Over‐expression of HIV Tat Results in both Systolic and Diastolic Dysfunction in Awake Mice

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Mechanisms responsible for HIV cardiomyopathy are unknown, but may include direct effects of HIV proteins on the heart. Transgenic mice overexpressing HIV Tat protein targeted to the myocardium, +/−Tat high transgenic mice (TG), have revealed anatomical and biochemical defects in the heart. The present studies were conducted to clarify the effect of Tat on cardiac function. In vivo hemodynamics were measured in awake mice after inserting a catheter tip in the left ventricle under general anesthesia. Under the age of three month, the heart rate (HR) was significantly lower in TG (591¡À47 vs 716¡À45 bpm, TG vs Control, respectively (p<0.05;n=8–12). Other hemodynamic indexes, including left ventricular systolic pressure (LVSP), positive and negative dp/dt (mmhg/s), and left ventricular end diastolic pressure (LVEDP) remained indistinguishable from Control. At 6 mos, however, ventricular dysfunction was evidenced in TG (HR = 580¡À47 vs 673¡À25 bpm, TG vs Control, p<0.05); LVSP (132¡À6 mmhg vs 147¡À6 mmhg, TG vs Control; p<0.05); LVEDP (15¡À4 mmhg vs 8¡À6 mmhg, TG vs Control, p<0.05); +dp/dt= 8872¡À331 mmhg/s vs 10026¡À796 mmhg/s TG vs Control, p<0.01) and .Cdp/dt (7403¡À432 mmhg/s vs 8835¡À368 mmhg/s, TG vs Control, p<0.01; n=8–12 in each group). Thus, targeted myocardial transgenic expression of HIV Tat results in depression in both systolic and diastolic function in mice.