慢性压力超负荷左室电重构的异质性及离子基础

目的研究慢性压力超负荷左室电重构的异质性及离子基础。方法新西兰兔通过肾上腹主动脉次全结扎诱发左室慢性压力超负荷。采用全细胞膜片钳技术分别记录对照组及手术组左室内膜、中层及外膜细胞的动作电位，慢激活的延迟整流钾电流（IKs）及快激活的延迟整流钾电流（IKr）等。结果与对照组比较，基础周长为2S时，手术组左室内膜、中层及外膜细胞的动作电位复极90％的时程（APD90）分别延长27．7％、27．2％（P〈0．05或0．01）、19．6％（P〉0．05）；对照组中层细胞的APD90较外膜细胞长50．8％，而手术组为60．4％；在测试电位为＋50mV时，手术组左室内膜、中层及外膜细胞IKs尾电流密度分别减小26．1％、36．3％（P均〈0．05）、23．0％（P〉0．05）；IKr尾电流密度分别减小31．7％、30．5％、30．0％（P〈0．01或0．05）。对照组外膜细胞的IKs尾电流密度较中层细胞大49．1％，而手术组为77．6％；两组三层细胞之间IKr尾电流密度均无差别。结论正常兔左室存在跨壁复极异质性，心肌肥厚时进一步扩大，IKs分布及下调的不均一性是其离子流基础。     

左心室肥厚跨室壁电不均一性及缬沙坦对其影响的实验研究

目的 :探讨肥厚心肌跨室壁复极不均一性及缬沙坦预防性给药的影响。方法 :家兔 30只 ,随机分为 3组 ,腹主动脉缩窄组 (缩窄组 )、假手术组、用药组。主动脉缩窄术制备家兔高血压心肌肥厚模型 ,胶原两步消化法分离获取左心室内膜、中层及外膜单个心肌细胞 ,以全细胞膜片钳技术记录单细胞跨膜动作电位和离子流。结果 :腹主动脉缩窄组外膜、中层、内膜 3层心肌细胞跨膜动作电位复极达 90 %时程 (APD90 )均较假手术组及用药组延长 ,有显著性差异 (P <0 0 5～ 0 0 1)。以中层心肌细胞延长最为明显 (延长比例 :中层 2 3% ,外膜 10 % ,内膜 8% ) ,使肥厚心肌跨室壁复极不均一性明显增大。用药组与假手术组间各层细胞跨膜动作电位复极达 90 %时程均无明显差异。缩窄组各层心肌细胞瞬时外向钾电流 (Ito)和延迟整流钾电流 (Iks)密度均较用药组及假手术组下降 ,有显著性差异 (P <0 0 5 ) ,以中层细胞下降的幅度最大 ,而用药组及假手术组间心肌细胞瞬时外向钾电流、延迟整流钾电流密度无显著差异。结论 :家兔心肌肥厚时中层心肌细胞跨膜动作电位复极达 90 %时程延长及心肌细胞瞬时外向钾电流、延迟整流钾电流下降较外膜和内膜细胞更为明显 ,使肥厚心肌跨室壁复极不均一性增大。缬沙坦预防性给药可抑制这一变化 ,     

胰岛素对家兔右室心肌各层细胞动作电位的影响

目的探讨不同浓度胰岛素对右室三层细胞即内膜下、中膜、外膜下细胞动作电位(AP)的影响。方法采用酶解法分离右室三层心肌细胞,膜片钳技术记录右室三层细胞的AP,分别予40,280,600,2 400,4 000 pmol/L胰岛素干预后记录动作电位振幅(APA)、完成动作电位复极20%、50%、90%的时间即APD20、APD50、APD90并进行比较。结果①40 pmol/L胰岛素对右室外膜下、中膜细胞APD无明显影响;280,600,2 400,4 000 pmol/L胰岛素显著缩短右室外膜下、中膜细胞APD。②40,280,600 pmol/L胰岛素对右室内膜下细胞APD无明显影响;2 400,4000 pmol/L胰岛素显著缩短右室内膜下细胞APD。③4 000 pmol/L胰岛素使右室外膜下、中膜细胞APA辐值显著减小。结论胰岛素对右室内外膜心肌细胞的AP呈现不一致的作用,增大了跨膜动作电位梯度,可能与心律失常的发生有关。     

