硬膜外注射吗啡对兔急性缺血再灌注后左心功能的影响

目的在兔急性心梗再灌注模型中通过硬膜外给予吗啡,探讨其对兔心肌急性缺血再灌注损伤的保护作用。方法采取开胸结扎LAD(left anterior descending,左前降支)的急性心肌梗死模型,结扎冠状动脉LAD 30min后,松开结扎线,再灌注4 h。新西兰兔22只随机分成2组:①硬膜外吗啡组:经硬膜外注入吗啡(0.25 mg/kg,配成0.5 mL溶液);②对照组:经硬膜外注入生理盐水0.5 mL。缺血再灌注后逐层关胸,4周后行超声心动图检查。结果缺血再灌注后4周,两组LVEDD和LVESD均明显增大,但以对照组为甚,组间比较差异有显著性(P<0.05);而LVEF和LVFS,在缺血再灌注后4周硬膜外吗啡组分别降低了9.36%和8.24%,对照组分别降低了13.53%和12.18%,对照组比硬膜外组更显著(P<0.05),左室心功能硬膜外吗啡组好于对照组(LVEF:69.73%vs.62.99%;LVFS:31.39%vs.26.59%;LVEDD:14.35 vs.16.96;LVESD:9.52 vs.12.01),差异有统计学意义(P<0.05)。结论硬膜外注射吗啡能改善缺血再灌注后左心功能,并对缺血再灌注心肌有明显的保护作用。     

核因子-kappa B在肢体缺血预处理早期心肌保护中的作用

目的:探讨非创伤性肢体缺血预处理对缺血/再灌注心肌的作用及核因子kappa B(NF-kB)在诱导远隔器官预处理中的可能机制.方法:Wistar大鼠48只,制备心肌缺血/再灌注模型,随机分3组,缺血/再灌注组(I/R组),非创伤性肢体缺血预处理组(PL组),ProDTC非创伤性肢体缺血预处理组(PL-D组).观察各组心肌梗死面积,并应用反转录PCR技术,测定心肌组织NF-kB mRNA.结果:心肌梗死面积PL组较I/R组明显减少,分别为34.5%±7.6%和58.5%±8.5%(P<0.05),而PL-D组与I/R组相比无显著差异.与I/R组比较,PL组和PL-D组NF-kB mRNA表达明显减弱(P<0.05);PL-D组NF-kB mRNA表达较PL组亦明显减弱(P<0.05).结论:非创伤性肢体缺血预处理对缺血再灌注心肌有早期保护作用,NF-kB在肢体缺血预处理的早期心肌保护中起重要作用.     

缺血预处理及低温对幼兔心肌缺血/再灌注损伤的影响

目的：探讨缺血预处理(ischemic preconditioning,IP)及低温对幼兔心脏缺血／再灌注损伤的影响。方法：采用Langendorff离体心脏灌注模型,取3～4周龄幼兔心脏,分别给予不同次数的IP后使其在20℃低温下缺血或给予同样次数的IP后使其分别在不同低温下缺血。常温再灌注30min。记录心脏缺血／再灌注前后左心室功能指标,测定再灌注末心肌组织中ATP和丙二醛(MDA)含量,超氧化物歧化酶(SOD)及Ca^2 -ATP酶的活性。结果：再灌注末,IP2组左心室各功能指标的恢复率及心肌组织的ATP含量及Ca^2 -ATP酶的活性均显著高于Con组和IP3组;SIP1、SIP2组的左心室各功能指标的恢复率及心肌组织的ATP含量均分别显著高于SConn1组和SCon2组。其心肌组织MDA含量亦分别低于SCon1组和SCon2组。结论：IP可减轻低温缺血的幼兔心肌缺血／再灌注损伤,其效应与IP的次数和低温程度有关。     

