Limits...
Effects of rotigaptide (ZP123) on connexin43 remodeling in canine ventricular fibrillation.

Su GY, Wang J, Xu ZX, Qiao XJ, Zhong JQ, Zhang Y - Mol Med Rep (2015)

Bottom Line: Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05).Cx43 expression was higher in the 12-min and 30-min ZP123 groups than that in the NS control group (P<0.05), while p-Cx43 expression decreased, although the levels were significantly higher than those in the control groups (P<0.05).Cx43 expression was positively correlated with the defibrillation success rate (r=0.91; P<0.01) and negatively with the mean defibrillation energy (r=-0.854; P<0.01), while p-Cx43 expression was positively correlated with the success rate of the previous three defibrillations (r=0.926; P<0.01).In conclusion, ZP123 reduced Cx43 remodeling through regulating the expression, distribution and phosphorylation of Cx43, thereby reducing the defibrillation energy required for successful cardioversion.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

ABSTRACT
The present study investigated the effects of rotigaptide (ZP123) on the expression, distribution and phosphorylation of connexin43 (Cx43) in myocardial cell membranes in cardioversion of ventricular fibrillation (VF). A model of prolonged VF (8, 12 and 30 min) was established in mongrel dogs (n=8/group), following treatment with ZP123 or normal saline (NS control). A sham control was included. Cardiopulmonary resuscitation was begun at the start of VF followed by defibrillation. Animals received a maximum of three defibrillations of increasing energy (70, 100 and 150 J biphasic shock) as required. The average defibrillation energy, defibrillation success rate, return of spontaneous circulation and survival rate were recorded. Cx43 and phosphorylated (p-)Cx43 expression in cardiomyocyte membranes was detected by western blot and immunofluorescence analyses. Compared with the NS-treated control groups, the success defibrillation rate in the 8-min and 12-min ZP123 groups was significantly higher (P<0.05), while the average defibrillation energy was significantly lower (P<0.05). Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05). Cx43 expression was higher in the 12-min and 30-min ZP123 groups than that in the NS control group (P<0.05), while p-Cx43 expression decreased, although the levels were significantly higher than those in the control groups (P<0.05). Cx43 expression was positively correlated with the defibrillation success rate (r=0.91; P<0.01) and negatively with the mean defibrillation energy (r=-0.854; P<0.01), while p-Cx43 expression was positively correlated with the success rate of the previous three defibrillations (r=0.926; P<0.01).In conclusion, ZP123 reduced Cx43 remodeling through regulating the expression, distribution and phosphorylation of Cx43, thereby reducing the defibrillation energy required for successful cardioversion.

Show MeSH

Related in: MedlinePlus

Western blot analysis of Cx43, p-Cx43 and β-actin. Values are expressed as the mean ± standard error of the mean. *P<0.05 vs. sham control; 2P<0.05 vs. the corresponding control NS group. β-actin was used as loading control. p-Cx43, phosphorylated Cx43; ZP123, rotigaptide; VF, ventricular fibrillation; NS, normal saline; Cx, connexin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4581824&req=5

f2-mmr-12-04-5746: Western blot analysis of Cx43, p-Cx43 and β-actin. Values are expressed as the mean ± standard error of the mean. *P<0.05 vs. sham control; 2P<0.05 vs. the corresponding control NS group. β-actin was used as loading control. p-Cx43, phosphorylated Cx43; ZP123, rotigaptide; VF, ventricular fibrillation; NS, normal saline; Cx, connexin.

Mentions: Western blot analysis showed that Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05). Cx43 expression was higher in the 12-min and 30-min ZP123 groups compared with that in the control groups (P<0.05), while no difference was detected in the 8-min groups. With the duration of VF, p-Cx43 expression decreased, while p-Cx43 in the ZP123 groups was significantly higher than that in the control groups (P<0.05). Furthermore, the ratio of p-Cx43/Cx43 decreased, while the p-Cx43/Cx43 ratio in the ZP123 groups was significantly higher than that in the control groups (P<0.05) (Fig. 2A–D).


