腺苷抗豚鼠室性心律失常的电生理研究

实验用全细胞膜片钳技术在单个豚鼠心室肌细胞上研究了腺苷 (Ado)对正常及异丙肾上腺素 (Iso)致豚鼠心室肌细胞动作电位、迟后除极 (DAD)、L 型钙电流 (ICa.L)和短暂内向电流 (Iti)的作用。结果表明 :(1)Ado在2 0～ 10 0 μmol/L时对豚鼠心室肌细胞动作电位和ICa .L无明显直接作用 ,但却可明显降低Iso所致的动作电位时程(APD)延长和ICa .L峰值增大 ,Iso (10nmol/L)使细胞APD50 从 3 40± 2 1ms延长到 486± 2 8ms (P <0 0 1) ,APD90从 3 61± 17ms延长至 5 0 1± 2 9ms (P <0 0 1) ;ICa .L峰值从 - 6 5 3± 1 4pA/pF增大到 - 18 2 8± 2 4pA/pF (P <0 0 1) ,电流电压曲线明显左移和下移 ;Ado (5 0 μmol/L)使APD50 和APD90 降至 40 3± 19ms和 419± 2 6ms ,但并不影响动作电位其它参数 ,使ICa.L峰值降低至 - 10 2± 1 5pA/pF (P <0 0 1)。 (2 )Iso (3 0nmol/L)可诱发心室肌细胞产生DADs,其发生率为 10 0 % ;Ado (5 0 μmol/L)可完全抑制Iso引发DADs;细胞经 - 40～ +2 0mV、时程 2s的除极电压 ,Iso (3 0nmol/L)诱导出Iti,其发生率为 10 0 % ;Ado (5 0 μmol/L)可明显抑制Iso致Iti的发生 ,其发生率降为 14 3 %。研究结果提示 ,Ado对豚鼠心室肌细胞动作电位和ICa.L无明显直接作用 ,但却可显著降低Is     

不饱和脂肪酸在低渗牵张加强豚鼠胃窦平滑肌细胞毒蕈碱电流中的作用

利用全细胞膜片钳技术在急性分离的胃窦平滑肌细胞上记录离子电流的方法 ,探讨外源性不饱和脂肪酸是否参与低渗牵张加强毒蕈碱电流的过程。在豚鼠胃窦平滑肌细胞上膜电位被钳制在 - 2 0 0mV等渗状态时 ,5 0 μmol/L卡巴胆碱 (carbachol,CCh)引起的毒蕈碱电流 (ICCh)作为对照 ,发现低渗牵张可以使ICCh明显增加到对照的 2 2 6 0±2 1 0 %。当用含 5 μmol花生四烯酸 (arachidacid ,AA)、亚麻酸 (linoleicacid ,LA)或亚油酸 (oleicacid,OA)细胞外液灌流时 ,ICCh分别被抑制在对照的 3 8± 0 6%、3 5 2± 0 8%和 66 6± 0 6%。在这种情况下 ,低渗牵张刺激可以使ICCh分别增加到 10 6 0± 2 5 %、173 2± 6 8%和 2 2 2 1± 11 0 %。 5 μmol/LAA抑制低渗牵张增加的毒蕈碱电流 5 1 2± 3 8% ,而在等渗状态下抑制ICCh为 96 2± 1 6%。上述结果提示 ,不饱和脂肪酸中双键数目越多 ,抑制效应越强 ;但不饱和脂肪酸不参与低渗刺激加强毒蕈碱电流的过程。     

微丝在低渗牵张诱导毒蕈碱电流增加中的作用

在急性分离的豚鼠胃窦平滑肌细胞上 ,利用膜片钳技术的传统全细胞模式记录离子电流的方法 ,探讨微丝在低渗牵张诱导毒蕈碱电流增加中的作用。当豚鼠胃窦平滑肌细胞的膜电位钳制在 - 2 0mV时 ,灌流液中 5 0μmol/L 卡巴胆碱 (carbachol,CCh)或电极内液中 0 5mmol/LGTPγS均可引导毒蕈碱电流 (muscariniccurrentICCh) ,低渗牵张 ( 2 0 2mOsmol/L)分别使其增加 145± 2 7%和 183± 3 0 % ;当电极内液中加入 2 0 μmol/L的细胞松弛B (一种微丝骨架的解聚剂 )时 ,低渗牵张使ICCh只增加 70± 6% ;而电极内液中加入 2 0 μmol/L的鬼笔环肽 (一种微丝骨架的稳定剂 )则使ICCh增加了 5 45± 81%。结果表明 ,低渗牵张可增加由卡巴胆碱或GTPγS诱导的毒蕈碱电流 ,微丝参与调节低渗牵张诱导豚鼠胃窦平滑肌细胞ICCh增加的作用     