低渗性肿胀对豚鼠心室肌细胞动作电位及延迟整流钾电流的影响

观察单个豚鼠心室肌细胞动作电位和主要复极期电流延迟整流钾电流(IK)的变化,探讨急性心肌缺血再灌注室性心律失常发生的离子机制。采用全细胞膜片钳记录技术,观察低渗液(200mOsm/kg)灌流胶原酶分离的单个豚鼠心室肌细胞发生肿胀后的动作电位各参数的变化,同时记录IK及其快、慢两种激活成分(IKr及IKs)的变化。结果:低渗液灌流后心室肌细胞迅速发生肿胀,动作电位幅度(APA)、静息膜电位(RMP)及阈电位水平无明显变化;而动作电位时程(APD)在600,1000和3000ms三种基础起搏周长(BCL)刺激时均缩短(P<0.05),尤以APD复极达50%和90%时缩短更为明显。APD生理性频率适应性消失且离散度增大。低渗性肿胀状态下IK电流幅度在3000ms长去极化保持时间(主要成分为IKs)刺激时从1134.33±150.17pA增加至1621.98±234.95pA(P<0.001,n=10);而在100ms短去极化保持时间(主要成分为IKr)刺激时从693.44±96.44pA降低至294.06±71.79pA(P<0.05,n=8);并且使IK的IV曲线向上移位。结论:低渗性肿胀的心室肌细胞IK特别是IKs的增加是引起APD缩短的重要因素,是急性心肌缺血再灌注室性心律失常发生的离子机制之一。     

慢性压力超负荷兔左室心肌细胞电重构与结构重构发生的非同步性

目的探讨慢性压力超负荷兔中层心室肌细胞电重构与结构重构发生的非同步性及其意义。方法新西兰兔64只,随机分为缩窄组和假手术组,采用肾上腹主动脉缩窄术制备兔左室压力超负荷模型。术后2周和8周胶原酶两步消化法分离获取左室中层单个心肌细胞,应用激光扫描共聚焦显微镜技术测定中层细胞体积和蛋白含量,全细胞膜片钳技术记录中层细胞膜电容、动作电位(AP)。结果与假手术组比较,术后2周缩窄组中层细胞体积、蛋白含量及膜电容无明显改变,但基础刺激周长(BCL)为2 s时,缩窄组AP复极达90%时程(APD90)较假手术组延长13.7%(P<0.05);与假手术组比较,术后8周缩窄组中层细胞体积、蛋白含量及膜电容分别增加28.0%、38.3%、34.0%(P<0.05或0.01),APD90延长30.6%(P<0.01)。术后2周和8周,与假手术组比较,缩窄组中层细胞APD呈现更明显的频率依赖性,且更易发生早期后除极(BCL=2 s,EAD)。结论左室慢性压力超负荷过程中,中层心肌细胞电重构的发生明显早于结构重构,且可能具有潜在致心律失常危险。     

左室肥厚单个心肌细胞三层跨膜动作电位的不均一性改变

为探讨兔左室肥厚心肌内膜下、中层及外膜下单个细胞跨膜动作电位 (AP)的不均一性改变。将实验兔分为手术组和假手术组。手术组行腹主动脉缩窄术制备心肌肥厚模型 ,假手术组仅分离暴露腹主动脉而不缩窄。按胶元酶二步消化法分离兔心室肌细胞 ,其中用剃须刀分离左室游离壁内、中、外三层心肌。采用全细胞膜片钳记录AP。结果 :手术组三层心肌细胞AP复极达 90 %的时程 (APD90 ) (内膜下 :181± 18ms,中层 :2 4 6± 2 1ms,外膜下 :196± 15ms)较假手术组均明显延长 (内膜下 :14 2± 13ms,中层 :182± 15ms,外膜下 :15 8± 16ms,n =13,P <0 .0 1～ 0 .0 5 ) ,且以中层心肌细胞延长比例最大。手术组早期后除极的发生率明显大于假手术组 (6 0 %vs 10 % ,n =10 ,P <0 .0 0 1)。结论 :兔左室肥厚三层心肌细胞间的跨室壁复极不均一性明显增大。     