桑叶总黄酮预处理对大鼠缺血再灌注损伤心肌抗氧化作用的研究

为研究桑叶总黄酮预处理对缺血再灌注损伤心肌的抗氧化作用,采用结扎左冠状动脉前降支30min,再灌注2h的方法制备大鼠心肌缺血再灌注损伤模型。将50只大鼠随机分为假手术组、缺血再灌注损伤模型组和桑叶总黄酮高、中、低剂量预处理组,每组10只。实验结束后,取动脉血和心脏。测定各组血清生化指标肌酸激酶(CK)和乳酸脱氢酶(LDH)的含量;测定心肌生化指标超氧化物歧化酶(SOD)的活性和丙二醛(MDA)的含量。结果显示,与模型组相比,桑叶总黄酮预处理组使血清中的CK、LDH含量明显降低,同时使心肌组织中的SOD活性提高,MDA含量降低。结果表明,桑叶总黄酮预处理对缺血再灌注损伤心肌有明显的保护作用,其机制可能与提高心肌SOD活性、清除自由基、增强抗氧化能力有关。     

尼可地尔预处理对大鼠缺血再灌注心肌mtDNA4834bp片段缺失的影响

目的:探讨尼可地尔预处理对大鼠缺血再灌注心肌mt DNA4834 bp缺失突变的影响。方法:体重200 g-300 g,7-9周龄健康雄性Sprague-Dawley(SD)大鼠50只,随机平均分为5组,假手术(Sham)组、心肌缺血再灌注损伤(MIRI)组、缺血预处理(IPC)组、尼可地尔(Nic)组、尼可地尔+5羟基葵酸钠(Nic+5-HD)组。建立心肌缺血再灌注模型后取心肌组织,提取mt DNA,应用巢式PCR法定性检测mt DNA4834 bp片段缺失突变。结果:MIRI组、IPC组、Nic组和Nic+5-HD组突变频率分别为100%、20%、30%和89%。Sham组未检测到mt DNA4834 bp缺失突变。Nic组mt DNA4834 bp片段缺失明显低于MIRI组和Nic+5-HD组(P0.05),与IPC组比较差异无统计学意义(P0.05)。结论:尼可地尔预处理可降低大鼠MIRI后mt DNA4834 bp片段缺失突变,改善线粒体能量衰竭。     

共载体AAV-PR39-ADM治疗缺血性心脏病

目的:探讨共载体AAV-PR39-ADM分泌表达血管生成肽(PR39)与血管扩张肽(ADM)对SD大鼠心肌缺血再灌注损伤的作用。方法:选健康成年雄性SD大鼠36只,体重平均为280 g±20 g,随机分为假手术组(SO)、治疗组(TR)与对照组(I/R),每组各12只。治疗组大鼠心肌注射共载体AAV-PR39-ADM感染心肌7天后行B超检查,测量记录左室壁厚度及射血分数(EF%),左室收缩末压(LVSP),左室内压最大上升下降速率(±dp/dt max)评价作为心脏功能指标。对照组建立缺血再灌注损伤模型,假手术组只穿线不结扎且两组行相同检测。速取处死大鼠心肌行masson染色测量心肌梗死面积。结果:治疗组明显高于对照组,其射血分数、左室内收缩末压、最大上升速率,最大下降速率、梗死面积分别为:EF%(50.4±6.3),(29.8±10.5),P0.05;LVSP:(116±4.2),(101±3.7),P0.05;+dp/dt max:(2859±365),(2137±191),P0.05;-dp/dtmax:(2186±107),(1886±124),P0.05;IS%:(29.3±4.6),(24.6±2.2),P0.05。结论:共载体AAV-PR39-ADM能够显著恢复心肌缺血损伤引起的左室内压下降,提高心肌收缩能力,提高射血分数并明显缩小心肌梗死范围。     

