Effect of reperfusion strategy on QT dispersion in patients with acute myocardial infarction:Impact on in-hospital arrhythmia

BACKGROUND Myocardial ischemia and ST-elevation myocardial infarction(STEMI)increase QT dispersion(QTD)and corrected QT dispersion(QTcD),and are also associated with ventricular arrhythmia.AIM To evaluate the effects of reperfusion strategy[primary percutaneous coronary intervention(PPCI)or fibrinolytic therapy]on QTD and QTcD in STEMI patients and assess the impact of the chosen strategy on the occurrence of in-hospital arrhythmia.METHODS This prospective,observational,multicenter study included 240 patients admitted with STEMI who were treated with either PPCI(group I)or fibrinolytic therapy(group II).QTD and QTcD were measured on admission and 24 hr after reperfusion,and patients were observed to detect in-hospital arrhythmia.RESULTS There were significant reductions in QTD and QTcD from admission to 24 hr in both group I and group II patients.QTD and QTcD were found to be shorter in group I patients at 24 hr than those in group II(53±19 msec vs 60±18 msec,P=0.005 and 60±21 msec vs 69+22 msec,P=0.003,respectively).The occurrence of in-hospital arrhythmia was significantly more frequent in group II than in group I(25 patients,20.8%vs 8 patients,6.7%,P=0.001).Furthermore,QTD and QTcD were higher in patients with in-hospital arrhythmia than those without(P=0.001 and P=0.02,respectively).CONCLUSION In STEMI patients,PPCI and fibrinolytic therapy effectively reduced QTD and QTcD,with a higher observed reduction using PPCI.PPCI was associated with a lower incidence of in-hospital arrhythmia than fibrinolytic therapy.In addition,QTD and QTcD were shorter in patients not experiencing in-hospital arrhythmia than those with arrhythmia.

Effects of Potassium Aspartate and Magnesium on Ventricular Arrhythmia in Ischemia-reperfusion Rabbit Heart

The aim of this study was to determine if the potassium aspartate and magnesium （PAM） prevent reperfusion-induced ventricular arrhythmias （RIVA） in ischemia-reperfusion （IR） rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode＇s solution, and in ischemia group and PAM groups the perfusion of Tyrode＇s solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode＇s solution and the PAM group with Tyrode＇s solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion （TDR） and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group （P〈0.05）. The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group （P〈0.05）. Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.

Prophylactic effect of magnesium sulfate against reperfusion induced arrhythmias in the isolated rat hearts

Prophylactic effect of magnesium sulfate on reperfusion arrhythmias was studiedusing a left anterior descending coronary artery occlusion followed by reperfusion in theisolated rat heart.In the first studies,we have observed a bell-shaped relationship be-tween the incidence of reperfusion-induced ventricular fibrillation（VF）and the durationof preceding ischemia.With 5,10,15,20 and 25 min of ischemia,10,70,60,50 and 20per cent of the hearts exhibited irreversible VF,respectively.In the second studies（10 minischemia）,perfusate magnesium sulfate was increased to 3.6,4.8 and 6.0 mmol/L 1 min be-fore coronary ligation,VF fell in a dose-dependent manner from its control total inci-dence of 100%（1.2mmol/L MgSO4）to 82%,73% and 18%（P【0.01）,respectively.Heartrate was also reduced in a dose-dependent manner,falling from its control value of326±11 to 227±22 beats/min with the highest concentration of magnesium sulfate.Asperfusate magnesium sulfate was increased to 6.0 mmol/L just before reperfusion,no an-ti-arrhythmic effects were observed.With an anti-arrhythmic concentration of magnesiumsulfate（6.0 mmol/L,increased 1 min before ligation）,calcium concentration was increasedby 1.5 mmol/L at the same time,under these conditions the anti-arrhythmic effect of mag-nesium sulfate was lost and its negative chronotropic effect was also partially abolished.We conclude that magnesium sulfate has a certain prophylactic effect againstreperfusion induced arrhythmias and this could be due to a direct or indirect calci-um-antagonist action.