自发性高血压大鼠和Wistar-Kyoto大鼠心血管组织肾上腺髓质素和肾上腺髓质素原N-末端20肽的水平

本工作观察了自发性高血压大鼠 (SHRs)和Wistar kyoto (WKY)大鼠心肌和主动脉肾上腺髓质素 (a drenomedullin ,ADM)和肾上腺髓质素原N 末端 2 0肽 (proadrenomedullinNterminal 2 0peptide ,PAMP)的水平。以放射免疫分析方法测定血浆、心肌和主动脉ADM含量。用竞争性定量逆转录多聚酶链式反应 (RT PCR)方法测定心肌和主动脉ProADMmRNA含量。结果发现 ,SHRs心肌和主动脉ProADMmRNA水平分别比WKY大鼠高 66 7%和 73 % (均P <0 0 1)。SHRs血浆、心肌和主动脉ADM ir含量分别较WKY大鼠高 2 9%、76 7%和 79% (均P <0 0 1)。SHRs血浆、心肌和主动脉PAMP ir水平分别较WKY大鼠高 42 5 % (P <0 0 1)、47 2 % (P <0 0 1)和 2 7 3 % (P <0 0 5 )。另外 ,SHRs的ADM和PAMP的比值较WKY大鼠明显增高 (心肌和主动脉分别为 2 0± 0 2 5vs 1 64± 0 3和 2 2± 0 18vs 1 5 6± 0 2 8)。结果提示 ,SHRs心肌和主动脉ProADM基因表达上调 ,ADM和PAMP水平升高 ,但二者升高的比例不一致。SHRs的ADM和PAMP升高不一致的病理生理意义有待进一步研究     

心室不同部位起搏对正常犬和扩张型心肌病心力衰竭犬模型在体心肌跨室壁复极离散的影响

实验以正常犬和扩张型心肌病心力衰竭犬(dilated cardiomyopathy congestive heart failure,DCM-CHF)模型为对象、以心肌跨室壁复极离散的相关参数为指标,研究左心室心外膜起搏、双心室起搏(模拟临床上心室再同步治疗的方法)后的心肌电生理特性变化。实验以快速右心室起搏的方法制备DCM-CHF犬模型;正常犬和DCM-CHF犬均经射频消融希氏束制备三度房室传导阻滞模型;采用同步记录犬体表心电图和内膜下、中层、外膜下三层心肌单相动作电位(monophasic action potentials,MAP)的方法,测定不同部位起搏时的QT间期、Tpeak-Tend(Tp-Te)间期和三层心肌的单相动作电位时程(MAP duration,MAPD)、跨室壁复极离散度(transmural dispersion of repolaization,TDR)。结果显示:在正常犬,左室心外膜与双心室起搏后三层心肌的MAPD均延长,同时TDR增大(左室心外膜起搏47.16 ms、双心室起搏37.54 ms、右室心内膜起搏26.75 ms,P<0.001),体表心电图Tp-Te间期的变化与之平行;在DCM-CHF犬较正常犬已表现出中层心肌MAPD延长(276.30 ms vs 257.35 ms,P<0.0001)和TDR(33.8 ms vs 27.58 ms,P=0.002)增大的基础上,左室心外膜参与起搏后仍进一步使三层心肌的MAPD延长和TDR增大。研究结果提示,左室心外膜起搏和双心室起搏后使内膜下、中层     

