川芎嗪对缺血再灌注所致大鼠离体心脏损伤的保护作用

目的:观察川芎嗪对缺血再灌注所致大鼠离体心脏损伤的保护作用。方法:心脏缺血再灌注模型:大鼠离心脏Langen-dorff灌流,全心停灌20分钟后复灌40分钟造成缺血--再灌注损伤。将充水乳胶球囊通过左心房插入左心室,Medlab-u/81生物信号采集处理系统记录分析心功能指标LVP,±dp/dtmax,HR和CF,收集再灌5分钟时,冠脉流出液。用分光光度法测定肌酸激酶(CK)活性。结果:缺血再灌注能降低冠脉流量,LVP,±dp/dtmax值,减慢心率、增加CK释放量,两个浓度的川芎嗪(40与80mg·L-1)对离体大鼠心脏缺血再灌注损伤有保护作用,表现为改善心功能,增加冠脉流量,减少心肌细胞内酶CK的释放,川芎嗪与维拉帕米有相似的心肌保护作用。结论:川芎嗪对心脏缺血再灌注心功能损伤具有保护作用。     

硫化氢对大鼠离体灌流心脏心功能的影响

目的：观察H2S对大鼠离体心脏心功能的影响，以探讨内源性H2S对心肌活动的调节意义。方法： 检测大鼠心肌组织中H2S的含量及生成率，并采用RT-PCR方法检测心肌组织CSE(内源性硫化氢合成的关键酶)mRNA的表达；应用Langendorff灌流大鼠离体心脏，用不同浓度NaHS(10-6-10-3mmol/L)灌流心脏，及用生理浓度NaHS(4×10-4mol/L)持续灌流20 min，测量心率(HR)、左室内压差(△LVP＝左室收缩压-左室舒张压)、左室内压变化速率(±dp/dtmax)、冠脉灌流量(CPF)等指标；应用KATP通道阻断剂格列苯脲预灌流，后给予生理剂量NaHS灌流，观察其是否可以阻断NaHS的效应。结果： NaHS可以呈浓度依赖性抑制左心室±dp/dtmax及△LVP(P＜0.05)，但对HR、CPF没有影响，生理剂量NaHS持续灌流20 min内，可以持续抑制±dp/dtmax及△LVP(P＜0.05)，而对HR、CPF几乎没有影响。KATP通道阻断剂格列苯脲可以大部分(85.7%)阻断生理剂量NaHS对心功能的抑制效应。结论： 内源性H2S可能通过开放心肌KATP通道，抑制大鼠离体心脏左心室的收缩功能。     

甘氨酰谷氨酰胺在大鼠离体心脏缺血/再灌注损伤中的保护作用研究

目的： 研究甘氨酰谷氨酰胺对缺血再灌注大鼠离体心脏的保护作用。方法：应用Langendorff离体心脏灌注系统建立心肌缺血再灌注模型。30只SD雄性大鼠随机分为正常对照组(control)、甘氨酰谷氨酰胺对照组(Gly-Gln)、缺血再灌注组(I/R)、缺血/再灌注+甘氨酰谷氨酰胺组(I/R+ Gly-Gln)。I/R组及I/R+ Gly-Gln组分别灌注30 min后,全心停灌20 min,再灌注40 min,I/R+ Gly-Gln组于再灌注时在灌流液中加入Gly-Gln;正常对照组连续灌流90 min,Gly-Gln对照组灌流液中加入Gly-Gln。记录各组灌注时,左室舒张末压(LVEDP)、左室发展压(LVDP)、左室压力最大变化速率(±dp/dtmax)、心率(HR)及心肌细胞单相动作电位(MAP);同时在相应的时点分别测定冠脉流出液中的乳酸脱氢酶（LDH)、肌酸激酶(CK)活性。结果：离体大鼠心脏缺血20min,再灌注40 min,导致严重的心功能抑制,表现为LVEDP升高,LVDP、±dp/dtmax降低;再灌注液中加入Gly-Gln后,LVEDP降低,LVDP、±dp/dtmax明显升高（P<0.01)。I/R+ Gly-Gln组冠脉流出液中LDH、CK活性明显低于I/R组(均P<0.01)。结论： Gly-Gln能有效减轻缺血再灌注引起的左室功能下降,减少心肌细胞LDH、CK的释出,表明Gly-Gln对缺血再灌注损伤的大鼠离体心脏具有保护作用。     

