Abstract 19511: Progesterone Reduces Isoproterenol-Induced pVTs in Male Transgenic Long QT Syndrome 2 (LQT2) Rabbits

Background: During childhood, boys with long QT syndrome (LQT) have a higher risk than girls for developing ventricular arrhythmia and sudden cardiac arrest. We have previously shown a pro-arrhythmic effect of estrogen (EST) and an anti-arrhythmic effect of progesterone (PROG) in transgenic female LQT2 rabbits. Here we study the effects of sex hormones in male LQT2 rabbits; hypothesizing that orchiectomy (ORCH) will increase the arrhythmogenic risk as compared to treatment with PROG or dihydrotestosterone (DHT). Methods: Orchiectomized LQT2 males were implanted with 90-day release pellets containing PROG (n=6), DHT (n=5), or placebo (ORCH) (n=6). All groups underwent dual voltage-calcium optical mapping ex vivo after 8 weeks of hormone-treatment. Results: During 8 weeks of hormone-treatment, no episodes of SCD occurred in any groups. Optical mapping revealed similar APD and APD dispersion in all groups (APD, ms, ORCH 239.9±29.2, DHT 251.4±15.7, PROG 253.0±19.9) (APD dispersion, ms, ORCH 30.7±6.8, DHT 33.1±5.70, PROG 34.1±6.0). Isoproterenol induced calcium and voltage oscillations during the second phase of the AP in all three groups (Fig.1), However, the duration of the induced pVT was longer in ORCH rabbits as compared to PROG (5.8±4.8 sec vs. 2.1±1.3 sec p Conclusion: Orchiectomy sensitized male LQT2 rabbits to isoproterenol-induced arrhythmias. PROG reduced the duration of pVT, but did not uncouple calcium and voltage oscillations as it does in ovariectomized female LQT2 rabbits.