As shown in the experimental scheme in Figure 1A, after 60 min ischemia, rats were treated with different doses of WK or a positive control drug Met for 14 days. ECG from Sham, Model, WK-L, WK-M, WK-H, and Met-treated groups (Figure 1B) indicated that cerebral ischemia caused clear arrhythmia, which was suppressed by Met or WK in a dose-dependent manner. Optical action potential (AP) traces shown in Figure 1C further demonstrated sinus rhythm and circular reentry abnormality after ischemic stroke, while Met or WK improved it in a dose-dependent manner. Similarly, S1S1 activation caused Model rat hearts to exhibit more frequent atrial tachycardia (AT)/AF (Sham = 4.60 ± 4.10 vs. Model = 27.67 ± 11.02, P < 0.01, Figure 1E) and decrease the atrial effective refractive period (AERP)/APD (Sham = 1.50 ± 0.06311 vs. Model = 0.71 ± 0.06, P < 0.01, Figure 1D), which was reduced after treatment with WK-L, WK-M, WK-H, and Met to 0.80 ± 0.05 (P > 0.05), 0.90 ± 0.08 (P < 0.01), 1.10 ± 0.12 (P < 0.01) and 1.14 ± 0.07 (P < 0.01), respectively. In contrast to Sham rats, Model rats had a significantly longer overall AT/AF duration (P < 0.01 or P < 0.05) and a higher likelihood of inducing AT/AF (P < 0.01 or P < 0.05). In addition, Model rats also reduced susceptibility to AF. The percentage of Model rats that had AF started to appear at 70 ms, and when the frequency increased, the incidence of AF in the Model rats persisted. However, WK-L, WK-M, WK-H and Met groups exerted an anti-arrhythmic function by reducing AT/AF duration (WK-L = 5.00 ± 4.59, P < 0.01; WK-M = 11.00 ± 6.56, P < 0.05; WK-H = 3.00 ± 1.00, P < 0.01 and Met = 6.33 ± 3.51, P < 0.01), and increasing the AERP/APD susceptibility (P < 0.01 or P < 0.05, Figures 1D-F).
Figure 1. Ischemic stroke caused atrial arrhythmia that was suppressed by WK. (A) Timeline of the MCAO operation, drug treatment, and the following ex vivo cardiac optical mapping. (B) Representative ECG recordings of isolated heart during sinus rhythm. (C) Representative images of conduction in Sham, Model, WK-L, WK-M, WK-H and Met groups under the burst pacing at S1S1. (D) AERP/APD of each group. (E) Statistical results of AF duration in each group. Values were expressed as mean ± SD (n=3-5, *P < 0.05 and **P < 0.01, Model vs. Sham; #P < 0.05 and ##P < 0.01, Model vs. WK) (F) Incidence of atrial ectopy or fibrillation for each S1 interval. (G) Sinus node recovery duration of each group under different stimulation frequencies (100-50 ms). Values were expressed as mean ± SD ).
Theranostics. 2024 Oct 7;14(17):6625-6651.
doi: 10.7150/thno.99065. PMID: 39479451; PMCID: PMC11519791.