耗竭心肌细胞内糖原对缺血后再灌注心肌的保护作用及其机制

本工作在离体大鼠等容收缩心脏模型上观察耗竭心脏细胞内糖原对心肌缺血再灌注损伤的影响。心脏富氧灌流30 min后,随机分为三组:Ⅰ、富氧组:富氧灌流75min。Ⅱ、对照组:常规K-H液富氧灌流15min,旷置30min,再灌流30min。Ⅲ、耗竭糖原组:先用充N_2(95%N_2:5%CO_2)的K-H液灌流15min,余同组Ⅱ。结果表明。耗竭心肌细胞内糖原可提高再灌注后心脏血液动力学的恢复;冠脉流出液中LDH活性及心肌组织MDA含量降低,线粒体及胞浆液中GSH-Px有较高的活性;心肌组织Na~+,Ca~(2+)超负荷减轻。说明耗竭心肌细胞内糖原可通过减少细胞内H~+的生成抑制Na~+/H~+交换,从而明显减轻心肌缺血再灌注损伤。     

地高辛抗血清拮抗内洋地黄素介导的离体大鼠心肌缺氧复氧损伤的实验研究

目的：研究内洋地黄素在离体大鼠心脏缺氧复氧损伤中的变化，观察内洋地黄素特异性拮抗剂地高辛抗血清对大鼠心脏缺氧复氧损伤（A-RI）的拮抗作用。 方法： 制备离体大鼠心脏A-RI模型，60只SD 大鼠随机分为6组，每组10只。正常对照组：给予富氧K-H液灌流，流量10 mL·min-1，持续灌流90 min；A-RI组：富氧K-H液灌流30 min后，予以乏氧K-H液低流量（1-2 mL·min-1）灌流30 min，再给予富氧K-H液复灌30 min；维拉帕米组、小剂量、中剂量、大剂量地高辛抗血清组：于复氧前分别向灌流液中加入维拉帕米5 μg·kg-1、地高辛抗血清3.3 mg·kg-1、10 mg·kg-1、30 mg·kg-1，复氧灌流前灌注完，其余同A-RI组。各组于复氧灌流结束时，制备心肌匀浆，测定心肌匀浆中内洋地黄素含量、细胞膜Na+-K+-ATP酶活性以及线粒体总Ca2+水平，并观察心肌超微结构的变化。 结果： A-RI组心肌组织内洋地黄素水平明显高于正常对照组［（1.04±0.42）ng·g-1与（0.63±0.09）ng·g-1，P<0.01］，细胞膜Na+-K+-ATP酶活性明显低于正常对照组［（2.85±1.00) mmol·g-1Pr·h-1与（4.24±1.19)mmol·g-1Pr·h-1，P<0.01］，线粒体总Ca2+水平显著高于正常对照组［（0.368±0.113) μmol·g-1Pr·h-1与（0.130±0.004) μmol·g-1Pr·h-1，P<0.01］，心肌组织结构发生明显破坏。中、大剂量地高辛抗血清组心肌组织内洋地黄素水平显著低于A-RI组［（0.55±0.24)ng·g-1，(0.68±0.26) ng·g-1］，心肌组织Na+-K+-ATP酶活性显著高于A-RI组［（4.88±1.51)mmol·g-1Pr·h-1，（3.85±1.15)mmol·g-1Pr·h-1），心肌线粒体内总Ca2+含量显著低于A-RI组［（0.127±0.026)nmol·g-1Pr·h-1，（0.156±0.050)μmol·g-1Pr·h-1］，显著减轻A-RI导致的心肌组织结构的损伤。 结论： 地高辛抗血清对A-RI心肌有明显的保护作用，其作用机制可能通过拮抗内洋地黄素，恢复心肌细胞膜Na+-K+-ATP酶活性，减轻细胞内钙超载。     