盐酸关附甲素对豚鼠和大鼠心肌细胞钾通道的阻断作用

目的用膜片钳全细胞记录法观察盐酸关附甲素(GFA)对分离的单个豚鼠心室肌细胞缓慢激活型延迟整流钾电流(IKs),大鼠内向整流钾电流(IK1)、瞬时外向钾电流(Ito)的影响。方法用急性酶解法分离获得单个豚鼠和大鼠心室肌细胞。用标准的全细胞膜片钳技术记录IKs、IK1、Ito离子通道电流,观察不同浓度的GFA对豚鼠心室肌细胞IKs,大鼠心室肌细胞IK1、Ito的影响。结果50,150,500μmol/LGFA使IKs尾电流(IKs,tail)最大峰值电流密度分别降低11.4%±3.32%、23.3%±7.36%、36.7%±4.99%,P<0.05;使IK1稳态电流密度分别降低5.1%±0.6%、7.5%±0.9%、7.2%±0.9%;50,500μmol/LGFA使Ito最大峰值电流密度分别降低6.1%±0.64%、8.6%±1.13%。结论GFA对IKs具有浓度依赖性阻滞作用,这可能是其延长动作电位时程而对静息电位影响不大的电生理基础,是其抗心律失常作用的机制之一。     

1-磷酸鞘氨醇对心肌细胞延迟整流钾电流2种成分的作用

目的:研究1-磷酸鞘氨醇(S1P)对豚鼠心室肌细胞延迟整流钾电流的2种成分快速激活整流钾电流(IKr)和缓慢激活整流钾电流(IKs)的作用。方法:用胶原酶酶解法急性分离豚鼠心室肌细胞,随机分为正常对照组、S1P(1.1μmol/L)组、S1P(1.1μmol/L)加苏拉明(Suramin)(200μmol/L)组。利用全细胞膜片钳的方法记录心室肌细胞IKr和IKs及其尾电流。结果:①对照组IKr和IKr的尾电流分别为(0.85±0.53)nA和(0.65±0.40)nA。加入S1P后,IKr和IKr的尾电流受到明显抑制,下降到(0.63±0.37)nA和(0.56±0.29)nA(P<0.05,n=6)。而加入S1P加Suramin后,抑制作用消失,IKr和IKr的尾电流为(0.85±0.41)nA和(0.71±0.43)nA,与对照组相比差异无统计学意义(P>0.05,n=6)。②对照组IKs和IKs的尾电流分别为(1.53±0.61)nA和(0.82±0.34)nA。加入S1P后,下降到(1.47±0.46)nA和(0.79±0.41)nA,但差异无统计学意义(P>0.05,n=6)。结论:S1P可降低豚鼠心室肌细胞IKr的幅值,并且是通过其特异性的G蛋白耦联S1P受体介导而产生这些作用。S1P对豚鼠心室肌细胞IKs没有作用。     

异丙酚对家兔心室外膜心肌细胞动作电位和L-型钙电流的影响

目的研究异丙酚对家兔左、右心室心外膜心肌细胞动作电位和L-型钙电流的影响。方法酶解法分离家兔左、右心室心外膜心肌细胞。全细胞膜片钳技术记录左、右心室心外膜心肌细胞动作电位和L-型钙电流(ICa-L)在使用异丙酚前后的变化。结果在电流钳制下,左、右心室心外膜心肌细胞动作电位都具有从0期到4期的动作电位形态,2相平台期有心外膜心肌细胞特有的穹窿样突起。异丙酚使右室心外膜心肌细胞动作电位失去2相平台期穹窿样突起,呈三角形尖锥锋形。左、右心室心外膜心肌细胞动作电位时程复极化50%和90%(APD50和APD90)在异丙酚作用后都明显缩短,其中右室心外膜心肌细胞APD50和APD90缩短最为明显(P<0.05或0.01)。在电压钳制下,异丙酚使左、右心室心外膜心肌细胞ICa-L在同一指令电位下,电流幅度均明显减小,但右室心外膜心肌细胞ICa-L的减小幅度明显强于左室同层ICa-L的减小幅度(P<0.01)。异丙酚还使左、右心室心外膜心肌细胞ICa-L的I-V曲线上移,并且使右室心外膜心肌细胞ICa-L的I-V曲线处在所有I-V曲线最上部。结论异丙酚对右室心外膜心肌细胞动作电位和ICa-L的影响程度明显强于左室,从而引起左、右心外膜心肌细胞电不均一性。     