链霉素对颈动脉窦压力感受器反射的抑制作用

在 2 3只隔离灌流颈动脉窦区的麻醉大鼠 ,观察了链霉素对颈动脉窦压力感受器反射的影响。结果如下 :(1)以链霉素 (10 0 μmol/L)隔离灌流大鼠左侧颈动脉窦区时 ,压力感受器反射机能曲线向左下方移位 ,曲线最大斜率 (PS)由 0 40± 0 0 1kPa降至 0 33± 0 0 1kPa (P <0 0 0 1) ,血压反射性下降 (reflexdecrease ,RD)幅度由 6 2 2±0 13kPa降至 5 0 2± 0 11kPa (P <0 0 0 1) ,阈压 (TP)、平衡压 (EP)和饱和压 (SP)则分别从 8 2 7± 0 2 5 ,12 71± 0 2 1和 2 4 41± 0 14kPa增至 10 33± 0 32 (P <0 0 1) ,13 33± 0 30 (P <0 0 1)和 2 6 11± 0 2 8kPa (P <0 0 1)。其中RD ,PS和TP的变化呈明显的剂量依赖性。 (2 )应用腺苷隔离灌流大鼠颈动脉窦区 ,引起颈动脉窦压力感受器反射的易化 ;在用链霉素预处理后 ,此易化效应不仅完全被阻断 ,且可使反射效应小于应用腺苷前的对照值。以上结果表明 ,链霉素对大鼠颈动脉窦压力感受器反射有明显的抑制作用。     

细胞外pH值降低可增强豚鼠心室肌细胞持续性钠电流

应用全细胞和单通道(贴附式)膜片钳技术观察胞外pH值降低对心室肌细胞持续性钠电流(persistent sodium current,ⅠNa.P)的影响,探讨其作用机制。结果显示:全细胞记录模式下,细胞外pH值降低可明显增大ⅠNa.P,且呈H+浓度依赖性增强。当细胞外pH值从对照值的7．4降低为6．5时,ⅠNa.P的电流密度从(0．347±0．067)pAJpF增加到(0．817±0．137)pA/pF(P< 0．01,n=6),而加入还原剂1,4-二硫甙苏糖醇(dithiothreitiol,DTT,1 mmol／L)后可使,ⅠNa.P的电流密度回落到(0．233±0．078)pA／pF (P<0．01 vs pH 6．5,n=6)。单通道记录模式中,当细胞外pH值从对照值的7．4降低为6．5时,持续性钠通道的开放概率和开放时间分别从0．021±0．007和(0．899±0．074)ms增加到0．205±0．023和(1．593±0．158)ms(P<0．叭,n=6),再加入还原剂DTT(1 mmol／L)使开放概率和开放时间分别回落到0．019±0．005和(0．868±0．190)ms(P<0．01 vs pH 6．5,n=6);加入蛋白激酶C(protein kinase C,PKC)抑制剂bisindolylmaleimide(BIM,5μmol/L)可使pH 6．5时增大的,ⅠNa.P明显减小,开放概率和开放时间分别从0．214±0．024和(1．634±0．137)ms回落到0．025±0．006和(0．914±0．070)ms(P<0．01 vs pH 6．5,n=6)。结果表明,细胞外pH值降低可诱发心室肌细胞ⅠNa.P增大,其机制可能与PKC的激活有关。     

兔室旁核对血量扩张引起促纳排泄与利尿的作用

在室旁核 (PVN)假损毁兔与PVN损毁兔血量扩张 (VE)引起尿流量增加 ,峰值分别为 0 5 9± 0 0 9与0 3 1± 0 0 3ml/min (P <0 0 1) ,排钠量增加峰值分别为 66 76± 6 74与 3 6 0 5± 3 4 4μmol/min (P <0 0 1) ,而在PVN假损毁兔与PVN完好兔对VE的反应无显著差别 (P >0 0 5 ) ,表明PVN损伤可明显减弱VE引起的促钠排泄与利尿效应。颈迷走神经切断并不能改变PVN损伤的上述作用。双侧肾神经切断兔损毁PVN对VE引起促钠排泄效应无显著影响 ,但显著减弱其利尿效应 (P <0 0 2 )。PVN损毁对VE时肾小球滤过率 (GFR)与肾血浆流量 (RPF)无显著影响。结果表明PVN参与VE通过迷走传入神经引起促钠排泄与利尿反应的调节 ,而肾交感传出神经参与其中促钠排泄的作用     

