| Cardiovascular disease is a leading cause of worldwide death in both menand women.Among the manifestations of cardiovascular disease, a significantcause of mortality is sudden cardiac death resulting from malignant ventriculararrhythmia.coronary atherosclerosic heart disease is the most common clinicaltype of cardiovascular disease,the main pathology is the acute myocardialischemia/reperfusion injury.The various types of clinical myocardial ischemiacan cause arrhythmia,of which the most common was ventriculararrhythmia,therefore, the prevention and treatment of ischemic ventriculararrhythmia is one of the important means to reduce the mortality ofcardiovascular disease.Studies have shown that Dexmedetomidine is a newtype of high efficiency, high selectivity of α2adrenergic agonists, with sedation,analgesia,and so on,and also can reduce the sympathetic nervous tension,catecholamine release,the release of inflammatory mediators,meanwhile,italso can enhance the vagus nerve activity,reduce the generation of myocardialcyclic adenosine monophosphate (cAMP) and L-type calcium channel.consequently,extending the myocardial repolarization and effective refractoryperiod,thus reduce the supraventricular tachycardia. Mitochondrial sensitivepotassium channels (mito-KATP) plays an important role in myocardialischemia-reperfusion injury, after opening mitochondria sensitive potassiumchannels can promote CX43protein phosphorylation. Studies have shown thatCX43protein have a close relationship with the incidence of arrhythmia.Theeffect of DEX on ischemia/reperfusion-induced arrhythmia，however，has notbeen reported yet.Objective: The aim of present study was to explore the effect of DEX onarrhythmia induced by ischemia/reperfusion in rat and the underlying mechanism.Methods: Thirty six male adult Sprague-Dawley rats (body weight270-320g) were randomly divided into six groups: ischemia/reperfusion group(I/R)、 Dexmedetomidine group （DEX）、 Yohimbine group （YOH）、5-Hydroxydecanoic acid sodium salt group（5-HD）、Dexmedetomidine+Yoh-imbine group（DEX+YOH）and Dexmedetomidine+5-Hydroxydecanoic acidsodium salt group (DEX+5-HD).The rats were anaesthetized and fixed inSupine position, the artery pressure wasmeasured through intubation in leftfemoral artery and ECG in standard lead II was recorded by Needle electrodewhich was inserted limbs subcutaneously.Then the heart of rats was treatedwith30min ischemia and120min reperfusion（I/R）through ligation of thecoronary artery, and artery blood pressure and lead II ECG were monitoredduring experiment continuously. The LVSP, LVDP and±dp/dtmax were alsorecorded by Power Lab system.The severity of the arrhythmia was evaluatedby arrhythmia score,after120min reperfusion,the expression of Cx43and itsphosphorylation protein (p-Cx43) were measured by western blotting.The ratsin I/R group experienced a30min ischemia and120min reperfusion,The ratsin DEX group were given a venous injection of dexmedetomidine beforeI/R,YOH group were given a venous injection of yohimbine beforeI/R,DEX+YOH group were given a venous injection of yohimbine,after5mingiven the dexmedetomidine befor I/R.5-HD group were given a venousinjection of5-HD befor I/R.DEX+5-HD group were given a venous injectionof5-HD,after5min given the dexmedetomidine befor I/R.Results:1Reperfusion of the ischemic myocardium can trigger the onset of variouscardiac arrhythmias include including,,premature ventricular beats、ventriculartachycardia and ventricular fibrillation.After the ligation of the coronary artery,The ischemic arrhythmia score in DEX rats was significantly less than that inI/R rats (P<0.05), the ischemic arrhythmia score of DEX+YOH andDEX+5-HD were significantly more than that in DEX rats (P<0.05);whilethere was no difference of the arrhythmia score between YOH and5-HD with I/R rats (P>0.05). Also, the reperfusion arrhythmia score in DEX rats wassignificantly less than that in I/R rats (P<0.05), and there was no difference ofthe arrhythmia score between YOH and5-HD with I/R rats during2hoursreperfusion (P>0.05);However,the ischemic arrhythmia score of DEX+YOHand DEX+5-HD were significantly more than that in DEX rats (P<0.05);2The blood pressure decreased in all rats,but the decrease in DEX groupwas significant less than that in I/R rats (P<0.05), while there was nodifference of the decrease between YOH and5-HD group with I/R rats(P>0.05),and the decrease in DEX+YOH and DEX+5-HD group wassignificant more than that in DEX rats (P<0.05);During reperfusion, therecovery of blood pressure in DEX rats was significantly high compared withthe I/R rats (P<0.05), while there was no difference of the recovery betweenYOH、5-HD with I/R rats (P>0.05),and the decrease in DEX+YOH andDEX+5-HD group was significant more than that in DEX rats (P<0.05);3The LVSP and±LVPdP/dt max were reduced during myocardialischemia. LVSP,+LVdP/dt max and-LVdP/dt max in I/R rats were decreasedsignificantly compared with the DEX group,the decrease in DEX+YOH andDEX+5-HD group was significant more than that in DEX rats (P<0.05),whilethere was no difference of the decrease between YOH and5-HD group withI/R rats (P>0.05);4Western blotting was observed following myocardial ischemia,our datawshowed that,the preservation of Cx43and p-Cx43protein in DEX rats wassignificantly high compared with the I/R rats (P<0.05),the rats treated withYOH and5-HD exhibited a marked reduction in the amount of phosphorylatedconnexin-43compared with the DEX rats (P<0.05), meanwhile the rats givenDEX+YOH and DEX+5-HD were significantly reduced in comparison withrats that underwent DEX(P<0.05).Summary:Dexmedetomidine can antagonize ischemia/reperfusion induc-ed arrhythmia and promote the recovery of artery blood pressure and thecardiac function, Its possible mechanisms may be related the effect of alpha2receptor which opened the mitochondrial ATP sensitive potassium channel and promoted myocardial Cx43protein phosphorylation. |
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