Amiloride对低血流缺氧再灌注心肌的保护作用

本文采用离体大鼠等容收缩心脏模型,探讨Na/H交换机制在心脏低血流缺氧后再灌注损伤中的意义。心脏富氧灌流30min后,随机分为三组:(1)富氧组:富氧灌流75 min;(2)对照组:低血流缺氧45 min后再恢复富氧灌流30 min;(3)Amiloride组:低血流缺氧期间,溶0.5(mmol/L)Amiloride(Na/H交换抑制剂)于K-H液中,余同组(2)。实验发现Amiloride组心脏各血液动力学指标优于对照组,冠脉流出液中LDH活性及心肌组织MDA含量均少于组(2),线粒体及胞浆液中GSH-Px活力得以保护,心肌组织Na~ 、Ca~(2 )超负荷减轻,K~ 丢失减少。结果表明:抑制Na~ /H~ 交换能明显减轻低血流缺氧心肌再灌注损伤。     

不同保存液对离体大鼠心脏保存效果的研究

目的:研究在冷缺血期3种液体对鼠心脏保存的效果。方法:将24只大鼠随机分为3组,每组8只。3组离体鼠心脏分别用Histidine-tryptophan-ketoglurate(HTK)液,UniversityofWisconsin(UW)液及St.ThomasⅡ(ST)液灌注停跳,并4℃冷冻保存6h。利用离体鼠心非循环式Langendorff灌流功能测定模型,测定左心室舒张期末压(LVEDP)、左心室发展压(LVDP)、左心室压力变化率(dp/dt_max,dp/dtmin)、冠脉流出量(CF),留取冠脉流出液检测心肌酶漏出量,并检测心肌线粒体三磷酸腺苷(ATP),取心肌标本测干湿比。结果:HTK组保存的心肌左心室功能恢复明显优于UW组(P＜0.05),UW组明显优于ST组(P＜0.05),LVEDP恢复HTK组和ST组无显著差异(P＞0.05),但均较UW组恢复好(P＜0.05)。保存后心肌ATP测定值HTK组高于UW组(P＜0.05),UW组高于ST组(P＜0.05)。3组心肌标本测干湿比结果无显著差异(P＞0.05)。结论:HTK液保存心肌效果最好,含有高钾的保存液对冠脉有损害。     

HSP90依赖的Akt线粒体转位参与IGF-1对低温保存心脏的保护作用

目的: 观察胰岛素样生长因子1(IGF-1)是否可对抗低温保存诱导的心肌损伤,并探讨其可能的机制。方法: 观察SD大鼠心脏低温保存9 h后,再灌注期左心室发展压(LVDP)和细胞凋亡指数的变化。Western blotting法检测蛋白激酶B(Akt)蛋白表达。结果: (1)Celsior保存液中加入10 nmol/L IGF-1可促进低温保存9 h后心脏收缩功能的恢复、减少心肌细胞凋亡的发生、抑制线粒体渗透性转换孔开放。(2)IGF-1可上调心脏Akt蛋白磷酸化水平。磷脂酰肌醇3-激酶(PI3K)特异性抑制剂LY294002不仅可降低IGF-1诱导的Akt磷酸化水平,且可逆转IGF-1促进低温保存心脏心功能的恢复和抗凋亡作用。(3)抑制热休克蛋白90(HSP90)可降低IGF-1诱导的Akt磷酸化和线粒体转位,阻断IGF-1的心肌保护作用。结论: IGF-1可明显减少低温保存心脏心肌细胞凋亡的发生,促进再灌注期心功能的恢复,其机制可能与HSP90依赖性Akt的激活和线粒体转位有关。     

血浆ET与ANF在急性胰腺炎早期发病中的作用及意义

目的探讨内皮素(ET)与心钠素(ANF)在急性胰腺炎(AP)早期发病中的作用及临床意义.方法采用放射免疫分析测定急性发病期(24～48)h轻症急性胰腺炎(MAP)35例,重症急性胰腺炎(SAP)17例和正常对照组(NC)30例的血浆内皮素与心钠素的含量.Imrie评分＞3分,APACHE Ⅱ评分≥8分者为SAP.结果SAP患者Imrie评分和APACHE Ⅱ评分明显高于MAP患者(P＜0.05,P＜0.01).SAP患者血浆ET水平(59.20±10.69)pg/ml明显增高,MAP患者血浆ET水平(34.20±9.44)pg/ml明显降低,两组之间比较以及与NC组比较具有非常显著差异(P＜0.001).SAP和MAP患者血浆ANF分别为(155.76±34.24)pg/ml,(181.59±58.15)pg/ml,与NC组(165.51±57.16)pg/ml比较无明显变化(P＞0.05).结论ET可能参与了SAP早期胰腺微循环障碍,对胰腺组织具有内源性损伤作用.提示早期给予拮抗ET或ET-A受体的药物,可能有利于减轻胰腺组织损害,改善胰腺微循环,防止胰腺出血坏死性改变.ANF可能对AP早期的胰腺血循环无明显影响.     

