Effects Of ?-adrenoceptor Agonists On Bupivacaine-induced Cardiotoxicity

Part one Effects of ?-adrenoceptor agonists on the electrocardiogram of bupivacaine-induced on myocardialObjective: Epinephrine is a first-line reagent for treating cardiac arrest because it increases diastolic pressure and coronary perfusion pressure.However,patients who have undergone bupivacaine-induced cardiac arrest are often resistant to adrenergic therapy and can develop severe pulmonary edema after receiving epinephrine.Our previous work has shown that isoprenaline aggravated bupivacaine-induced cardiamyocyte contractile depression,and esmolol inhibited the aggravation.In this work we tested the effect of ?-adrenoceptor agonists on the electrocardiogram of bupivacaine in intoxicated rats.Methods:Animal modelAdult SD rats,male(body weight,200~250 g),were anesthetized with 10% chloral hydrate(0.3ml/100g)by intraperitoneal injection.After the puncture of caudal vein for administration of drug,body surface electrocardiograms(ECGs)were obtained with rats in the supine position.ECGs were recorded using three needle electrodes placed subcutaneously: red on left lower extremity,green on right upperextremity and black on right lower extremity.The distal portions of the leads were secured in positions that approximated those of the lead II of a standard ECG.All rats breathed spontaneously throughout this procedure.We use a RM6240 C Multi-channel physiological signal acquisition and processing system(Chengdu instrumentCo.,Chengdu,China)to perfrom the ECGs on monitor.GroupingThe rats were randomly divided into 3 groups: bupivaca ine+saline group,bupivacaine+isoprenaline group,bupivacaine+epinephrine group.Every group had 7 rats.Administration of drugBupivacaine was intravenous infused at 0.75mg/kg/min for 12 minutes and 40 seconds.Then 0.4ml of saline(Bupivacaine+saline group),or 0.08mg/kg of isoprenaline in 0.4ml saline(Bupivacaine+isoprenaline group),or 6?g/kg of epinephrine(Bupivacaine+epinephrine group)was intravenously injected as a bolus.Measurement protocolDuring the infusion,electrocardiogram was continually monitored using a RM6240 C Multi-channel physiological signal acquisition and processing system.Analyze and record the duration of PR,QRS,heart rate.Results:1Bupivacaine significantly depresseed myocardial conduction.Bupivacaine prolonged the duration of PR and QRS,but reduced heart rate(P<0.05).2 Isoprenaline(0.08mg/kg)and epinephrine(6?g/kg)had no effect on the duration of PR and QRS.Isoprenaline and epinephrine could increase heart rate after administration for 1 minutes(P<0.05).However,they had no difference from time on.Part two ?-adrenoceptor agonists aggravate the depressed left ventricular function of bupivacaine-inducedObjective: Bupivacaine-induced cardiac toxicity is rare but always life threatens.Adrenoceptor agonists are the first-line drugs for treating cardiac arrest.But patients who have undergone bupivacaine induced cardiac arrest are often resistant to adrenergic therapy.By using a video-based edge-detection system we have found that bupivacaine induced depression of myocardial contractility in isolated rat cardiomyocytes.Isoprenaline can enhance the inhibition of myocardial contractility,and esmolol can reverse the effect of isoprenaline.Here,we tested the effect of epinephrine and isopesnaline on bupivacaine-induced cardiac contractile depression in anesthetized rats.Methods:Animal modelAdult SD rats,male(body weight,200~250g),were anesthetized with 10% chloral hydrate(0.3ml/100g)and fixed in the supine position.After the puncture of caudal vein for administration of drug,the cardiac cather technique was used through carotid artery to meassure the changes of left venticular pressure.Ventricular pressure waveform was monitored and recorded by RM6240 C Multi-channel physiological signal acquisition and processing system(Chengdu instrument Co.,Chengdu,China).GroupingThe rats were randomly divided into 3 groups: bupivacaine+saline group,bupivacaine+isoprenaline group,bupivacaine+epinephrine group.Every group had 7 rats.Administration of drugBupivacaine was intravenously infused at 0.75mg/kg/min for 12 minutes and 40 seconds.Then 0.4ml of saline(Bupivacaine+saline group),or 0.08mg/kg of isoprenaline in 0.4ml saline(Bupivacaine+isoproterenol group),or 3?g/kg of epinephrine in 0.4ml of saline(Bupivacaine+epinephrine group)was intravenously injected.Measurement protocolLeft ventricular hemodynamic variables was continually recorded as described above.Results:1 Bupivacaine depressed cardiac function.LVSP?+dp/dt max and-dp/dt max was significantly reduced,but LVEDP was increased significantly(P<0.05).2 Isoprenaline and epinephrine worsened the cardiac function induced by bupivacaine.Isoprenaline or epinephrine induced a further reduction in LVSP and +dp/dt max(P<0.05).Conclusions:1 Bupivacaine can suppress myocardial conduction and left ventricular function in rats.2 ?-adrenoceptor agonists can significantly aggravate bupivacaine induced cardiotoxicity in rats.?-adrenoceptor agonists have no effect on bupivacaine-induced cardiotoxicity in rats.However,they can improve the myocardial automaticity bupivacaine-induced.