酚噻嗪对豚鼠心室肌细胞动作电位时程和跨膜离子电流作用的研究

通过观察酚噻嗪对豚鼠单心室肌细胞动作电位时程 (APD)及动作电位形成过程中主要离子通道的作用 ,探讨其诱发长QT间期 (LQT)综合征及室性心律失常的可能机制。采用膜片钳技术中的Nystatin 破膜法观察酚噻嗪对豚鼠心室肌细胞APD的作用 ,采用全细胞技术研究酚噻嗪对心室肌细胞动作电位形成过程中主要离子电流的作用。结果 :①在 5Hz剌激频率时 ,10 0 μmol/L酚噻嗪使APD90 延长 2 5 .8%± 3.8% (n =10 ,P <0 .0 1) ,作用呈部分可逆性 ;②在分别持续 2 5 0ms和 10 0 0ms至不同膜电位水平去极化的实验中 ,酚噻嗪对延迟整流钾电流 (IK)尾电流有明显的抑制作用 ,在 +6 0mV持续 2 5 0ms的去极化时 ,5 0 .6 4 %± 6 .4 6 %的IK尾电流受抑制 (n =7,P <0 .0 5 ) ,这一抑制作用呈浓度依赖性 ,半抑制浓度 (IC50 ) =2 5 .98μmol/L ,Hill常数为 0 .75。当采用IK快速激活成分 (IKr)的特异性阻断剂E 4 0 31阻断IKr后 ,酚噻嗪对IK尾电流的阻断作用消失。 30 0 μmol/L酚噻嗪对IKr的抑制作用仍弱于 0 .5mmol/LE 4 0 31。在 10 0 0ms,至 +2 0mV去极化的情况下 ,酚噻嗪对IK尾电流的IC50 为 2 5 .98μmol/L ,这一抑制作用可部分洗脱。受酚噻嗪抑制的电流与IK中IKr具有相似的通道动力学特性 ;③未发现酚噻嗪对IK稳态电流、IK?     

Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents.

OBJECTIVE: To elucidate the regional difference of the K+ current blocking effects of methanesulfonanilide class III agents. METHODS: Regional differences in action potential duration (APD) and E-4031-sensitive component (IKr) as well as -insensitive component (IKs) of the delayed rectifier K+ current (IK) were investigated in enzymatically isolated myocytes from apical and basal regions of the rabbit left ventricle using the whole-cell clamp technique. RESULTS: At 1 Hz stimulation, APD was significantly longer in the apex than in the base (223.1 +/- 10.6 vs. 182.7 +/- 14.5 ms, p < 0.05); application of 1 microM E-4031 caused more significant APD prolongation in the apex than in the base (32.5 +/- 6.4% vs. 21.0 +/- 8.8%, p < 0.05), resulting in an augmentation of regional dispersion of APD. In response to a 3-s depolarization pulse to +40 mV from a holding potential of -50 mV, both IK tail and IKs tail densities were significantly smaller in apical than in basal myocytes (IK: 1.56 +/- 0.13 vs. 2.09 +/- 0.21 pA/pF, p < 0.05; IKs: 0.40 +/- 0.15 vs. 1.43 +/- 0.23, p < 0.01), whereas IKr tail density was significantly greater in the apex than in the base (1.15 +/- 0.13 vs. 0.66 +/- 0.11 pA/pF, p < 0.01). The ratio of IKs/IKr for the tail current in the apex was significantly smaller than that in the base (0.51 +/- 0.21 vs. 3.09 +/- 0.89; p < 0.05). No statistical difference was observed in the voltage dependence as well as activation and deactivation kinetics of IKr and IKs between the apex and base. Isoproterenol (1 microM) increased the time-dependent outward current of IKs by 111 +/- 8% during the 3-s depolarizing step at +40 mV and its tail current by 120 +/- 9% on repolarization to the holding potential of -50 mV, whereas it did not affect IKr. CONCLUSIONS: The regional differences in IK, in particular differences in its two components may underlie the regional disparity in APD, and that methanesulfonanilide class III antiarrhythmic agents such as E-4031 may cause a greater spatial inhomogeneity of ventricular repolarization, leading to re-entrant arrhythmias.     

