imals received similar volumes of “ 23977191 normal saline. Mice underwent physiologic and echocardiographic assessment prior to injection, and then at 3 weeks following injection, at which point the cardiac GL-3 content was stably reduced by 80%. Statistics Data are expressed as mean 6 SE. Student’s two-tailed t tests were used to compare unpaired data between two groups. If the global test was significant, pair-wise comparisons were performed with a Tuckey-Kramer test. P 0.05 was considered significant. Results Systolic Blood Pressure, Heart Rate, ECG and Cardiac Weight Measurements Systolic blood pressure was lower for male Fabry KO mice than for male wild-type mice . In addition, heart rate was significantly slower in the Fabry KO mice than the WT controls. The measurements of RR intervals with surface ECG recordings showed prolonged RR intervals for Fabry KO mice compared to WT controls. and the standard deviations of the RR intervals were significantly increased in the Fabry KO mice compared to the WT controls after normalization for heart rate. There were no differences in PQ, QRS, or corrected QT intervals.Fabry KO mice had mild diastolic LV dysfunction as depicted with the decrease in Ea velocity, without change in the isovolumic relaxation time. Surface ECGs were obtained in lightly anesthesized mice. Data represent the means 6 SE. Statistical significance was determined by pair-wise comparisons with a Tuckey-Kramer test, or x2 analysis. WT, wild-type; KO, knockout; SDNN, standard deviation of normal RR intervals; APC, %of animals with atrial premature contractions during 10 min recording. P,0.05, P,0.05 by for x2 analysis. Left Ventricular Histologic Alteration Routine histological stains did not reveal any structural difference between 4 month-old Fabry KO and wild type mice. Morphometric analysis showed 345627-80-7 identical myocyte diameters, and electron micrographs showed occasional electron dense “25849133 lamelated inclusion bodies, similar to previous descriptions . Abbreviations: LA, left atrium; LV, left ventricle; LV EDD, left ventricular end diastolic diameter; Vcfc, velocity of shortening of circumferential fibers; Sa, Spw: maximal systolic velocity of the mitral annulus and posterior wall; IVRT: isovolumic relaxation time; Ea and Epw: maximal diastolic velocity of the mitral annulus and posterior wall; E, maximal velocity of LV inflow. Staining with Picrosirius Red showed no significant differences in non-vascular collagen staining in the myocardium of male Fabry KO mice compared to WT mice and no predominant area of fibrosis in Fabry KO mice. Systolic Blood Pressure, Heart Rate, ECG and Cardiac Weight Measurements: Effects of ERT The measurements of RR intervals with surface ECG recordings showed identical RR intervals and the standard deviation of the RR intervals, and the frequency of premature atrial contractions for Fabry KO mice compared to Fabry KO mice treated with 3 mg/kg intravenous ERT 3 weeks before. There were no significant differences in PQ, QRS, or corrected QT intervals. ERT had no effect 3 weeks after 
injection on heart weight for Fabry KO mice, when normalized to body weight or tibial length. There was no effect 3 weeks after injection on heart weight for WT mice, when normalized to body weight or tibial length. LV Molecular Alterations in Fabry KO Mice We examined myocardial alterations that could be associated with cardiac remodeling and dysfunction by analyzing mRNA expression for atrial natriuretic factor brain natriureti