芹菜素对缺血再灌注大鼠心肌核转录因子-κB和ICAM-1表达的影响

目的研究芹菜素对缺血再灌注大鼠心肌核转录因子-κB(NF-κB)和粘附分子ICAM-1表达的影响,探讨其抗心肌缺血再灌注损伤的可能机制。方法将Wistar大鼠随机分为6组:假手术组、缺血再灌注组(IR组)、溶剂对照组、维拉帕米阳性对照组、芹菜素低、高剂量用药组。采用结扎左冠状动脉前降支制作缺血再灌注模型,心肌缺血30 min,再灌注2 h。免疫组化染色检测心肌组织的NF-κB和ICAM-1的表达.结果芹菜素组可降低心肌组织NF-κB和ICAM-1的表达,与IR组比较有显著差异(P0.05)。结论芹菜素对缺血再灌注心肌的保护作用可能与其减少心肌缺血再灌注后NF-κB和ICAM-的激活有关。     

一氧化氮在心肌缺血再灌注损伤中的作用

目的：观察一氧化氮（NO）对相对缺血再灌注心肌损伤的保护作用。方法：高频弱电流刺激法建立离体心肌相对缺血再灌注模型,设非缺血组和相对缺血组,相对缺血组包括对照、L－精氨酸（L－ARG）、硝基－L－精氨酸甲酯（L－NAME）三组。测定缺血前和再灌注时心功能变化、NO含量和乳酸脱氢酶同工酶－1（LD－1）活性。结果：L－ARG可明显促进再灌注期间NO合成,抑制D－1活性升高。再灌注40min时,L－ARG组心肌功能恢复程度明显高于对照组和L－NAME组（P＜0.05）,L－NAME使心肌NO含量降低（P＜0.05）,LD－1活性升高（P＜0.05）,心功能恢复程度最低。结论：NO可明显减轻心肌缺血再灌注时的细胞损伤,促进心功能的恢复。     

心肌缺血／再灌注损伤后血清和心肌组织Leptin水平的变能

目的：观察大鼠心肌缺血／再灌注损伤对血清和心肌组织瘦素（Leptin）表达的影响,探讨Leptin在心肌缺血／再灌注损伤中的作用。方法：建立大鼠心肌缺血／再灌注模型,检测血清乳酸脱氢酶（LDH）和Leptin浓度,并用HE染色和免疫组织化学观察心肌组织病理学及Lepfin表达水平。结果：缺血组、再灌注组血清LDH水平显著升高（P〈0．05）,表明该模型制作成功,造成心肌局部一定程度的损伤。缺血组血清Leptin含量（6．34±2．49）ng／ml显著低于对照组（7．50±2．93ng／ml,P〈0．05）;再灌注后Leptin水平缓慢恢复,于再灌注2h时Leptin达到（8．32±1．74）ng／ml,恢复到损伤前水平（8．38±2．56）ng／ml,且随再灌注时间延长有升高趋势。免疫纽化显示与假手术纽心肌Leptin蛋白表达水平相比,其他四组均有显著降低（P〈0．01）,按缺血45min后再灌注1h组、缺血45min后再灌注3h组、单纯缺血45min组、缺血45min后再灌注2h组依次递减。结论：Leptin在心肌缺血／再灌注损伤后早期45min血中有明显减少,心肌组织中也明显表达下降。心肌组织病理损伤与Leptin的改变可能有一定的关系。     

活性氧、NO和线粒体ATP敏感钾通道在TNF-α预处理对缺血/再灌注心肌保护中的作用

目的: 观察TNF-α预处理对缺血/再灌注心脏功能和酶学指标的影响及其可能机制.方法: 采用心脏Langendorff灌流模型.结果:与单独缺血/再灌注组相比,TNF-α(104U/L)预处理明显减弱缺血/再灌注对左室发展压、左室舒张末压、最大收缩/舒张速率和左室发展压与心率乘积的抑制作用(P<0.05),并显著降低复灌后冠脉流出液中乳酸脱氢酶(LDH)含量,增加线粒体中锰超氧化物歧化酶(Mn-SOD)活性(P<0.05);分别使用抗氧化剂2-MPG(0.3 mmol/L)、一氧化氮合酶抑制剂L-NAME(0.5 mmol/L)或线粒体ATP敏感钾通道抑制剂5-HD(100 μmol/L)预处理,减弱了TNF-α改善缺血/再灌注后心功能、抑制心肌LDH释放和诱导Mn-SOD活性增高的作用.结论: TNF-α预处理具有减轻心脏缺血/再灌注损伤的作用,这一作用可能与其诱导Mn-SOD活性增高有关,活性氧、一氧化氮和线粒体ATP敏感钾通道参与介导TNF-α的心肌保护作用.     