铁对血管收缩活动的影响及其机制

动脉粥样硬化的发生和铁引起的氧化应激密切相关。铁对血管的直接效应及其对血管收缩功能的影响尚不明确。本文采用血管环灌流装置 ,观察铁对离体SD大鼠去内皮胸主动脉环的直接效应 ,及对去内皮主动脉环KCl和苯肾上腺素 (PE)引发的收缩效应的影响。结果显示 :( 1) 10 0 μmol/L枸橼酸铁 (FAC)引起大鼠血管环发生相位性收缩 ,最大收缩幅度可达KCl诱发的最大收缩的 2 4 0 2± 2 3 7%。当 [Ca2 +]o 增加 1倍时 ,铁所致的血管环收缩幅度明显增加 (P <0 0 1)。阻断L 型钙通道后 ,铁所致的血管环收缩幅度明显降低 (P <0 0 1)。在无钙液中 ,用佛波酯收缩血管环 ,待收缩稳定后给予FAC ,此时收缩幅度增加 49 18± 3 75 %。 ( 2 )铁孵育 3 0min后 ,KCl引起血管环收缩的幅度显著降低 (P <0 0 1)。铁孵育可使PE引起的收缩量 -效曲线右移 (P <0 0 5 )。 ( 3 )二甲基亚砜、过氧化氢酶和谷胱甘肽可明显降低铁对PE血管收缩反应的抑制作用 (P <0 0 5 )。从这些结果可得到以下结论 :铁可引起胸主动脉发生相位性收缩 ,其机制可能与L 型钙通道短暂开放导致钙离子内流 ,及平滑肌对钙的敏感性增加有关 ;较长时间与铁孵育后 ,可对血管收缩功能产生损伤 ,氧自由基的生成增加和细胞内GSH的水平降低可能参与铁对收缩功能的     

心梗大鼠离体心脏的动作电位和不应期电生理研究

目的对比观察正常大鼠和心梗大鼠离体心脏动作电位和有效不应期的特点。方法用离体灌流吸附电极记录单向动作电位,常规电生理方法测量最大动作电位幅度(APA)、复极90%(MAP90)、复极50%(MAP50)、复极20%(MAP20)、有效不应期(ERP)。结果(1)和正常大鼠相比,心梗大鼠离体心脏左心房电生理参数MAP90(56.3±2.7vs.64.5±8.7,P<0.05)显著延长,ERP MAP90(0.89±0.2vs.0.78±0.3,P<0.05)减小,基础周期为250ms;右心室的电生理参数MAP90(67.6±14.1vs.134.1±26.7,P<0.001),ERP(55.0±3.53vs.69.0±8.9,P<0.05)明显延长,ERP MAP90(0.79±0.1vs.0.60±0.1,P<0.05)减小,基础周期为250ms;左心室的电生理参数MAP90(87.2±15.7vs.168.8±31.2,P<0.001)也呈显著延长,ERP(59.0±4.2vs.90.0±17.7,P<0.001),ERP MAP90(0.65±0.081vs.0.54±0.090,P<0.05)呈显著减小基础周期为250ms;(2)与正常大鼠相比,心梗大鼠的MAP90离散度[(LVMAP90-RVMAP90)(17.0±6.5vs.51.4±28.7,P<0.001)]、ERP离散度[(LVERP-RVERP)(4.0±2.2vs.20.0±7.9)P<0.001]显著增加,基础周期为250ms。结论心梗大鼠心脏不同部位的MAP的复极时间都显著性延长,MAP90和ERP离散度增加,这些电生理特点是促进折返形成、造成心律失常的主要原因。     

窦性节律下家兔心率与在位心室肌纤维有效不应期的关系

在自然呼吸和窦性节律下,用浮置式玻璃微电极引导在体单个左心室肌纤维动作电位,作为兴奋的指标,以其 0相触发产生期前的试验刺激,测定有效不应期(ERP)。38只家兔的测定结果表明,在R-R间期为205—330ms的范围内,随着心率加快(R-R间期缩短),ERP减小,而 ERP/RR 间期增大,说明 ERP 与心率直接有关。并且,在较快的心率时,ERP 相对延长。通过相关与回归分析,制出了能够删除心率影响的校正公式。静脉注射酒石酸锑钾(50mg/kg)发现,在窦性和起搏节律下,酒石酸锑钾均能轻度延长 ERP(P<0.001)。窦性节律下的校正后值与起搏节律的测定结果完全一致。证明校正后值能够用来比较处理前后不同心率条件下,各种药物、离子及其它因素对ERP 的影响。 本文的校正公式虽然只适用于同种动物和方法,但此校正公式的制作原理也可以广泛应用到其它多种动物。     

