Figure 4.
Overstimulation of IL-6 trans-signaling induces QT prolongation in guinea pigs under conditions of cardiac challenge. (A) Experimental protocol used to assess the effect of the overstimulation of IL-6 trans-signaling on guinea pig QT interval induced by recombinant IL-6 and sIL-6R injected into the cranial vena cava (CVC). (B) Representative traces of surface ECG recorded in IL-6-sIL-6R (Top panel) and untreated control (Bottom panel) guinea pigs. The subsequent exposure to the β-adrenergic receptor agonist ISO in the continued presence of IL-6-sIL-6R triggered ventricular arrhythmias (C,D). Averaged mRNA expression of KCNQ1 (E) and KCNE1 (F) measured in LFD and HFD ventricular tissue samples (n = 4 LFD, 5 HFD). Data are expressed as the fold change in expression compared with LFD after normalization to GAPDH. Our data revealed severely reduced expression of KCNQ1 and KCNE1 coding for IKs in HFD ventricular samples, in agreement with dramatic ventricular electrical remodeling and increased risk of exercise-induced VT. Data columns represent mean ± S.E.M from n = 4–5 guinea pig/group, * Statistical significance at p < 0.05.