Glucose-insulin-potassium preserves systolic and diastolic function in ischemia and reperfusion in pigs

Clinical and experimental studies have suggested benefit of treatment with intravenous glucose-insulin-potassium (GIK) in acute myocardial infarction. However, patients hospitalized with acute coronary syndromes often experience recurrent myocardial ischemia without infarction that may cause progressive left ventricular (LV) dysfunction. This study tested the hypothesis that anticipatory treatment with GIK attenuates both systolic and diastolic LV dysfunction resulting from ischemia and reperfusion without infarction in vivo. Open-chest, anesthetized pigs underwent 90 min of moderate regional ischemia (mean subendocardial blood flow 0.3 ml x g(-1) x min(-1)) and 90 min reperfusion. Eight pigs were treated with GIK (300 g/l glucose, 50 U/l insulin, and 80 meq/l KCl; infused at 2 ml x kg(-1) x h(-1)) beginning 30 min before ischemia and continuing through reperfusion. Eight untreated pigs comprised the control group. Regional LV wall area was measured with orthogonal pairs of sonomicrometry crystals. GIK significantly increased myocardial glucose uptake and lactate release during ischemia. After reperfusion, indexes of regional systolic function (external work and fractional systolic wall area reduction), regional diastolic function (maximum rate of diastolic wall area expansion), and global LV function (LV positive and negative maximum rate of change in pressure with respect to time) recovered to a significantly greater extent in GIK-treated pigs than in control pigs (all P < 0.05). The findings suggest that the clinical utility of GIK may extend beyond treatment of acute myocardial infarction to anticipatory metabolic protection of myocardium in patients at risk for recurrent episodes of ischemia.     

11,12.环氧二十碳三烯酸预处理与后处理对缺血/再灌注大鼠心肌的保护作用

采用Langendorff离体灌流装置,通过停灌40 min/复灌30 min复制大鼠心肌缺血/再灌注(ischemia/reperfusion,IR)损伤模型,观察11,12-环氧二十碳三烯酸(11,12-epoxyeicosatrienoic acid,11,12-EET)预处理和后处理对心肌线粒体功能以及心功能的影响,探讨11,12-EET顸处理和后处理对IR大鼠心肌的作用及其机制.将30只Sprague-Dawley大鼠随机分为对照组、IR组、EET预处理组(Pre-EET)、EET后处理组(Post-EET),每组6只.除对照组外,其它各组全心缺血40 min,再灌注30 min.监测左心室内压差(ALVP)和左心室内压升降的最大变化率(±dp/dtmax)等心功能指标,测定灌流液中乳酸脱氢酶(1actate dehydrogenase,LDH)的活性.灌流结束后,测定心肌线粒体琥珀酸脱氢酶(succinate dehydrogenase,SDH)、Ca"ATPase、Na - K -ATPase活性以及心肌超氧化物歧化酶(superoxide dismutase,SOD)活性、丙二醛(malondialdehyde,MDA)含量.结果显示:(1)与IR组相比,Pre-EET组及Post.EET组Na -K -ATPase和SDH活性均增强,Ca2 -ATPase活性均减弱,有显著性差异(P<0.05);而Pre-EET与Post-EET组间没有显著性差异.(2)与IR组相比,Pre-EET组及Post-EET组心功能明显改善,LDH漏出显著减少,心肌SOD活性明显增强,MDA含量明显降低,有显著性差异(P<0.05);而Pre-EET与Post-EET组间没有显著性差异.结果表明,11,12-EET预处理及后处理均可通过上调心肌线粒体Na -K -ATPase、SDH活性以及下调Ca2 -ATPase活性改善线粒体功能和心肌能量代谢,拮抗心肌IR损伤;11,12-EET预处理及后处理还可通过提高心肌SOD活性、降低MDA含量改善IR心肌的氧化应激.     