Delayed rectifier potassium current in undiseased human ventricular myocytes

OBJECTIVE: The purpose of the study was to investigate the properties of the delayed rectifier potassium current (IK) in myocytes isolated from undiseased human left ventricles. METHODS: The whole-cell configuration of the patch-clamp technique was applied in 28 left ventricular myocytes from 13 hearts at 35 degrees C. RESULTS: An E-4031 sensitive tail current identified the rapid component of IK (IKr) in the myocytes, but there was no evidence for an E-4031 insensitive slow component of IK (IKs). When nifedipine (5 microM) was used to block the inward calcium current (ICa), IKr activation was fast (tau = 31.0 +/- 7.4 ms, at +30 mV, n = 5) and deactivation kinetics were biexponential and relatively slow (tau 1 = 600.0 +/- 53.9 ms and tau 2 = 6792.2 +/- 875.7 ms, at -40 mV, n = 7). Application of CdCl2 (250 microM) to block ICa altered the voltage dependence of the IKr considerably, slowing its activation (tau = 657.1 +/- 109.1 ms, at +30 mV, n = 5) and accelerating its deactivation (tau = 104.0 +/- 18.5 ms, at -40 mV, n = 8). CONCLUSIONS: In undiseased human ventricle at 35 degrees C IKr exists having fast activation and slow deactivation kinetics; however, there was no evidence found for an expressed IKs. IKr probably plays an important role in the frequency dependent modulation of repolarization in undiseased human ventricle, and is a target for many Class III antiarrhythmic drugs.     

芍药苷对心脏钾通道电生理功能的影响

目的研究芍药苷对内向整流钾电流(IK1)、瞬时外向钾电流(Ito)以及延迟整流钾电流(IKs和IKr)的作用。方法用全细胞膜片钳技术记录大鼠心室肌细胞的Ito和IK1电流。而IKs和IKr电流在转染相应质粒的HEK293细胞上记录。对比芍药苷使用前后的电流图,观察芍药苷对各种离子通道电流的影响。结果在-100mV测试电压下,100μmol/L的芍药苷能使IK1峰值密度从(-25.26±8.21)pA/pF降至(-17.65±6.52)pA/pF,平均抑制率为30.13%(n=6,P<0.05),但对其反转电位以及内向整流特性无影响。此外,100μmol/L芍药苷对Ito、IKs和IKr电流无明显作用。结论芍药苷对IK1电流具有明显的抑制作用,而对Ito、IKs及IKr无明显作用。     

Differential effects of the transient outward K current activator NS5806 in the canine left ventricle

To examine the electrophysiological and molecular properties of the transient outward current (I_to) in canine left ventricle using a novel I_to activator, NS5806, I_to was measured in isolated epicardial (Epi), midmyocardial (Mid) and endocardial (Endo) cells using whole-cell patch-clamp techniques. NS5806 activation of K_v4.3 current was also studied in CHO-K1 cells and Xenopus laevis oocytes. In CHO-K1 cells co-transfected with K_v4.3 and KChIP2, NS5806 (10 μM) caused a 35% increase in current amplitude and a marked slowing of current decay with τ increasing from 7.0 ± 0.4 to 10.2 ± 0.3 ms. In the absence of KChIP2, current decay was unaffected by NS5806. In ventricular myocytes, NS5806 increased I_to density by 80%, 82%, and 16% in Epi, Mid, and Endo myocytes, respectively (at + 40 mV) and shifted steady-state inactivation to negative potentials. NS5806 also significantly slowed decay of I_to, increasing total charge to 227%, 192% and 83% of control in Epi, Mid and Endo cells, respectively (+ 40 mV, p < 0.05). Quantification of K_v4.3 and KChIP2 mRNA in the 3 ventricular cell types revealed that levels of K_v4.3 message was uniform but those of KChIP2 were significantly greater in Epi and Mid cells. The KChIP2 gradient was confirmed at the protein level by Western blot. Our results suggest that NS5806 augments I_to by increasing current density and slowing decay and that both depend on the presence of KChIP2. I_to and its augmentation by NS5806 are greatest in Epi and Mid cells because KChIP2 levels are highest in these cell types.     

