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Ergically driven, we compared the fourth ECG tracing of a R13 strongly reactive animal Fig. 7A ; with that of a naive mouse after i.p. administration of isoproterenol Fig. 7B ; . The similarity between the recordings in Fig. 7 TcP2 and isoproterenol ; show clearly that anti-R13 specificities with adrenergic-stimulating activity exert a catecholamine-like effect, resulting in supraventricular tachycardia analogous to that induced by isoproterenol. Correlation between ECG disturbances and prevalence of anti-P013 and -R13 antibodies with a marked adrenergic-stimulating activity Analysis of the variations in the levels of functional anti-P013 and -R13 antibodies during the immunization protocol and the corresponding changes in the ECGs, accompanied by death in the case of TcP2 , revealed significant associations. Anti-P013 antibodies were measured as early as the third bleed 52 days after the beginning of the protocol ; , with antibody titers reaching 1: 1600 in one case. However, no changes in the ECG were recorded. This trend was maintained 2 wk later, with the exception of mouse 38, which presented a high anti-P013 titer 1: 6400 ; and an ECG pattern of abnormal repolarization. The remaining TcP0 immunized mice the majority with titers ranging between 1: 1600 and 1: 6400 ; had normal ECGs Table 2 ; . The last ECG recording and bleed were performed 2, 5 wk later. By that time, 70% of the 10 anti-P013-positive mice presented electrogenic or conduction disturbances in their ECG Tables 2 and 3 ; . All mice with 1: 12800 anti-P013 antibody titers presented either supraventricular arrhythmia or abnormal repolarization, whereas first degree AV block was recorded in mouse 31 Table 2 ; , evolving from a 1: 3200 to a 1: 6400 titer. Another mouse with supraventricular arrhythmia mouse 32, Table 2 ; evolved similarly whereas mice 30 and 39 maintained a normal ECG tracing. Considering there were two TcP0 immunized mice negative for anti-P013 antibodies with normal ECGs, a significant association between high anti-P013 antibody levels and altered ECG recordings was evident Fig. 8A, P 0.001 ; . Since the levels of antibodies against the complete TcP0 protein were similar in both groups, the recordANTI-P ANTIBODIES ARE PATHOGENIC.
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