Effect of berberine on reperfusion arrhythmias in the isolated rat heart

Effect of berberine on reperfusion arrhythmias was studied using a10min left anterior descending coronary artery occlusion followed by reperfusionin the isolated rat heart.Berberine when given 10min before coronary ligation re-duced the incidence of reperfusion arrhythmias in a dose-dependent manner.With10-5,3.16×10-5 and 10-4mol/L of berberine,ventricular fibrillation was reducedfrom its control incidence of 100% to 90%,70% and 40% （P【0.05） respectively.Heart rate was also reduced in a dose-dependent manner,falling from its controlvalue of 282±11 to 180±11 beats/min with the highest concentration of berberine.Coronary flow was increased in all berberine treated groups.With anantiarrhythmic dose of berberine (10-4mol/L),hearts were paced （5 Hz） duringischemia period;under these conditions the anti-arrhythmic effect of berberinewas lost.When berberine (3.16×10-5 and 10-4mol/L) was administered just beforereperfusion,no anti-arrhythmic effects were observed.The α-adrenoceptor antago-nist phentolamine (2.6×10-5mol/L) prevented reperfusion arrhythmias and ismuch more effective than berberine.These results suggest that the prophylatic ef-fects of berberine on reperfusion arrhythmias in the isolated rat heart are due toits negative chronotropic properties.

Activation of epidermal growth factor receptor mediates myocardial ischemia/reperfusion arrhythmias in anaesthetized rats

Objectives Epidermal growth factor receptor （EGFR）is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart.The present study was designed to investigate whether EGFR activation would mediate myocardial arrhythmias induced by ischemia/reperfu- sion in anaesthetized rats.Methods and results Myocardial ischemia/reperfusion arrhythmias were induced by 10 min ligation of the left anterior descending coronary artery,followed by a 30 min reperfusion in anaesthetized rats.Incidence and severity of cardiac arrhythmias were significantly reduced by pretreatment with the EGFR kinase inhibitor AG556.Phosphorylation level of myocardial EGFR was increased during ischemia and at early reperfusion.Intramyocardial transfection of EGFR siRNA reduced EGFR mRNA and protein,and decreased the incidence of ventricular fibrillation induced by reperfusion.Interestingly,tyrosine phosphorylation levels of cardiac Na+ channel(INa) and L-type Ca2+ channel(ICa.l) were significantly increased at corresponding time points to the alteration of phosphorylated EGFR level during reperfusion.AG556 pretreatment countered the increased tyrosine phosphorylation level of Na+ and L-type Ca2+ channels induced by reperfusion.No significant alteration was observed in tyrosine phosphorylation levels of cardiac Kv4.2 and Kir2.1 channels during the cardiac ischemia/reperfusion. Conclusions These results demonstrate for the first time that EGFR plays an important role in the genesis of myocardial ischemia/reperfusion arrhythmias,which is likely mediated at least in part by enhancing tyrosine phosphorylation of cardiac Na+ and L-type Ca2+ channels.

Effect of electroacupuncture at Neiguan(PC6)at different time points on myocardial ischemia reperfusion arrhythmia in rats

OBJECTIVE:To observe the effects of electroacupuncture at Neiguan(PC6)at different time points on reperfusion arrhythmia(RA)after myocardial ischemia and reperfusion in rats,and to investigate the correlation of this protective effect with nerve growth factor(NGF),tyrosine kinase A(Trk A),tyrosine hydroxylase(TH),and norepinephrine(NE).METHODS:A total of 72 Sprague-Dawley male rats were randomly divided into six groups(n=12 rats/group):normal group(Norm),sham operation group(Sham),ischemia reperfusion group(I/R),pre-ischemic electroacupuncture group(EAI),pre-reperfusion electroacupuncture group(EAII),post-reperfusion electroacupuncture group(EAIII).The myocardial ischemia-reperfusion injury(MIRI)model was induced by occlusion of left anterior descending coronary artery for 20 min followed by reperfusion for 40 min in rats.With no intervention in the Norm group and only threading without ligation in the Sham group.Electroacupuncture pretreatment at 20 min/d for 7 d before ligation in the EAⅠgroup,20 min of electroacupuncture before reperfusion in the EAII group and 20 min of electroacupuncture after reperfusion in the EAIII group.The electrocardiogram(ECG)of each group was recorded throughout the whole process,and the success of the MIRI model was determined based on the changs of J-point and T-wave in the ECG.The arrhythmia score was used to record premature ventricular contractions,ventricular tachycardia and ventricular fibrillation during the reperfusion period to assess the reperfusion induced arrhythmias.The expression levels of NGF,Trk A,TH protein were measured by Western blot.Moreover,the expression levels of plasma and myocardial NE levels were detected by enzyme linked immunosorbent assay.RESULTS:The differences between Norm group and Sham group were not statistically significant in all indexes.Arrhythmia score,myocardial NGF,Trk A,TH,and NE expression were significantly higher in the I/R group compared with the Sham group.Arrhythmia score,myocardial NGF,Trk A,TH,and NE expression were significantly lower in each EA group compared with the I/R group.CONCLUSION:Electroacupuncture at Neiguan(PC6)at different time points can reduce the incidence and severity of reperfusion arrhythmias in rats.This protective effect is related to electroacupuncture regulating NGF,Trk A,TH,NE expression and reducing sympathetic hyperactivation.