肾缺血预处理对心脏缺血／再灌注损伤的保护作用

目的：探讨肾缺血预处理对家兔心脏缺血／再灌注（I／R）损伤的影响及意义。方法：32只大耳白家兔随机分为假手术（SO）、心脏I／R、经典缺血预处理（CIPC）及肾缺血预处理（RIPC）4组。观察各组心肌梗塞面积、左室舒缩功能、心脏超微结构及心律失常发生率的变化。结果：CIPC、RIPC组,心肌梗塞面积、再灌性心律失常发生率较I／R组明显降低,左室舒缩功能明显恢复（P＜0.01）,心脏超微结构损伤明显减轻。结论：RIPC可诱导出与CIPC类似的心脏保护效应。     

Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart

Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α(2)-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigate whether dexmedetomidine administration activates cardiac survival kinases and induces cardioprotection against regional ischemia/reperfusion injury. In in vivo and ex vivo models, rat hearts were subjected to 30 min of regional ischemia followed by 120 min of reperfusion with dexmedetomidine before ischemia. The α(2)-adrenergic receptor antagonist yohimbine was also given before ischemia, alone or with dexmedetomidine. Erk1/2, Akt and eNOS phosphorylations were determined before ischemia/reperfusion. Cardioprotection after regional ischemia/reperfusion was assessed from infarct size measurement and ventricular function recovery. Localization of α(2)-adrenergic receptors in cardiac tissue was also assessed. Dexmedetomidine preconditioning increased levels of phosphorylated Erk1/2, Akt and eNOS forms before ischemia/reperfusion; being significantly reversed by yohimbine in both models. Dexmedetomidine preconditioning (in vivo model) and peri-insult protection (ex vivo model) significantly reduced myocardial infarction size, improved functional recovery and yohimbine abolished dexmedetomidine-induced cardioprotection in both models. The phosphatidylinositol 3-kinase inhibitor LY-294002 reversed myocardial infarction size reduction induced by dexmedetomidine preconditioning. The three isotypes of α(2)-adrenergic receptors were detected in the whole cardiac tissue whereas only the subtypes 2A and 2C were observed in isolated rat adult cardiomyocytes. These results show that dexmedetomidine preconditioning and dexmedetomidine peri-insult administration produce cardioprotection against regional ischemia/reperfusion injury, which is mediated by the activation of pro-survival kinases after cardiac α(2)-adrenergic receptor stimulation.     

高氧液预处理对兔心肌缺血再灌注损伤的影响

目的:研究高氧液预处理对兔心肌缺血再灌注损伤的影响。方法:雄性新西兰白兔32只,随机分为4组(n=8),结扎-开放冠状动脉左前降支(LAD)建立心肌缺血再灌注模型。假手术组(Sham组)只穿线环绕LAD不结扎;吸氧组(OX组)结扎前30 min经鼻吸纯氧2L/min;在结扎LAD前30 min分别静脉注射HO 10 ml/kg(HO1组)、20 ml/kg(HO2组)。于结扎LAD前即刻(T0,基础值)、开放LAD前即刻(T1)、再灌注60 min(T2)及再灌注120 min(T3)时记录HR和MAP,于T3时抽取动脉血样3 ml,测定血清肌酸激酶(CK)、肌钙蛋白I(cTNI)的活性和IL-6和TNF-α的浓度,并测定心肌梗死范围。结果:I/S组与T0时比较,T 1-3时各组HR、MAP进行性下降(P<0.05);三组间HR、MAP比较差异无统计学意义(P>0.05)。与Sham组比较,I/S组血清CK、cTNI、IL-6和TNF-α含量明显升高(P 0.01);与OX组比较,HO2组上述酶及炎症因子浓度显著下降(P<0.01),心肌梗死范围减小(P<0.05)。结论:高氧液预处理可减轻兔心肌缺血再灌注损伤,机制可能与其抑制炎性反应有关。     

