline dilated cardiomyopathy (DCM) is caused by taurine depletion and is functionally similar to DCM in humans. TDMF cats may provide a useful model for studying cellular pathways modulating myocardial function and for testing pharmaceuticals with potential inotropic effects. Furthermore, elucidation of mechanisms by which taurine influences cardiac inotropy may lead to new concepts regarding modulation of myocardial function in diseased hearts.
|Pion, P D; Kittleson, M D; Skiles, M L et al. (1992) Dilated cardiomyopathy associated with taurine deficiency in the domestic cat: relationship to diet and myocardial taurine content. Adv Exp Med Biol 315:63-73|
|Pion, P D; Kittleson, M D; Rogers, Q R et al. (1990) Taurine deficiency myocardial failure in the domestic cat. Prog Clin Biol Res 351:423-30|