吡格列酮经Ras依赖性途径保护缺血再灌注心肌细胞的实验研究

目的观察吡格列酮对缺血再灌注损伤心肌细胞的保护作用,并探讨其与Ras信号转导通路的关系。方法体外培养乳鼠心肌细胞,分正常对照组(Co组)、缺血再灌注组(I/R组)、吡格列酮预处理组(Pi组)、Ras抑制剂Manumycin组(Ma组)。采用MTT分析法测定各组心肌细胞活性;测定各组MDA、SOD、LDH、ATP含量。比较组间差异。结果与Co组比较,I/R组心肌细胞活性、SOD、ATP含量降低,MDA、LDH含量增加,差异有统计学意义(P<0.01);与I/R组比较,Pi组心肌细胞活性、SOD、ATP含量增加,MDA、LDH含量降低,差异有统计学意义(P<0.01);与Pi组比较,Ma组心肌细胞活性、SOD、ATP含量降低,MDA、LDH含量增加,差异有统计学意义(P<0.01)。结论吡格列酮预处理可减轻缺血再灌注心肌细胞损伤,保护机制与Ras信号转导通路有关。

调心安神针法对缺血再灌注心律失常大鼠心肌组织微小RNA的影响

目的观察调心安神针法对缺血再灌注心律失常(RA)大鼠心肌组织微小RNA(miRNA1、miRNA133a)表达的影响以了解调心安神针法治疗缺血再灌注心律失常的作用机制。方法40只大鼠随机分为假手术组、模型组、针刺组及胺碘酮组,针刺组施以调心安神针刺法预处理7 d(取穴:灵台、神道、双侧内关、百会)。采用结扎/松解左冠状动脉前降支的方法制作RA模型大鼠。造模完毕后,酶联免疫法检测血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)含量,苏木精-伊红染色观察心肌组织,RT-PCR法检测缺血区中央部位心内膜心肌miRNA1、miRNA133a的表达水平。结果针刺组、胺碘酮组CK-MB和LDH的含量较模型组明显降低(P<0.01)。针刺组、胺碘酮组miRNA1表达均较模型组明显降低(P<0.01),且胺碘酮组低于针刺组(P<0.01);针刺组和胺碘酮组miRNA133a表达均较模型组明显增加(P<0.05),针刺组与胺磺酮组差异无统计学意义(P>0.05)。结论调心安神针法预处理和注射胺碘酮均能改善心肌损伤,减少心律失常的发生,其机制可能与通过下调缺血再灌注心律失常大鼠心肌组织miRNA1表达,上调miRNA133a的表达有关。

全身免疫炎症指数与急性心肌梗死患者再灌注后发生室性心律失常的关联性分析

目的 评估全身免疫炎症指数(systemic immune-inflammation index,SII)与急性心肌梗死(acute myocardial infarction,AMI)患者再灌注治疗后室性心律失常(VA)发生风险间的关联性。方法 连续选取2023年1月至2024年4月就诊于新疆维吾尔自治区人民医院确诊为AMI并接受经皮冠状动脉介入术(PCI)的患者共计815例。根据SII中位数水平将患者分为低SII组(n=349)和高SII组(n=350)两组;结局指标为术后发生VA。采用logistic回归分析评估SII与AMI患者术后VA的关联,应用限制性立方样条图(RCS)评估二者间的剂量-反应关系,ROC曲线分析SII对术后VA发生事件的预测能力,同时进行亚组分析检验结果的稳健性。结果 在最终纳入的699例患者中,193例(27.6%)患者出现VA。校正潜在混杂因素后,SII每增加一个标准差,AMI患者的VA发生风险增加0.72倍(OR=1.72,95%CI 1.32~2.24,P<0.001);与低SII组相比,高SII组AMI患者的VA发生风险增加1.42倍(OR=2.42,95%CI 1.44~4.07,P=0.001)。多变量校正限制性立方样条图(RCS)显示,SII与AMI患者再灌注后发生风险之间存在线性剂量-反应关系(非线性P值=0.056)。ROC曲线分析,SII预测AMI患者PCI后VA的曲线下面积(AUC)为0.749(95%CI 0.704~0.795),敏感度70.9%,特异度71.5%。亚组分析提示,与<60岁、女性患者相比,高SII水平与≥60岁的男性AMI患者PCI术后VA发生风险的关联更强。结论 SII升高与AMI患者再灌注后室性心律失常发生风险增加存在明显相关性,且随着SII水平升高,VA发生风险逐步增加。