Effects of pituitary adenylate cyclase-activating polypeptide on canine atrial electrophysiology

We hypothesized that pituitary adenylate cyclase-activating polypeptide (PACAP) activates intracardiac postganglionic parasympathetic nerves and has a different effect than cervical vagal stimulation. We measured effective refractory period (ERP) and conduction velocity at four atrial sites [high right atrium (HRA), low right atrium (LRA), high left atrium (HLA), and low left atrium (LLA)] and minimum atrial fibrillation (AF) cycle length at 12 atrial sites during cervical vagal stimulation and after PACAP in 26 autonomically decentralized, open-chest, anesthetized dogs. PACAP shortened ERP to a similar extent at all four sites (HRA, 58 +/- 2.0 ms; LRA, 60 +/- 6.3 ms; HLA, 68 +/- 11.5 ms; and LLA, 60 +/- 8.3 ms). Low- and high-intensity vagal stimulation shortened ERP at the HRA, but not in the other atrial sites (low-intensity stimulation: HRA, 64 +/- 4.0 ms; LRA, 126 +/- 5.1 ms; HLA, 110 +/- 9.5 ms; and LLA, 102 +/- 11.5 ms; high-intensity stimulation: HRA, 58 +/- 4.2 ms; and HLA, 101 +/- 4.0 ms). Conduction velocity was not altered by any intervention. Minimum AF cycle length after PACAP was similar in both atria but was shorter in the right atrium than in the left atrium during vagal stimulation. After atropine administration, no interventions changed ERP. These results suggest that PACAP shortens atrial refractoriness uniformly in both atria through activation of intrinsic cardiac nerves, not all of which are activated by cervical vagal stimulation.     

Effects of sympathetic stimulation on use dependence of lidocaine, mexiletine, and quinidine in an intact canine model.

The use- or rate-dependent effects of a continuous infusion of lidocaine (n = 6, serum level 3.1 +/- 0.34 micrograms/mL), mexiletine (n = 8, serum level 7.08 +/- 0.90 micrograms/mL), and quinidine (n = 6, serum level 6.8 +/- 1.22 micrograms/mL) were studied in an open chest canine preparation. A use-dependent effect on conduction was assessed by measuring the change in the His to surface ventricular activation (HV) time at differing atrial paced rates during drug infusion. Global sympathetic activation was achieved by nondecentralized left stellate ganglion stimulation (4-10 Hz, 6-12 V, 2 ms) and use dependence at the same cycle lengths was compared. Repolarization times were measured from epicardial monophasic action potentials recorded from the anterior left ventricle throughout the study. There was no significant change in the HV time during control studies with or without left stellate stimulation. Use-dependent slowing of conduction was seen in all studies during drug infusion. This was evident at cycle lengths of 300-190 ms for quinidine and at cycle lengths less than 250 ms for lidocaine and mexiletine. Stellate stimulation attenuated use dependence in all studies. This effect was significant from cycle lengths of 300-190 ms for lidocaine and quinidine and at cycle lengths shorter than 230 ms for mexiletine (p less than 0.05). Stellate stimulation significantly reduced use-dependent prolongation of the HV interval by an average of 60%. During stellate stimulation there was a nonsignificant trend towards cycle length independent shortening of action potential duration both at baseline and in the presence of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is there a correlation between ventricular fibrillation cycle length and electrophysiological and anatomic properties of the canine left ventricle?