自主神经系统对在体犬跨室壁三层心肌不应期不均一性影响的研究

为探讨自主神经系统对在体犬跨室壁三层心肌细胞不应期离散度的影响 ,分别在基础和缺血状态下 ,在交感神经和迷走神经刺激的过程中 ,用程序刺激法测定健康家犬在体心外膜心肌、中层心肌和心内膜心肌的不应期。结果 :在基础状态下 ,交感神经刺激能缩短三层心肌细胞的不应期 ,中层心肌细胞的不应期缩短最明显 ,跨室壁三层心肌不应期的离散度由 3± 2ms增加到 18± 6ms(P <0 .0 1) ;迷走神经刺激能延长三层心肌的不应期 ,心内膜心肌增加明显 ,跨室壁不应期离散度由 3± 2ms增加到 9± 4ms(P <0 .0 5 )。在急性缺血状态下 ,交感神经刺激延长三层心肌细胞的不应期 ,其中中层心肌细胞的不应期增加最明显 ,与刺激前相比 ,跨室壁不应期离散度由 4± 3ms增加到 16± 4ms(P <0 .0 1) ;迷走神经刺激对三层心肌细胞的不应期影响较小 ,与刺激前相比 ,跨室壁不应期离散度无显著变化。结论 :在基础及缺血状态下 ,交感神经刺激均能增加跨室壁不应期离散度 ;迷走神经刺激对跨室壁不应期离散度无显著影响。     

兔肥厚心肌慢反应延迟整流钾通道表达的变化

目的:慢反应延迟整流钾通道(IKs)是心肌细胞复极的重要组成部分,本实验观察左心室肥厚对心外膜下心肌(Epi)和心内膜下心肌(Endo)IKs的mRNA表达水平变化。方法:家兔16只随机分为假手术组和心肌肥厚组。心肌肥厚组通过部分结扎腹主动脉的方法造成兔压力负荷性心肌肥厚模型,假手术组只暴露腹主动脉而不行缩窄术。应用RT-PCR技术检测IKs通道基因KvLQT1(α亚单位)和minK(β亚单位)的mRNA表达。结果:假手术组EpiIKs通道α亚单位基因KvLQT1为Endo的2.5倍,EpiIKs通道β亚单位基因minK为Endo的3.3倍。与假手术组相比,心肌肥厚组Epi和EndoIKs通道α亚单位基因KvLQT1表达分别降低40%和25%,心肌肥厚组Epi和EndoIKs通道β亚单位基因minK表达分别降低50%和33%。结论:IKs通道基因KvLQT1和minK的mRNA表达存在跨室壁的差异。心肌肥厚可造成Epi和EndoIKs的mRNA表达不均一的下降。     

Repolarizing K+ currents ITO1 and IKs are larger in right than left canine ventricular midmyocardium

BACKGROUND: The ventricular action potential exhibits regional heterogeneity in configuration and duration (APD). Across the left ventricular (LV) free wall, this is explained by differences in repolarizing K+ currents. However, the ionic basis of electrical nonuniformity in the right ventricle (RV) versus the LV is poorly investigated. We examined transient outward (ITO1), delayed (IKs and IKr), and inward rectifier K+ currents (IK1) in relation to action potential characteristics of RV and LV midmyocardial (M) cells of the same adult canine hearts. METHODS AND RESULTS: Single RV and LV M cells were used for microelectrode recordings and whole-cell voltage clamping. Action potentials showed deeper notches, shorter APDs at 50% and 95% of repolarization, and less prolongation on slowing of the pacing rate in RV than LV. ITO1 density was significantly larger in RV than LV, whereas steady-state inactivation and rate of recovery were similar. IKs tail currents, measured at -25 mV and insensitive to almokalant (2 micromol/L), were considerably larger in RV than LV. IKr, measured as almokalant-sensitive tail currents at -50 mV, and IK1 were not different in the 2 ventricles. CONCLUSIONS: Differences in K+ currents may well explain the interventricular heterogeneity of action potentials in M layers of the canine heart. These results contribute to a further phenotyping of the ventricular action potential under physiological conditions.     