基于网络药理学及计算机辅助药物设计方法分析雷诺嗪治疗心肌缺血再灌注损伤致心律失常的潜在靶点及机制

目的利用网络药理学方法和计算机辅助药物设计策略,分析雷诺嗪对心肌缺血再灌注损伤(MIRI)致心律失常的潜在治疗靶点及机制。方法采用Swiss Target Prediction数据库和DrugBank数据库预测雷诺嗪潜在的作用靶点。采用GeneCards数据库搜集MIRI和心律失常疾病的靶点,检索时间为建库至2023年1月26日,将雷诺嗪、MIRI和心律失常相关靶点进行交集比对以获取雷诺嗪治疗MIRI致心律失常的关键靶点。利用STRING数据库和Cytoscape软件绘制靶点蛋白互相作用网络。利用DAVID数据库对靶点进行信号通路富集分析。利用Cy-toscape软件构建药物-靶点-信号通路网络。利用分子对接软件验证雷诺嗪与交集靶点结合能力。最后通过分子相似性分析及分子动力学模拟研究,验证预测靶点的准确性。结果筛选获得雷诺嗪治疗MIRI致心律失常的潜在作用靶点30个。通过蛋白互相作用分析共获得8个核心靶点,包括SRC、PIK3CA、MAPK8、MAPK14、JAK1、MAP2K1、JAK2和PIK3CG。GO生物分析共筛选出177个生物学过程,其中包括123个细胞生物过程,23个细胞组成和31个分子功能。KEGG分析发现119条相关信号通路。分子对接分析结果显示,雷诺嗪与8个核心靶蛋白均具有较好的亲和力。分子相似性分析结果显示,雷诺嗪与8个核心靶蛋白原配体都存在一定相似性。分子动力学模拟了相关性最高的3个靶点(SCR、PIK3CA和MAPK8),结果显示雷诺嗪表现出MAPK8和SCR抑制剂潜力,而对PIK3CA的抑制剂位点结合潜力相对较差,结合文献复习,推测出雷诺嗪对MIRI致心律失常治疗作用的最相关分子机制。结论雷诺嗪可通过多靶点、多途径治疗MIRI致心律失常,这对促进治疗MIRI致心律失常靶向药物的研发及临床应用具有重要意义。

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury

Background:Dysfunction of the gap junction channel protein connexin 43(Cx43)contributes to myocardial ischemia/reperfusion(I/R)-induced ventricular arrhythmias.Cx43 can be regulated by small ubiquitin-like modifier(SUMO)modification.Protein inhibitor of activated STAT Y(PIASy)is an E3 SUMO ligase for its target proteins.However,whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.Methods:Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid(shRNA)using recombinant adeno-associated virus subtype 9(rAAV9).Two weeks later,the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion.Electrocardiogram was recorded to assess arrhythmias.Rat ventricular tissues were collected for molecular biological measurements.Results:Following 45 min of ischemia,QRS duration and QTc intervals statistically significantly increased,but these values decreased after transfecting PIASy shRNA.PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R,as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation,and reduced arrythmia score.In addition,myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation,accompanied by reduced Cx43 phosphorylation and plakophilin 2(PKP2)expression.Moreover,PIASy downregulation remarkably reduced Cx43 SUMOylation,accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.Conclusion:PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression,thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

