Reversible Myocardial Dysfunction in HIV‐Tat Transgenic Mouse

Potential mechanisms responsible for myocardial dysfunction in HIV infection include direct effects of HIV proteins (e.g. gp120, tat). We have previously reported evidence that cardiac myocyte‐specific expression of HIV‐Tat (Tat) results in a murine cardiomyopathy model. We now report that cardiac myocytes isolated from Tat exhibit shortened anatomical and functional survival in vitro (i.e. <40 min vs >120 min; p<.01), decreased ATP levels, (p<.01) decreased GSH (reduced glutathione;p<.01); decreased GSH/GSSG (p<.01) and blunted positive (%Fractional shortening; +dl/dt) and negative (−dl/dt) inotropic responses to Ca++ (p<.01, for each). Treatment of Tat cardiac myocytes with the sulfhydryl donor, N‐acetylcysteine (NAC) dose‐dependently reversed both the positive and negative inotropic defects in Tat; normalized duration of contractile function from <40 min to >120 min; increased GSH (p<0.01); ratio of GSH/GSSG (p<0.01) and normalized the blunted dose response to Ca2+ (p<0.01). Thus, cardiac myocyte expression of Tat results in a phenotype of reversible myocardial dysfunction. Elucidating the basic mechanisms responsible for this Tat cardiomyopathy model should contribute to a better understanding of the basic mechanisms involved in myocardial dysfunction in HIV, as well as, other cardiomyopathies in animal models and humans.