腺苷对心肌梗死兔非梗死区心室细胞快钠通道跨壁异质性的影响及其离子机制

目的 探讨腺苷（Ado）对急性心肌梗死（AMI）后非梗死区心肌细胞快钠通道电流（INa）跨壁异质性的影响.方法 36只兔随机分为4组,其中两组建立AMI动物模型,分别为Ado组和MI组,其余两组为正常对照组和假手术对照组.1个月后,用膜片钳技术研究左室非梗死区3层心肌细胞INa的改变.结果 正常对照组左室3层细胞的钠电流存在异质性,中层心肌（M）细胞的峰值INa是心内膜层（Endo）和心外膜层（Epi）的2倍多;M细胞的INa失活最快;对照组与假手术组无明显差别.MI组3层细胞的INa电流密度下降,以M细胞变化最显著,INa稳态失活曲线均左移,以Epi变化最显著;Ado组3层细胞INa电流密度下降显著,稳态失活曲线左移最明显并趋向一致,失活后恢复曲线均恢复减慢.结论 左室心肌细胞的INa存在跨壁异质性;AMI对INa的跨壁异质性有明显影响;而Ado减弱AMI后INa的跨壁异质性.     

急性缺血对犬在体心肌跨心室壁复极不均一性的影响

目的：探讨急性缺血对犬在体心肌跨心室壁复极不均一性及与心律失常的关系。方法：健康家犬10只，应用单相动作电位记录技术，同步记录健康家犬在体阻断左前降支主干前后心外膜、中层及心内膜心肌单相动作电位及体表心电图，分析相关参数的变化。结果：3层心肌单相动作电位时程正常供血状态下差异无显著性意义（P＞0．05），急性缺血状态下则均明显缩短，且心外膜、心内膜的缩短程度较中层心肌更为明显，差异有显著性意义（P＜0．05）。3层心肌间跨室壁复极离散度增大。10只犬中正常供血状态下无一例出现心律失常，急性缺血30min内4只出现了室性心动过速或心室颤动死亡，恶性心律失常发生率达40％。结论：急性缺血时犬在体心肌跨心室壁复极离散度增大，可能是导致缺血性室性心律失常的原因之一。     

陈旧性心肌梗死对家兔动作电位时程跨室壁离散及L型钙电流的影响

探讨陈旧性心肌梗死 (MI) (MI后 3个月 ) ,远离MI中心区的心肌细胞电活动的改变。结扎家兔左前降支造成MI模型 ,3个月后酶解分离左室游离壁远离MI中心区的三层 (Epi、M、Endo)心肌细胞 ,采用全细胞膜片钳技术记录单细胞动作电位 (AP)和L型钙电流 (ICa ,L) ,并观察三层心肌细胞AP时程 (APD)的离散性 (TD APD)变化。结果 :MI后 3个月 ,远离MI区的三层心肌细胞的APD明显延长 ,其中Endo心肌细胞的APD明显短于Epi和M心肌细胞(P <0 .0 1)。陈旧性MI组 (OMI)与假手术组 (Sham)及对照组 (Control)比较 ,TD APD显著增加 (2 88.32± 19.5 6vs2 2 8.4 5± 13.94 ,2 10 .32± 17.4 3ms ,P <0 .0 1)。且在OMI组 ,ICa ,L的幅值增加 ,但密度降低 ,其中Endo的ICa,L密度降低最明显 (+10mV时 ,从 16 .12± 1.6 0降至 10 .73± 0 .0 6pA/pF ,降低了 33.4 3% ,Epi从 16 .5 9± 0 .5 0降至 11.75±0 .6 9pA/pF ,降低了 2 9.17% ,M细胞从 18.70± 1.0 3降至 13.2 7± 1.0 5pA/pF ,降低了 2 9.0 3% ,P <0 .0 5 )。结论 :MI3个月后远离MI区的心肌细胞ICa ,L密度明显降低 ,且以Endo降低最明显 ,三层心肌细胞的APD明显延长 ,并且En do心肌细胞的APD明显短于Epi和M心肌细胞 ,TD APD明显增加