BACKGROUND: Increased cardiac sympathetic nerve activity is thought to contribute to ventricular tachyarrhythmias during acute myocardial ischemia (MI). However, the mechanism is not completely understood. This study investigated the effects of sympathetic nerve stimulation (SNS) on ventricular tachyarrhythmias and connexin43 (Cx43) during acute MI in rats. METHODS: Ninety five male Wistar rats were randomly assigned into four groups receiving the following treatments: myocardial ischemia with sympathetic nerve stimulation (MI-SNS, n=25), sham-operation treated with sham stimulation (SO, n=20), myocardial ischemia with sham stimulation (MI, n=25), myocardial ischemia pretreated with sympathetic nerve stimulation (pSNS-MI, n=25). RESULTS: During the 30-min ischemia, the incidence of ventricular tachyarrhythmias, i.e., ventricular tachycardia or ventricular fibrillation (VT/VF) was increased in the MI-SNS group and decreased in the pSNS-MI group compared to that in the MI group (p<0.05 for both). The total amount of Cx43 protein was significantly decreased in the MI-SNS group but not in the MI group and the pSNS-MI group. The amount of phosphorylated Cx43 in the MI-SNS group was significantly lower compared to that in the SO group and the MI group (p<0.05). However, the amount of phosphorylated Cx43 was significantly increased in the pSNS-MI group compared to that in the MI group and the MI-SNS group (p<0.05). CONCLUSIONS: SNS promoted the degradation of Cx43 protein, especially the phosphorylated Cx43 protein, whereas pSNS inhibited the ischemia-induced loss of phosphorylated Cx43 during acute MI. These changes may be related to the pro- or anti-arrhythmic effect of SNS or pSNS during acute MI.
BACKGROUND: Increased cardiac sympathetic nerve activity is thought to contribute to ventricular tachyarrhythmias during acute myocardial ischemia (MI). However, the mechanism is not completely understood. This study investigated the effects of sympathetic nerve stimulation (SNS) on ventricular tachyarrhythmias and connexin43 (Cx43) during acute MI in rats. METHODS: Ninety five male Wistar rats were randomly assigned into four groups receiving the following treatments: myocardial ischemia with sympathetic nerve stimulation (MI-SNS, n=25), sham-operation treated with sham stimulation (SO, n=20), myocardial ischemia with sham stimulation (MI, n=25), myocardial ischemia pretreated with sympathetic nerve stimulation (pSNS-MI, n=25). RESULTS: During the 30-min ischemia, the incidence of ventricular tachyarrhythmias, i.e., ventricular tachycardia or ventricular fibrillation (VT/VF) was increased in the MI-SNS group and decreased in the pSNS-MI group compared to that in the MI group (p<0.05 for both). The total amount of Cx43 protein was significantly decreased in the MI-SNS group but not in the MI group and the pSNS-MI group. The amount of phosphorylated Cx43 in the MI-SNS group was significantly lower compared to that in the SO group and the MI group (p<0.05). However, the amount of phosphorylated Cx43 was significantly increased in the pSNS-MI group compared to that in the MI group and the MI-SNS group (p<0.05). CONCLUSIONS: SNS promoted the degradation of Cx43 protein, especially the phosphorylated Cx43 protein, whereas pSNS inhibited the ischemia-induced loss of phosphorylated Cx43 during acute MI. These changes may be related to the pro- or anti-arrhythmic effect of SNS or pSNS during acute MI.
Authors: Rebecca-Ann B Burton; Jakub Tomek; Christina M Ambrosi; Hege E Larsen; Amy R Sharkey; Rebecca A Capel; Alexander D Corbett; Samuel Bilton; Aleksandra Klimas; Guy Stephens; Maegan Cremer; Samuel J Bose; Dan Li; Giuseppe Gallone; Neil Herring; Edward O Mann; Abhinav Kumar; Holger Kramer; Emilia Entcheva; David J Paterson; Gil Bub Journal: iScience Date: 2020-07-01