Abstract 208: Rotigaptide Remodels Connexin 43 Expression in a Prolonged Ventricular-Fibrillation in Swine
Introductions: Connexin 43 (Cx43) is a connexin that formulate the gap junctions (GJs), which are important channels for electrical impulse conducting and signal molecular transmitting. During the course of ventricular fibrillation (VF), an increasing reduction in the expression of Cx43 at the gap junction (GJ) was observed. Rotigaptide (ZP123) is a novel antiarrhythmic peptide that reduced the inducibility of re-entry ventricular tachycardia via enhancing cell-to-cell coupling.
Hypothesis: We assessed the hypothesis that ZP123 would reverse the expression and/or distribution changes of Cx43 during VF, therefore preventing or treating VF. Interventions: Thirty domestic pigs were anesthetized and assigned in three groups in a randomized fashion: Group 1, ZP123 group (ZP123 1μg/kg bolus + 10μg/kg/h pumped by a micro pump for 15min); Group 2, control group (the same dose as Group 1 but only saline), Group 3, sham group, (treated with sham operation). Drugs and saline were used 15min before VF started. VF was induced in ZP123 group and control group, but not sham group. After 8 min of untreated VF, cardiopulmonary resuscitation (CPR) was performed according to the 2005 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care . Animals survived for 1 hour were euthanized with intravenous injection of KCL and the ventricular samples of these animals were separated for immunofluorescence analysis and Western blot analysis of Cx43 protein.
Measurements and Main Results: Both immunofluorescence and Western blot analysis show that the level of Cx43 expression in ZP123 group was significantly higher than control group (1.71±0.06 vs. 1.58±0.1; 1.108±0.146 vs. 0.713±0.163, P<0.05 respectively), while comparable with sham group (1.71±0.06 vs. 1.76±0.08; 1.108±0.146 vs. 1.171±0.148, P>0.05 respectively). The average defibrillation energy in ZP123 group was much lower than control group (325±130J vs. 4851±49J, P<0.05).
Conclusions: Pretreatment with ZP123 increased the expression of Cx43 and lowered the defibrillation energy in the long-term VF pig model. ZP123 could be a good candidate for the treatment of VF. Figure 1. Immunofluorescence analysis Figure 2. Western blot analysis of Cx43
- © 2010 by American Heart Association, Inc.