冠心舒通胶囊联合单硝酸异山梨酯预防急性心肌梗死患者PCI术后再灌注心律失常的效果

目的:观察冠心舒通胶囊联合单硝酸异山梨酯预防急性心肌梗死(AMI)患者经皮冠状动脉介入治疗(PCI)术后再灌注心律失常(RA)的效果。方法:选取2020年9月至2022年9月该院收治的86例行PCI术的AMI患者进行前瞻性研究,按随机数字表法将其分为对照组与研究组各43例。对照组采用单硝酸异山梨酯片治疗,研究组在对照组基础上联合冠心舒通胶囊治疗。比较两组治疗前后心肌损伤标志物[肌酸激酶同工酶(CK-MB)、N端脑钠肽前体(NT-proBNP)、肌钙蛋白I(cTnI)]水平、炎性指标[白细胞介素-6(IL-6)、超敏C反应蛋白(hs-CRP)、半乳糖凝集素-3(Gal-3)]水平、RA发生率和不良反应发生率。结果:治疗后,两组CK-MB、NT-proBNP、cTnI水平均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05);两组IL-6、hs-CRP、Gal-3水平均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05);研究组RA发生率低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:冠心舒通胶囊联合单硝酸异山梨酯应用于PCI术后AMI患者可降低心肌损伤标志物水平、炎性指标水平和RA发生率,其效果优于单纯单硝酸异山梨酯片治疗。

急性心肌梗死患者急诊介入术后发生再灌注心律失常的危险因素分析

目的分析急性心肌梗死(AMI)患者急诊介入术后发生再灌注心律失常的危险因素。方法统计108例AMI患者急诊介入术后再灌注心律失常发生情况,探讨术后发生再灌注心律失常的危险因素。结果108例AMI患者急诊介入术后再灌注心律失常发生率为43.52%。单因素和Logistics回归分析显示,Killip分级Ⅲ级、下壁梗死、病变血管血流TIMI分级0级、发病6h内进行介入术治疗是急诊介入术后发生再灌注心律失常的危险因素(P<0.05)。结论AMI患者急诊介入术后发生再灌注心律失常的风险较高,其危险因素包括Killip分级Ⅲ级、下壁梗死、病变血管血流TIMI分级0级、发病6 h内进行介入术治疗。

急性心梗行直接冠脉介入术中再灌注性心律失常的临床特点及预后的影响

目的探讨急性心梗患者行直接冠脉介入术中再灌注性心律失常的临床特点及对预后的影响。方法选取2023年1月至2024年1月期间在高阳县医院接受直接冠脉介入术治疗的40例急性心梗患者,记录术中再灌注性心律失常发生情况,分析其临床特点,观察再灌注性心律失常对患者预后的影响。结果40例患者中,15例在术中出现再灌注性心律失常,最常见的类型为室性早搏,共10例;其次为室性心动过速,共3例;较少见的为心室颤动,共2例;再灌注性心律失常主要发生在直接冠脉介入术中血管再通后的5~30 min内。患者年龄、性别、病变部位等因素与再灌注性心律失常的发生均具有一定的相关性。在预后方面,发生再灌注性心律失常的患者在短期和长期内均表现出心功能恢复较差、并发症发生率较高的特点。结论急性心梗患者行直接冠脉介入术中再灌注性心律失常的发生具有一定的临床特点,对患者预后具有显著影响。临床应加强对再灌注性心律失常的监测和干预,以改善患者预后。

定心方对家兔心肌缺血及再灌注损伤的保护作用和抗心律失常作用的研究

目的:研究定心方(DXR)抗兔心肌缺血及再灌注损伤和抗心律失常作用。方法:兔冠状动脉双重结扎造成心肌梗塞,观察各组心律失常情况并检测血浆超氧化物歧化酶(SOD)、cAMP、去甲肾上腺素(NE)、多巴胺(DA)、5羟色胺(5HT),观察心肌超微结构。结果:DXR对兔心肌梗塞后心律失常有拮抗作用,其中DXR大剂量组与对照组比较有显著性差异(P<001);对缺血再灌注心律失常也有拮抗作用,DXR大、小剂量组与对照组比较均有显著性差异(P<001);对上述状态的心电图ST-T抬高有改善作用。实验表明,DXR能升高血清SOD浓度,而使cAMP、NE、DA、5HT浓度和全血粘度降低。结论:DXR能拮抗心肌缺血及再灌注损伤和心律失常,其机理可能通过清除氧自由基、调节细胞第二信使、抑制交感神经系统、改善局部循环,保护线粒体、抑制溶酶体活化使心肌细胞免受损伤而实现。

