The propensity to atrial arrhythmia was also assessed in isolated hearts using optical mapping and S1S2 stimulation. Representative optical AP traces and corresponding ECG are shown in Figure 3, A–C, which illustrates a range of arrhythmic responses observed in a vehicle rat. Of note, activation map analyses of the induced AF show atrial ectopy and reentry circuit. Compared with sham rats, the hearts of vehicle-treated rats exhibited more frequent atrial ectopy or fibrillation in response to S1S2 stimulation, which was prevented after treatment with GSK2193874 (Figure 3D). However, no difference in atrial effective refractory period (AERP) was detected (Figure 3E)

Figure 3. Blockage of TRPV4 suppresses atrial arrhythmia propensity in isolated hearts. (A–C) Representative optical action potential (AP) and ECG recorded in a vehicle rat, showing atrial ectopy (B), fibrillation (C), and neither ectopy nor fibrillation (A) induced by using an extrastimulus (S1S2; S2 intervals ranging from 50 to 30 ms) method. (C) Activation maps of pacing, ectopy, reentry, and sinus rhythm corresponding to the AP traces. (D) Incidence of atrial ectopy or fibrillation for each S2 interval in the 3 groups; sham, n = 10; vehicle, n = 11; GSK2193874, n = 7. Statistical analyses: χ2 test; *P < 0.05, **P < 0.01 versus sham. (E) Quantification of atrial effective refractory period in the 3 groups; sham n = 8; vehicle n = 8; GSK2193874 n = 7. Statistical analyses: 1-way ANOVA with Bonferroni’s post hoc test. Data are expressed as the mean ± SEM.

JCI Insight. 2020 Dec 3;5(23):e137528.

doi: 10.1172/jci.insight.137528. PMID: 33119551; PMCID: PMC7714415.