葡萄糖、乳酸和丙酮酸对心肌线粒体氧耗动态适应的影响

目的 :了解外源性碳源物对心肌氧化磷酸化动态调节的影响。方法 :采用VanBeek建立的心肌线粒体平均氧耗反应时间 (tmito)测定方法 ,以葡萄糖、乳酸和丙酮酸分别为心肌供能的碳源物 ,用 37℃的Tyrode液灌流离体兔心脏进行实验。结果 :心率由 12 0分别增至 140和 2 2 0 (min-1)。测得的tmito:葡萄糖为 (6 3± 1 0 )s和 (7 4± 0 9)s ;乳酸为 (5 4± 1 2 )s和 (7 0± 0 9)s;丙酮酸为 (4 0± 0 7)s和 (6 5± 0 6 )s (tow -wayANOVA ,P<0 0 5 ,与葡萄糖 ,乳酸比较 )。结论 :心肌线粒体氧化磷酸化在心肌ATP利用快速变化的动态适应过程中 ,还原当量向线粒体内的转运可能是动态适应的限速因素。     

依达拉奉对离体大鼠心肌缺血再灌注损伤的保护作用

目的:探讨依达拉奉(ED)预先给药对大鼠离体心肌缺血再灌注(I/R)损伤的作用及其机制。方法:制作Langendorff主动脉逆行灌注心脏I/R模型。24只雄性大鼠随机分为三组(n均=8):对照组(C组)、I/R组、ED组。观察各组大鼠I/R后心功能指标:左室收缩峰压(LVSP)、左室压上升最大速率(+dp/dtmax)、左室压下降最大速率(-dp/dtmax)、冠脉流量(CF)、心肌细胞乳酸脱氢酶(LDH)及肌酸激酶同工酶(CK-MB)活性、心肌组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:与基础值和C组比较,I/R组再灌注时各时点的CF、LVSP、+dp/dtmax、-dp/dtmax降低(P<0.05);与I/R组比较,ED组再灌各时点的CF、LVSP、+dp/dtmax、-dp/dtmax增高(P<0.05);ED组心肌SOD活性明显高于I/R组(P<0.05),LDH及CK-MB活性、MDA含量低于I/R组(P<0.05)。结论:ED对I/R心肌有保护作用,能促进心功能恢复。其机制与清除自由基和减轻氧化应激有关。     

菊米提取液对抗心肌缺血再灌注损伤

目的： 研究菊米提取液的抗心肌缺血作用及其机制。方法：采用离体大鼠心脏Langendorff灌流模型，观察心脏收缩功能和心肌梗死面积。结果：（1）菊米提取液(0.5、1.0、2.0 g/L)灌流心脏后，左室发展压（left ventricular developed pressure，LVDP）、最大左室收缩/舒张速率（maximal rate of increase/decline in left ventricular pressure，±dp/dtmax）和冠脉流量增高。（2）菊米提取液可浓度依赖性增加心肌组织一氧化氮合酶（nitric oxide synthase，NOS）活性和一氧化氮（nitric oxide，NO）含量。（3）在缺血前（预处理）或再灌注早期给予0.5 g/L菊米提取液，均可减轻缺血再灌注引起的收缩功能下降，并可缩小心肌梗死面积。预先给予L-NAME，可取消菊米对抗心肌缺血再灌注损伤。结论：菊米提取液具有强心作用。菊米提取液能对抗心肌缺血再灌注损伤，其机制可能依赖于NO途径。     

Ischemic preconditioning triggers nuclear translocation of thioredoxin and its interaction with Ref-1 potentiating a survival signal through the PI-3-kinase-Akt pathway

