Endogenous Orphanin FQ Increases The Occurrence Of Ventricular Arrhythmia Caused By Acute Myocardial Ischemia In Rats

Background—Ventricular arrhythmia has became the primal reson for the people who die fromacute myocardial ischemia[1]. Orphanin FQ （OFQ nociceptin） whose structure primary is similarto dynorphin A indeed is a heptadecapeptide, but has low affinity binds to receptors of opioidclassical[2]. We had found that during acute myocardial ischemia there were more OFQ in pinalcords and dorsal root ganglion of rats [3], which suggest OFQ may participates in this process.Objective---We carried out this study to study the effects of endogenous OFQ on ventriculararrhythmia caused by acute myocardial ischemia in rats and explore the possible mechanism.Methods—The resuarch was devided into three experiments:1. In this experiment we use adult healthy male SD rats and the weigh of them were250-280g.They were divided into five groups randomly: U11,U9and U7groups were treatment with OFQantagonist compound UFP-101in the dosage of1×10^-11mol/kg,1×10^-9mol/kg and1×10^-7mol/kg, i.v. Calphostin C （0.1mg/kg） a specific inhibitor of PKC and UFP-101(1×10^-7)mol/kg was administered in U7-C group and the control group were treatment with saline5minbefore they were subjected to the coronary artery occlusion （CAO） for60min and ECG wereobserved and analyzed.2. We collected the ventricular myocytes from the heart of SD rats.The heart was perfusedwith an solution containing enzyme in Langendorff perfusion. Ventricular myocytes’ actionpotential （AP） was induced and recoded with the technique of whole-cell patch-clamp.Ventricular myocytes were perfused with The Tyrode’s solution contained OFQ in the dosage of1×10^-11mol/L,1×10^-9mol/L and1×10^-7mol/L, i.v.（O11,O9,O7; N=6）, UFP-101in the dosageof1×10^-8mol/L（U8; n=6） and OFQ (1×10^-9mol/L)+ufp-101(1×10^-8mol/L)（O9U8; N=6）.The effects of OFQ on Action potential duration （APD） were investigated.3. Study the role of PKC in the process of endogenous Orphanin FQ increases the occurrenceof ventricular arrhythmia caused by acute myocardial ischemia. Peptides were extracted fromthe heart which came from the experiment-1, a detection of PKC with no radioactive was used tomeasure the activity of PKC.Results—7Compared with C group Outbreak number of VEB （ventricular ectopic beats） werelower in U9and U7group P<0.05and can reduce the happening of ventricular tachycardia（VT）and ventricular fibrillation（VF） in U11,U9and U7group P<0.05. Cmopared with U7group theeffect that can drop the happening of ventricular arrhythmia was reversed in U7-C group. The time of ventricular arrhythmia distributed in U11, U9and U7groups was shortter than C group andU7-C groups and the difference mainly in the time of more than15min.8OFQshorted ratventricular myocytes’ APD in O11, O9and O7group obviously P<0.05and UFP-101canreversed the effect of OFQ.9Activity of PKC was higher in U11,U9and U7group comparedwith C group P<0.05.Conclusion—Endogenous OFQ increases the occurrence of ventricular arrhythmia cauced byCAO in rats which may result from inhibition of APD or PKC-dependent pathway.