尼可地尔对老年急性ST段抬高型心肌梗死患者介入术后心功能的影响

目的观察尼可地尔对老年急性ST段抬高型心肌梗死(STEMI)患者直接PCI后心功能的影响。方法将接受直接PCI的STEMI患者100例随机分为尼可地尔组49例和对照组51例。观察2组PCI术后心肌血流灌注指标,评价住院期间及随访6个月心功能。结果与对照组比较,尼可地尔组PCI术后TIMI 3级血流(93.9%vs80.4%)、肌酸激酶同工酶(CK-MB)达峰时间<14h(87.8%vs 70.6%)及ST段回落(85.7%vs 68.6%)显著升高,再灌注心律失常比例(40.8%vs 60.8%)、校正TIMI帧计数及CK-MB峰值降低(P<0.05,P<0.01)。尼可地尔组随访6个月B型钠尿肽(BNP)、左心室舒张末期容积指数(LVEDVI)、左心室收缩末期容积指数(LVESVI)低于对照组,LVEF高于对照组(P<0.05,P<0.01)。与住院期间比较,对照组随访6个月BNP、LVEDVI、LVESVI升高(P<0.05);尼可地尔组BNP降低、LVEF升高(P<0.05)。对照组随访6个月MACE发生率高于尼可地尔组(47.1%vs 26.5%,P=0.034)。结论尼可地尔改善老年STEMI患者直接PCI术后心功能。

U50,488H抗大鼠缺血/再灌注损伤心律失常作用与抑制钠通道电流有关

目的观察κ阿片受体选择性激动剂(U50,488H)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)室性心律失常的影响并探讨其可能的机制。方法观察U50,488H对大鼠I/R整体动物模型血浆肌酸磷酸激酶(CK)、乳酸脱氢酶(LDH)水平的影响;分离正常大鼠心脏,采用Langen-dorff离体心脏灌流方法,预先给予U50,488H(5mmol·L-1)和NE(100μmol·L-1),测定其对血流动力学指标和对心律失常的影响;常规酶解法分离成年大鼠心室肌细胞,采用全细胞膜片钳技术观察U50,488H对钠电流的作用。结果①U50+I/R组血浆中CK和LDH的含量较I/R组明显降低(P<0.01)。②与I/R组相比,给予U50,488H后,心率明显下降(P<0.05)。③对照组偶发早搏,I/R组心律失常发生频率明显增加,与I/R组相比较,I/R+NE组心律失常评分明显增高(P<0.01);如果提前给予U50,488H,发现不仅可以明显降低I/R组缺血和再灌注期间室速和室颤的发生率(P<0.01)及降低I/R组心律失常的评分,而且明显降低I/R+NE组心律失常的评分(P<0.01)。④U50,488H(100μmol·L-1)可以明显降低心室肌细胞的钠电流(P<0.01)。结论κ阿片受体激动剂U50,488H对I/R时的心律失常有拮抗作用,其作用可能是通过抑制心肌细胞的钠电流而实现的。

交感神经活动影响再灌注心律失常

目的：观察交感神经活动对再灌注心律失常（ＲＡ）的影响。方法：采用猫在体心肌缺血－再灌注动物模型，同步记录再灌注期肾交感神经放电活动积分值（ＩＲＳＮＡ）和ＲＡ。结果：（１）ＩＲＳＮＡ的增加和ＲＡ发生分别出现在再灌注期的第１～２秒和第４秒。ＲＡ紧随ＩＲＳＮＡ的增加而出现，至再灌注期的第１０～１５秒，ＩＲＳＮＡ的增加达峰值，ＲＡ表现为室性纤维颤动（ＶＦ）；（２）发生ＶＦ组ＩＲＳＮＡ的增加值显著大于发生室性心动过速（ＶＴ）组和室性早搏（ＶＰＢ）组（Ｐ＜０．００１）；ＶＴ组ＩＲＳＮＡ的增加值亦明显大于ＶＰＢ组（Ｐ＜０．０５）。结论：ＲＡ的发生不仅与交感神经活动增强的时相一致，而且其严重程度还与交感神经活动增强程度正相关，提示交感神经活动能促进ＲＡ的发生。

川芎嗪对大鼠缺血再灌注性心律失常的预防作用

以SD大鼠制成心肌缺血再灌注模型．研究川芎嗪对心肌缺血再灌注性心律失常的防治作用，结果表明：与对照组相比．川芎嗪组再灌注心律失常发生率明显减少（分别为88．88％和11．11％，P＜0．01）．再灌注性心律失常持续时间明显缩短（分别为55．88±23．98s和2．55±0．45S．P＜0．01）。结果提示川芎嗪对大鼠心肌缺血再灌注性心律失常具有良好的防治作用。