Effects of rotigaptide (ZP123) on connexin43 remodeling in canine ventricular fibrillation.

Su GY, Wang J, Xu ZX, Qiao XJ, Zhong JQ, Zhang Y - Mol Med Rep (2015)

Western blot analysis of Cx43, p-Cx43 and β-actin. Values are expressed as the mean ± standard error of the mean. *P<0.05 vs. sham control; 2P<0.05 vs. the corresponding control NS group. β-actin was used as loading control. p-Cx43, phosphorylated Cx43; ZP123, rotigaptide; VF, ventricular fibrillation; NS, normal saline; Cx, connexin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581824&req=5

f2-mmr-12-04-5746: Western blot analysis of Cx43, p-Cx43 and β-actin. Values are expressed as the mean ± standard error of the mean. *P<0.05 vs. sham control; 2P<0.05 vs. the corresponding control NS group. β-actin was used as loading control. p-Cx43, phosphorylated Cx43; ZP123, rotigaptide; VF, ventricular fibrillation; NS, normal saline; Cx, connexin.
Mentions: Western blot analysis showed that Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05). Cx43 expression was higher in the 12-min and 30-min ZP123 groups compared with that in the control groups (P<0.05), while no difference was detected in the 8-min groups. With the duration of VF, p-Cx43 expression decreased, while p-Cx43 in the ZP123 groups was significantly higher than that in the control groups (P<0.05). Furthermore, the ratio of p-Cx43/Cx43 decreased, while the p-Cx43/Cx43 ratio in the ZP123 groups was significantly higher than that in the control groups (P<0.05) (Fig. 2A–D).

Bottom Line: Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05).Cx43 expression was higher in the 12-min and 30-min ZP123 groups than that in the NS control group (P<0.05), while p-Cx43 expression decreased, although the levels were significantly higher than those in the control groups (P<0.05).Cx43 expression was positively correlated with the defibrillation success rate (r=0.91; P<0.01) and negatively with the mean defibrillation energy (r=-0.854; P<0.01), while p-Cx43 expression was positively correlated with the success rate of the previous three defibrillations (r=0.926; P<0.01).In conclusion, ZP123 reduced Cx43 remodeling through regulating the expression, distribution and phosphorylation of Cx43, thereby reducing the defibrillation energy required for successful cardioversion.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

ABSTRACT
The present study investigated the effects of rotigaptide (ZP123) on the expression, distribution and phosphorylation of connexin43 (Cx43) in myocardial cell membranes in cardioversion of ventricular fibrillation (VF). A model of prolonged VF (8, 12 and 30 min) was established in mongrel dogs (n=8/group), following treatment with ZP123 or normal saline (NS control). A sham control was included. Cardiopulmonary resuscitation was begun at the start of VF followed by defibrillation. Animals received a maximum of three defibrillations of increasing energy (70, 100 and 150 J biphasic shock) as required. The average defibrillation energy, defibrillation success rate, return of spontaneous circulation and survival rate were recorded. Cx43 and phosphorylated (p-)Cx43 expression in cardiomyocyte membranes was detected by western blot and immunofluorescence analyses. Compared with the NS-treated control groups, the success defibrillation rate in the 8-min and 12-min ZP123 groups was significantly higher (P<0.05), while the average defibrillation energy was significantly lower (P<0.05). Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05). Cx43 expression was higher in the 12-min and 30-min ZP123 groups than that in the NS control group (P<0.05), while p-Cx43 expression decreased, although the levels were significantly higher than those in the control groups (P<0.05). Cx43 expression was positively correlated with the defibrillation success rate (r=0.91; P<0.01) and negatively with the mean defibrillation energy (r=-0.854; P<0.01), while p-Cx43 expression was positively correlated with the success rate of the previous three defibrillations (r=0.926; P<0.01).In conclusion, ZP123 reduced Cx43 remodeling through regulating the expression, distribution and phosphorylation of Cx43, thereby reducing the defibrillation energy required for successful cardioversion.

Show MeSH
Related in: MedlinePlus