Thioredoxin (Trx-1), a key mediator of cellular redox homeostasis and cell survival, is implicated in redox signaling in the ischemic myocardium. To investigate further its mechanism of action, Trx expression in rat heart was suppressed by direct injection of small hairpin RNA against Trx-1 (shRNA-Trx-1). Forty-eight hours after treatment, hearts were excised for isolated working-heart preparation. A group of hearts was preconditioned (PC) by subjecting them to four cyclic episodes of 5-min ischemia, each followed by 10 min of reperfusion. All the hearts, PC or non-PC, were subjected to 30-min ischemia followed by 2 h of reperfusion. As expected, the PC hearts exhibited improved ventricular function, reduced infarct size, and cardiomyocyte apoptosis. Also in PC hearts, an increase was noted in Trx-1 and other cardioprotective and redox-regulated proteins like Ref-1, phospho-Akt, and NF-kappaB DNA-binding activity. PC also caused nuclear translocation of Trx-1 and Ref-1 followed by their association. However, in hearts treated with shRNA-Trx 1, the cardioprotective effects of PC were abolished along with a concomitant decrease in nuclear localized Trx-1 and Ref-1, along with a decrease in phospho-Akt and NF-kappaB. These results demonstrate that PC triggers translocation of Trx-1 into the nucleus, where it becomes associated with Ref-1 and performs redox signaling through the activation of NF-kappaB and an increase in prosurvival signal inducer phospho-Akt.     

Effects of physical exercise and anti-G suit inflation on atrial natriuretic factor plasma level

Summary The purpose of this study was to measure the effect of enhanced venous return on atrial natriuretic factor (ANF) secretion during exercise and upright posture and the consequences on renin angiotensin aldosterone system (RAAS) activity. Six healthy male subjects were submitted to four different procedures. All procedures were performed in the same position, i.e. riding on a support with legs hanging. Two procedures were performed at rest: the subjects were studied after a 25-min rest in this position, with and without the lower limb fitted with an anti-G suit inflated to 60 mmHg. Two procedures were carried out with physical exercise; arm-cranking was performed in the same position with and without the anti-G suit inflated to 60 mmHg. Venous blood was collected before and after each procedure in order to measure plasma ANF, plasma aldosterone concentration (PAC), plasma renin activity (PRA), corticotrophin (ACTH) and catecholamine level. The data mean ±SEM showed that the ANF plasma level decreased significantly (p<0.05) from 32.5±4 to 28±6 pg · ml⁻¹ after a 20-min rest in the upright posture, whereas this effect was absolished with anti-G suit inflation. Physical exercise with and without the anti-G suit increased the ANF level above control values (60±13.6 pg · ml⁻¹ and 53±13 pg · ml⁻¹): anti-G suit inflation had no significant effect. PRA increased after rest in an upright posture and during physical exercise; anti-G suit inflation abolished this increase in both conditions. PAC was not influenced by postural change but significantly increased in all exercise tests. ACTH increased to the same extent in both exercise tests. The plasma catecholamine level increased during upright posture and both physical exercise procedures. These results indiate that enhanced venous return during anti-G suit inflation increases ANF secretion at rest in an upright posture and that physical exercise greatly increases plasma ANF level independently of the anti-G suit inflation. They suggest that ANF release during exercise could be influenced by factors other than haemodynamic stimuli. The comparison between ANF and PRA changes during arm-cranking indicates that PRA is influenced more than ANF by blood volume displacement. The ANF increase during exercise does not inhibit aldosterone secretion.     

Zn~(2+)预处理对离体大鼠缺血再灌注损伤心肌的保护作用

目的 :观察Zn2 + 预处理诱导金属硫蛋白 (MT)在心肌细胞的表达及对离体大鼠缺血再灌注损伤心肌的保护作用。方法 :3 2只Sprague Dawley大鼠随机分为对照组及实验组 ,实验组按腹腔注射ZnSO4 到建立再灌注模型的时间分为E1 2h,E2 4h及E4 8h组 ,每组各 8只。检测LDH ,CK、ATP含量及心功能指标 (LVSP与±dp/dtmax) ,用1 0 9Cd/血红素饱和法测量心肌组织中金属硫蛋白的含量。结果 :E2 4h及E4 8h组MT表达量较对照组高 (P <0 .0 1) ,E1 2h组虽有表达 ,但其与对照组间差异无显著性。E2 4h及E4 8h组LDH与CK较其它二组低 ,而ATP较其它二组高 ,心功能指标较其它二组改善。E1 2h组及对照组之间相应各指标 (LDH ,CK、ATP、LVSP与±dp/dtmax)间差异无显著性 (P >0 .0 5 )。结论 :Zn2 + 预处理可诱导MT在心肌细胞的表达而对离体大鼠缺血再灌注损伤心肌具有保护作用。     

