sent study. Control animals received similar volumes of 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. Premature atrial contractions were more frequently observed in Fabry KO mice than WT mice. Heart weight was increased for Fabry KO mice, compared to WT mice when normalized to body weight or tibial TG-02 supplier length.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. doi:10.1371/journal.pone.0033743.t001 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 identical myocyte diameters, and electron micrographs showed occasional electron dense lamelated inclusion bodies, similar to previous descriptions .Staining with Picrosirius Red showed no significant differences in non-vascular collagen staining in the myocardium of male Fabry KO mice compared 15950465” 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 24171924” 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 natriuretic peptide, plasminogen activator inhibitor-1; connective tissue growth factor, thrombospondin 1, and thrombospondin 2.
