The greater susceptibility to arrhythmogenic alternans in spontaneously hypertensive rats (SHR) is associated with remodeling of T-Tubule network

DI MARZIO GD; MARIANGELO JIE; GONANO L; SAID M; MUNDIÑA - WEILENMANN C

Mendoza

Congreso; Congreso anual de la International Society for Heart Research Latinamerican Section; 2023

International Society for Heart Research (ISHR) Lat Section y Federación Argentina de Cardiología

At the cellular level, cardiac alternans described the cyclic beat-to beat fluctuations on action potential duration, calcium (Ca) transient amplitude and contraction. Clinically, cardiac alternans manifests as alternation of the T-wave on the ECG and predisposes individuals to arrhythmia and sudden cardiac death. We have previously reported that the hypertrophied myocardium of the spontaneously hypertensive rats (SHR) showed an increased susceptibility to cardiac alternans associated to a prolonged refractoriness of sarcoplasmic reticulum (SR) Ca release when compared with Normotensive rats (W). In heart failure, a disorganized Ttubule (TT) network contributes to a dyssynchronous SR Ca release and an impaired excitation-contraction-coupling (ECC). The aim of our work was to study the role of TT organization on the premature appearance of alternans in SHR hearts. To visualize TT, myocytes from 6 mo Wand SHR were stained with Di-8-ANEPPS. Confocal microscopy images were quantitativelyanalyzed using two programs: TTorg plugin from ImageJ and Tubulator. Expression ofjunctophilin-2 (JPH2) and caveolin-3 (Cav3), two proteins involved in the structure and maintenance of the TT system, was analyzed by Western Blot. SHR myocytes showed astructural remodelling of the TT network, with TT loss at discrete and local regions incomparison with W myocytes. The peak power value, used as a quantitative index of TTintegrity, decreased in SHR myocytes (57.11 ± 0.74 vs. W: 63.11 ± 1.99 a.u. n=18-38 from 2-5hearts). A further analysis of the geometrical organization of the TT system revealed a greaterfraction of longitudinal vs. transverse components in SHR myocytes (SHR: 84.36 ± 0.61 and15.64 ± 0.61 % vs. W: 87.22 ± 0.6 and 12.78 ± 0.6 % for transverse and longitudinal components respectively, n= 18-36 cells from 2-5 hearts, P