同种异体脂肪组织源性间质干细胞移植治疗大鼠急性心肌梗死

目的：建立体外分离扩增脂肪组织源性间质干细胞方法，并探讨同种异体脂肪干细胞移植治疗大鼠心肌梗死的效果及可行性。方法: 18只雄性SD大鼠随机分为假手术组、急性心肌梗死对照组（AMI组）及AMI+细胞移植组。分离大鼠腹部脂肪组织干细胞，体外扩增，BrdU标记后于结扎左冠状动脉前降支后1h移植入梗死心肌，移植后4周进行血流动力学检测心功能并取出心脏进行病理切片观察和免疫组织化学染色检测移植细胞在梗死心脏中的定居、存活情况。结果: 大鼠腹部脂肪组织可分离培养出大量间质干细胞。细胞移植治疗组左心室收缩压高于AMI对照组（P＜0.01），舒张末压显著降低（P＜0.01），左心室内压最大上升、下降速率明显加快（P＜0.05）；病理组织切片显示梗死边缘区心肌面毛细血管计数明显增加，梗死区心肌组织内及毛细血管壁中均可见移植标记细胞。结论: 脂肪组织可作为干细胞又一新的来源，同种异体脂肪干细胞移植治疗AMI有效、可行。     

阿托伐他汀对兔急性心肌梗死再灌注后一氧化氮、内皮素-1水平及心功能的影响

目的:评价阿托伐他汀对兔急性心肌梗死再灌注(AMI/R)后一氧化氮(NO)、内皮素-1(ET-1)水平的影响及对心功能的作用。方法:新西兰大白兔24只随机分成AMI/R组、阿托伐他汀治疗组(5mg·kg-1.d-1)和假手术组,每组8只。冠状动脉结扎60min,松解120min制备AMI/R模型。梗死前、后和再灌注后均行血流动力学测定,采用硝酸还原酶法检测血浆及心肌组织NO水平,采用放射免疫方法测定血浆及心肌组织ET-1水平。结果:(1)与AMI前相比较,AMI/R组AMI60min和再灌注后120min,心率(HR)、主动脉收缩压(SBP)和舒张压(DBP)、左室收缩压(LVSP)、左心室内压最大收缩和舒张变化速率(±dp/dtmax)及心排量(CO)均显著下降,左室舒张末压(LVEDP)显著升高(P0.05或P0.01)。与AMI前相比,阿托伐他汀治疗组AMI60min和再灌注后120min上述各项指标变化与AMI/R组的变化趋势相似(P0.05或P0.01),但再灌注后120minLVSP、LVEDP、±dp/dtmax及CO比AMI60min有显著恢复(P0.01),且比AMI/R组恢复更显著(P0.05或P0.01);另外,治疗组SBP、DBP下降幅度明显低于AMI/R组(P0.01)。(2)与AMI/R组相比,阿托伐他汀能使AMI再灌注后血浆NO水平显著升高,ET-1水平显著降低(P0.01);而心肌组织NO、ET-1的含量治疗组仅复流区显著降低(P0.05或P0.01)。(3)与AMI/R组相比,阿托伐他汀可促进AMI后心功能的恢复。结论:阿托伐他汀能使缺血再灌注后血浆及心肌NO水平显著升高,ET-1水平显著降低,具有内皮保护作用;可促进AMI后心功能的恢复。     