罗布麻通过抑制氧化应激反应减轻心肌缺血再灌注损伤

目的:观察罗布麻叶提取物(apocynum venetum leaf extract AVLE)预处理对心肌缺血再灌注(MI/R)损伤的影响。方法:采用SD大鼠MI/R模型,随机分为sham(假手术)组、MI/R组、AVLE预处理+MI/R组,检测血流动力学,采用氯化三苯基四氮唑和伊文思蓝双染法检测心梗面积、以血浆肌酸激酶(CK)和乳酸脱氢酶(LDH)活性检测心肌损伤情况、以超氧化物、丙二醛(MAD)和超氧化物歧化酶(SOD)含量检测心肌氧化应激以及Western blot方法检测gp91phox的表达。结果:与MI/R组相比,AVLE预处理组左室压上升、下降最大速率(±LVdp/dtmax)升高(P0.05),心肌梗死面积减少,两组分别为41.5±4.5%和32.0±3.5%(P0.05),血浆CK和LDH活性分别降低到1653±62 U/L和2461±152 U/L(P0.05),减少了心肌组织超氧化物的含量(P0.05)。AVLE治疗显着降低gp91phox的表达(P0.05),使SOD活性增加(P0.05),MDA水平显著降低(P0.05)。结论:AVLE通过抑制I/R心肌的氧化应激发挥心脏保护作用。     

Noradrenaline dynamics in prolonged ischemia after ischemic preconditioning

AIM OF THE STUDY: To determine the effects of two-staged ischemic preconditioning on myocardial noradrenaline in prolonged ischemia and reperfusion. METHODS: Thirty-two male Wistar rats anesthetised with urethane randomly divided into 2 groups: group 1 (ischemic preconditioning group, n = 16), and group 2 (control, n = 16). Myocardial interstitial noradrenaline levels were measured using a microdialysis technique. Ischemic preconditioning was elicited by two episodes: 5 min of ischemia and 10 min of reperfusion. The intermittent occlusions were followed by prolonged occlusion (60 min) and reperfusion (60 min). RESULTS: An increase in interstitial noradrenaline was observed in 10 min of prolonged ischemia in group 2, and in 20 min in group 1. After 20 min of myocardial ischemia there was a significant difference between groups (p < 0.05) in interstitial noradrenaline levels. In control group, it was 60% higher. In reperfusion, noradrenaline levels decreased markedly in group 1. CONCLUSION: We suggest that ischemic preconditioning by two episodes: 5-min ischemia and 10-min reperfusion prevents excessive noradrenaline interstitial accumulation, perhaps, through protection of physiological uptake I carrier.     

Does coronary vasodilation after adenosine override endothelin-1-induced coronary vasoconstriction?

