Objective: To investigate the effects of sympathetic nerve stimulation (SNS) on connexin43 (Cx43) and ventricular arrhythmias during acute myocardial ischemia (MI).
Methods: Ninety five Wistar rats were randomly divided into four groups: MI group (n=25), undergoing: ligation of the anterior descending coronary; MII-SNS group (n=25); undergoing electric stimulation of sympathetic nerve since the beginning of ligation of the anterior descending coronary and lasting till 30 min after the ligation, sympathetic nerve stimulation preconditioning + myocardial ischemia (pSNS-MI) group (n=25), undergoing electric stimulation of sympathetic nerve since the beginning of ligation of the anterior descending coronary that ended just after the ligation; and sham operation (SO) group (n=20), without coronary ligation. Ventricular arrhythmias were monitored by electrocardiography. Western blotting and RT-PCR were used to detect the protein and mRNA expression of Cx43 respectively. Immunofluorescence analysis was used to observe the changes of Cx43 protein distribution.
Results: One and 3 rate died due to ventricular fibrillation in the MI group and MI-SS group respectively. The incidence of ventricular tachycardia (VT)/VF within 30-minute after ligation in the MI-SNS group was 80.0%, significant higher than that of the MI group (52.0%, P < 0.05). The incidence of VT/VF within 30-minute after ligation of the pSNS-MI group was 20.0%, significantly lower than that of the MI-SNS group (P < 0.05). 30 minutes after the ligation, the percentage of phosphorylated Cx43 of the pSNS-MI and MI-SNS groups were 71.2% +/- 7.0% and 73.4% +/- 6.7% respectively, both significantly higher than that of the MI group (46.7% +/- 6.3%) (both P < 0.05). The total contents of Cx43 of the MI and pSNS-MI groups were 1.29 +/- 0.14 and 1.25 +/- 0.13 respectively, both similar to that of the SO group [(1.30 +/- 0.10), both P > 0.05], while the total Cr43 content of the MI-SNS group was 0.73 +/- 0. 12, significantly lower than that of the SO group [(1.30 +/- 0.10), P < 0.05]. The Cx43 mRNA levels of the 3 experimental groups were all significantly lower than that of the SO group (all P < 0.05). Immunofluorescence analysis confirmed that ischemia and sympathetic nerve stimulation induced the changes of connexin43 distribution and sympathetic nerve stimulation preconditioning inhibited the changes of connexin43 distribution induced by ischemia.
Conclusion: SNS promotes ventricular arrhythmias by promoting Cx43 degradation, and sympathetic nerve stimulation preconditioning inhibits ventricular arrhythmias by preventing Cx43 dephosphorylation.