Abstract 18992: Kappa Opioid Receptor Improves Postresuscitation Myocardial Dysfunction via Activation of Grk3 and Phosphorylation of Erk
Objective: To investigate the signaling pathway of kappa opioid receptor (κ-OR) on postresuscitation myocardial protection.
Method: A total of 120 male SD rats were randomized into control group (n=40), κ-OR agonist group (n=40) and κ-OR inhibitor group (n=40). Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. Cardiac arrest was started when systolic blood pressure dropped below 25mmHg. CPR with chest compression and mechanical ventilation were started 6mins after cardiac arrest. Normal saline (1ml/kg), U50488H (ΚOR agonist, 1mg/kg) or GNTI(ΚOR inhibitor, 0.5mg/kg) was injected from on set of CPR in each group. The baseline blood gas, HR, SBP, DBP, MAP, dP/dtmax and -dP/dtmax were measured. The rat hearts were harvested at 1h, 2h, 6h, 12h and 24h post resuscitation (PR). The expression of both total κ-OR and phosphorylated κ-OR in myocaridum were determined, the likely signaling pathway molecules of G protein receptor kinase 3(GRK3) and ERK1/2 were detected.
Results: The postresuscitation myocardial function, include HR, SAP, MAP, dP/dtmax and -dP/dtmax were improved in κ-OR agonist group compared to κ-OR inhibitor and control group, specifically after PR2h(p<0.01).Both phosphorylated κ-OR and GRK3 protein impression were significantly increased in κ-OR agonist group, in comparison to κ-OR inhibitor group and control group (p<0.01). Positive linear correlation was observed between κ-OR and GRK3. The ERK1/2 mRNA and protein expression were significantly increased in κ-OR agonist group and significantly decreased in κ-OR inhibitor group, in comparison to control group(p<0.05).
Conclusion: The activation of κ-OR improves postresuscitation myocardial dysfunction. The protective effects of κ-OR may via activation of GRK3 and ERK1/2 signaling pathway.
Author Disclosures: Y. Shan: None. J. Wan: None. Z. Lin: None. J. Zheng: None. Z. Huang: None.
- © 2015 by American Heart Association, Inc.