In vivo evaluation of the transmural extension of myocardial infarction (TEI) is crucial to prediction of viability and prognosis. With the rise of transgenic technology, murine myocardial infarction (MI) models are increasingly used. Our study aimed to evaluate systolic strain rate (SR), a new parameter of regional function, to quantify TEI in a murine model of acute MI induced by various durations of ischemia followed by 24 h of reperfusion. Global and regional left ventricular (LV) function were assessed by echocardiography (13 MHz, Vivid 7, GE) in 4 groups of wild-type mice (C57BL/6, 2 mo old): a sham-treated group (n = 10) and three MI groups [30 (n = 11), 60 (n = 10), and 90 (n = 9) min of left coronary artery occlusion]. Conventional LV dimensions, anterior wall (AW) thickening, and peak systolic SR were measured before and 24 h after reperfusion. Area at risk (AR) was measured by blue dye and infarct size (area of necrosis, AN) and TEI by triphenyltetrazolium chloride staining. AN increased with ischemia duration (25 +/- 2%, 56 +/- 5%, 71 +/- 6% of AR for 30, 60, and 90 min, respectively; P < 0.05). LV end-diastolic volume significantly increased with ischemia duration (30 +/- 5, 34 +/- 5, 43 +/- 5 microl; P < 0.05), whereas LV ejection fraction decreased (63 +/- 5%, 58 +/- 6%, 46 +/- 5%; P < 0.05). AW thickening decrease was not influenced by ischemia duration. Conversely, systolic SR decreased with ischemia duration (13 +/- 5, 4 +/- 3, -2 +/- 6 s(-1); P < 0.05) and was significantly correlated with TEI (r = 0.89, P < 0.01). Receiver operating characteristic (ROC) curves identified systolic SR as the most accurate parameter to predict TEI. In conclusion, in a murine model of MI, SR imaging is superior to conventional echocardiography to predict TEI early after MI.     

Role of kappa-opioid receptor activation in pharmacological preconditioning of swine

Pharmacological preconditioning with kappa-opioid receptor agonists is proarrhythmic and exerts antipreconditioning effects in rats. In swine, it is unknown whether kappa-opioid receptor stimulation plays a role in pharmacological preconditioning. Swine were preconditioned with 1) saline (controls), 2) [d-Ala(2),d-Leu(5)]enkephalin (DADLE), 3) morphine, 4) pentazocine, 5) norbinaltorphimine (nor-BNI), 6) DADLE + nor-BNI, 7) morphine + nor-BNI, or 8) pentazocine + nor-BNI before occlusion (45 min) and reperfusion (180 min) of the left anterior descending coronary artery. Infarct size to area at risk (IS), regional (systolic shortening) and global (pressures and flows) myocardial function, and arrhythmia occurrence were assessed. Only DADLE + nor-BNI preconditioning significantly decreased infarct size compared with controls (47 +/- 13 vs. 65 +/- 5%, P < 0.05); morphine preconditioning was not cardioprotective with or without kappa-opioid receptor blockade (nor-BNI). DADLE preconditioning significantly increased ischemia-induced arrhythmias relative to controls, whereas pentazocine-preconditioned animals (n = 2) experienced intractable ventricular fibrillation during ischemia. kappa-Opioid receptor blockade with DADLE or pentazocine preconditioning alleviated proarrhythmic effects. These results suggest that kappa-opioid receptor activation during pharmacological preconditioning is proarrhythmic in swine.     

Effects of a bradycardic agent on postischemic cardiac recovery in rabbits.

Decreasing heart rate might be beneficial for improvement of myocardial energetics and could reduce the severity of myocardial ischemia. We examined the contribution of heart rate reduction by cilobradine (DK-AH 269), a direct sinus node inhibitor, on left ventricular function and peripheral vasomotion in anesthetized rabbits with experimental myocardial infarction. The rabbits were randomized to receive either placebo (n=10) or cilobradine (n=7). Cilobradine decreased significantly heart rate from 163 +/- 33 to 131 +/- 13 bpm, p< 0.05, without any inotopic or vascular effects. After 60 min coronary occlusion and 30 min reperfusion, both systolic and diastolic ventricular function were more reduced in the cilobradine group; i.e. maximal left ventricular pressure significantly decreased to 62 +/- 11 mmHg, p < 0.05 (placebo: 77 +/- 9 mmHg); dP/dt(min) significantly decreased to -904 +/- 247 mmHg, p < 0.05 (placebo: -1106 +/- 242 mmHg). However, infarct size in the cilobradine group was significantly smaller compared with the placebo group. In conclusion, cilobradine reduced heart rate without any negative inotropic effect and reduced infarct size. On that account, this bradycardic agent might open a promising therapeutical avenue to treat postischemic dysfunction.