A fetal mouse model of ventricular non-compaction using retinoic acid

ObjectiveTo develop a fetal mouse model of non-compaction of ventricular myocardium (NVM) using All-trans retinoic acid (ATRA).MethodsPregnant mice were divided into blank control group, dimethyl sulfoxide (DMSO) control group and ATRA group. The pregnant mice at 8.5 days after pregnancy were given 70 mg/kg ATRA in DMSO to induce fetal mouse model of NVM in ATRA group. All the hearts were acquired and sliced in short axis from the neonatal mice sacrificed after delivery. Pathological changes were visualized under 40- and 100-fold magnification with Hematoxylin-eosin (HE) staining at different ventricular levels. The criteria for pathological diagnosis of classical NVM were: prominent trabeculations on the endocardial surface and deep intertrabecular recesses communicating with the ventricular cavity and the thickness ratio of non-compacted layer (N) to compact myocardium layer (C) N/C > 1.4. Analysis of variance (ANOVA) and least significant difference (LSD) were used to analyze the differences of three groups, with P < 0.05 considered as significant.ResultsThe typical characteristics of NVM histopathological findings of ATRA fetal mouse were confirmed: compared to the hearts of blank control group (n = 20) and DMSO control group (n = 15), all the hearts of ATRA group (n = 17) showed the obviously thinner compacted layer and the much thicker non-compacted layer. The N/C ratio of left ventricles (LVs) in ATRA group was 2.735 ± 1.634, higher than those in DMSO control group 0.178 ± 0.119 and blank control group 0.195 ± 0.118 with significant difference (F = 32.550, P <0. 0001); N/C ratios of right ventricles (RVs) in the ATRA group were (6.068 ± 4.394), higher than those in the DMSO control group 0.459 ± 0.24 and in the blank control group 0.248 ± 0.182 with significant difference (F = 20.069, P <0.0001). LSD of LVs and RVs showed a significant difference between ATRA and blank control group (P < 0.0001), and between ATRA and DMSO control group (P < 0.0001). LSD showed no significant difference in two control groups of LVs (P = 0.963) and of RVs (P = 0.848) .ConclusionExcess ATRA could be used to induce NVM of fetal mice heart. This animal model might provide a platform for fundamental research of NVM pathogenesis and potential targeting treatment.     

Histamine release and its effects in ischaemia-reperfusion injury of the isolated rat heart

Histamine is released from the heart during ischaemia-reperfusion injury. As histamine has cardiac effects, we investigated the role of histamine in ischaemia-reperfusion injury of isolated rat hearts. A Langendorff-model with 30 min global (37 ^oC) ischaemia followed by 60 min reperfusion was employed. The effects of ischaemia alone (n= 10, group 1.1+n = 10, group 2.1, 2 different series), and ischaemia with H₁- and H₂-receptor blockade with cimetidine (10 μM, n= 10), chlorpheniramine (10 μm, n= 8), terfenadine (10 μM, n= 8), and promethazin (10 μM, n= 9), or both cimetidine and chlorpheniramine (n = 8), were studied. Histamine was measured in the coronary effluent and cardiac tissue of group 1.1. Release of histamine increased from 6.5 ± 1 pmol min^-1 before ischaemia to 19 ± 3 pmol min^-1 at the start of reperfusion. Ischaemia decreased left ventricular developed pressure to 18 ± 11 % (1.1) and 50 ± 11 % (2.1) of initial value (mean ± SEM) at the start of reperfusion. Left ventricular end-diastolic pressure increased from 0 to 79 ± 8 mmHg (1.1) and 39 ± 9 (2.1) mmHg, while left ventricular systolic pressure was unchanged (101 ± 12% in 1.1 and 101 ± 10% in 2.1). Severe arrhythmias were induced in 90 (1.1) and 30 (2.1)% of the hearts, while coronary flow decreased during reperfusion. H₂-blockade did not modify the changes in left ventricular pressures, coronary flow, or heart rate induced by ischaemia. Three different Hj-blockers increased left ventricular systolic pressure, inhibited the decrease of developed pressure, attenuated the increase of end-diastolic pressure, and totally inhibited reperfusion arrhythmias. The effect of both blockers together was similar to that of H₁-blockers alone. Coronary flow was increased during reperfusion in two of the groups with Hj-blocker compared with ischaemic controls. Increased release of histamine from ischaemic-reperfused rat hearts concurred with depression of left ventricular function and arrhythmias during early reperfusion. Cardiac dysfunction during reperfusion was attenuated by three different Hj-receptor blockers.