Investigate The Effection Of Remifentanil On Sinoatrial Node Autorhythmicity Of Rabbit

Remifentanil is a new μ-agonist opioid drug that undergo widespread extrahepaticmetabolism by plasma and tissue non-specific esterases was used in clinical in1995,with the desirable characteristic of rapid onset/offset action,which makes itrecommendable for controlling the cardiovascular response to surgicalstimulation.Nevertheless,more reports have demonstrated that remifentaniladministration could be associated with arterial hypotension and bradycardia inclinical practice.So far, the mechanism of remifentanil causes bradycardia is controversial intheory.Opioid-related bradyarrhythmias are currently attributed to a transientprevalence of parasympathetic tone over the sympathetic one,but other studies showsthese negative chronotropic effects are not exclusively due to an increasedparasympathetic activity,this drug may exerts a direct negative chronotropic action onsinoatrial node.Objective:To investigate the effects of remifentanil on sinoatrial node autorhythmicity inrabbits,then explore whether the drug have a direct effection on the sinus node cellscauses bradycardia and discuss the mechanism for it.The results can provides basistheory to explain the clinical phenomenon of bradycardia induced by the drug.Methods:Conventional microelectrode technique is using in the project to record the effectionof remifentanil on the spontaneous action potential of rabbit sinus node cells andobserve the concentration-dependent manner.After this,Ca²⁺channel agonist BayK8644and K⁺channel blocker TEA will be given,then observe the action potentialchanges. Based on above results can judge the relations between the channels and theeffection of remifentanil.Results:1.Remifentanil （2-8ng/ml） progressively decreased the amplitude of actionpotential（APA）,rate of pacemaker firing（RPF）,velocity of diastolicdepolarization（VDD） and prolonged the action potential duration at90%repolarization（APD90） in a concentration dependent manner.At8ng/ml concentration,APA decreased from70.6±3.0mV to60.6±2.8mV（P<0.01）,VDD and RPF decreased from65.0±4.0mV/s and122.4±12.7beats/min to34.5±4.2mV/s and101.4±11.2beats/min（P<0.01）,respectively. APD90prolonged from137.1±7.3ms to152.3±5.9ms（P<0.01）.Given remifentanil at16ng/ml and32ng/mlconcentration, the action potential parameters did not change.2.The sinoatrial node was exposed to remifentanil16ng/ml for15min, APA decreasedfrom69.9±2.4mV to60.5±2.2mV（P<0.01）, VDD and RPF decreased from64.5±3.5mV/s and122.6±9.8beats/min to34.6±2.9mV/s and101.8±9.6beats/min（P<0.01）, respectively. APD90prolonged from137.9±7.4ms to152.4±5.9ms（P<0.01）. Pretreatment with Bay K8644（16ng/ml） could block theeffects of remifentanil on SA node pacemaker cells.3.The sinoatrial node was exposed to remifentanil16ng/ml for15min, APA decreased from67.5±2.2mV to61.8±2.8mV （P<0.01）, VDD and RPF decreased from60.0±2.0mV/s and119.3±6.6beats/min to35.0±2.9mV/s and99.6±5.8beats/min（P<0.01）, respectively. APD90prolonged from133.0±3.3ms to148.8±5.3ms（P<0.01）. Pretreatment with TEA（20nmol/L） did not affect theelectrophysiologic effects of remifentanil on SA node pacemaker cells.Conclusion:Remifentanil exerts a negative chronotropic action on SA node pacemaker cells ofrabbit.These effects are likely due to decrease Ca²⁺current,opening K⁺channelsunlikely play a major role in these effects.