The duration of AF was shortened substantially in mice administered iloprost compared with vehicle-treated mice following Ang II infusion (Ang II+vehicle: 2.962±0.081 s versus Ang II+iloprost: 1.747±0.092 s) (Fig. 2f). There was no significant difference in the inducibility of AF between the saline groups, with or without iloprost (2/11 for saline+vehicle versus 1/11 for saline+iloprost) (Fig. 2e and f). Next, we recorded the electrical conduction mapping of the LA in vivo. LA electrical conduction in saline-infused mice, with or without iloprost, was uniform and showed an orderly spread to the surrounding tissue (Fig. 2g). However, LA electrical conduction in Ang II-infused mice was disordered,and there were abnormal positions in the wave conduction, which was restored after iloprost treatment (Fig. 2g). The left atrial conduction velocity was significantly lower in Ang II-infused mice and improved in the presence of iloprost (Fig. 2h). Moreover, LA conduction dispersion was increased in Ang II-infused mice and reduced in iloprost-treated mice (Fig. 2i).

 

 

Fig. 2 PGI2(prostaglandin I2) analog iloprost reduced Ang II (angiotensin II)-induced AF (atrial fibrillation) inducibility. a, C57BL/6J mice were housed with or without infusion of Ang II (2000 ng/kg/min) for 28 days. Starting on the 15th day of infusion, iloprost (0.2 mg/kg/ day) or vehicle were supplied for a period of 14 days. b and c, Noninvasive tailed-cuff monitoring of SBP (systolic blood pressure, b) and DBP (diastolic blood pressure, c) of Saline/Vehicle, Saline/Iloprost, Ang II/Vehicle, and Ang II/Iloprost mice. d, Representative surface ECG (electrocardiogram) tracing during burst pacing (BP) is depicted within the black box. Red dashes denote AF, and green dashes denote sinus rhythm (SR). e, Fraction of animals with successful AF induction. Ratios represent the number of AF induced to total animals. n=11 per group, Fisher exact test. f, Violin plot of AF in animals (numbers for each group are shown in e). g, Representative epicardial electrical conduction activation maps of the left atrium. The color bar on the right side of the image represents the conduction proceeding advancing from 0 ms (dark red) to the end of imaging period (5 ms, blue). The arrows indicate the direction of conduction. Scale bar, 0.4 mm. h, Summary of CV (conduction velocity) in the left atrium. i, Summary of inhomogeneity index in the left atrium. Two-way ANOVA, n=8–11 mice per group, * P<0.05, **P<0.01

 

Cellular and Molecular Life Science

https://doi.org/10.1007/s00018-024-05259-3