We hypothesized that myocardial infarction-related alterations in ventricular fibrillation (VF) cycle length (VFCL) would correlate with changes in local cardiac electrophysiological and anatomic properties. An electrophysiological study was performed in normal, subacute, and chronic infarction mongrel dogs. VF was induced by programmed electrical stimulation and mean and minimum early and late VFCL was determined and correlated with local electrophysiological and anatomic properties. Effective refractory period (ERP), activation recovery time (ART), ERP/ART ratio, threshold, and ERP and ART dispersion were determined at 112 sites on the anterior left ventricle. Wave front progression was analyzed over a 2-s period. The extent of local tissue necrosis and of myocardial fiber disarray was also evaluated. The early mean VFCL was significantly longer in the subacute infarction (149 +/- 35 ms) and chronic infarction dogs (129 +/- 18 ms) compared with control dogs (102 +/- 15 ms; P < 0.0001 for both comparisons) as was the early minimum VFCL with similar trends seen during late VF. Complete epicardial reentrant circuits were significantly more common in normal dogs (4.3 +/- 2.4, 22.4% of cycles) than in subacute (0.75 +/- 0.96, 5.3% of cycles, P < 0.05 vs. normal) and chronic infarction dogs (1.3 +/- 1.3, 7.5% of cycles, P < 0.05 vs. normal). There was a poor correlation between the mean and minimum early and late VFCL and local electrophysiological and anatomic properties (R(2) < 0.2 for all comparisons) with a much better correlation between average mean and minimum VFCL (over the entire plaque) and global ERP and ART dispersion during early and late VF. In conclusion, VFCL in normal and infarcted myocardium shows a poor correlation with local ventricular electrophysiological and anatomic properties measured in sinus rhythm. However, there was a much better correlation between the average VFCL with global dispersion of repolarization. The lack of correlation between local VFCL and refractoriness and the infrequent occurrence of epicardial reentry suggests that intramural reentry may be the primary mechanism of VF in this model.     

Effect of beta-adrenergic blockade on dynamic electrical restitution in vivo

The slope of the action potential duration (APD) restitution curve may be a significant determinant of the propensity to develop ventricular fibrillation, with steeper slopes associated with a more arrhythmogenic substrate. We hypothesized that one mechanism by which beta-blockers reduce sudden cardiac death is by flattening the APD restitution curve. Therefore, we investigated whether infusion of esmolol modulates the APD restitution curve in vivo. In 10 Yorkshire pigs, dynamic APD restitution curves were determined from measurements of APD at 90% repolarization with a monophasic action potential catheter positioned against the right ventricular septum during right ventricular apical pacing in the basal state and during infusion of esmolol. APD restitution curves were fitted to the three-parameter (a, b, c) exponential equation, APD = a.[1 - e((-b.DI))] + c, where DI is the diastolic interval. Esmolol decreased the maximal APD slope, 0.68 +/- 0.14 vs. 0.94 +/- 0.24 (baseline), P = 0.002, and flattened the APD restitution curve at shorter DIs, 75 and 100 ms (P < 0.05). To compare the slopes of the APD restitution curves at similar steady states, slopes were also computed at points of intersection between the restitution curve and the lines representing pacing at a fixed cycle length (CL) of 200, 225, 250, 275, and 300 ms using the relationship CL = APD + DI. Esmolol decreased APD restitution slopes at CLs 200-275 ms (P < 0.05). Esmolol flattens the cardiac APD restitution curve in vivo, particularly at shorter CLs and DIs. This may represent a novel mechanism by which beta-blockers prevent sudden cardiac death.     

Afterload and blood pressure amplitude in dilated cardiomyopathy]

The beat-to-beat variability of the diastolic blood pressure induces small variations in the afterload of the left ventricle. These variations influence myocardial contractility, and thus blood pressure amplitude. We assessed the interdependence of blood pressure and changes in the afterload. We continuously recorded blood pressure (duration 200 s, at rest) in 20 patients with dilated cardiomyopathy (ejection fraction 32 +/- 13%, left ventricular diameter 67 +/- 8 mm) and in 20 healthy volunteers. Interbeat intervals, diastolic pressures, systolic pressure amplitudes and mean slopes of systolic pressure amplitudes were measured. Correlation coefficients (r) were calculated to assess the interdependence of blood pressure amplitudes/mean systolic slopes and the preceding diastolic pressures/interbeat intervals, respectively. In healthy volunteers we found a strong interdependence between blood pressure amplitude and the preceding diastolic pressures (r = 0.62 +/- 0.21 and 0.47 +/- 0.22). Higher diastolic pressures were followed by higher blood pressure amplitudes, and by steeper slopes of the systolic peaks. In patients with dilated cardiomyopathy, such interdependence was significantly lower (r = 0.33 +/- 22 and r = 0.28 +/- 0.35), and in patients with severely reduced left ventricular function (ejection fraction < 32%) was only marginal (r = 0.23 +/- 0.27 and 0.21 +/- 0.44, respectively). The forces of the isovolumetric contraction necessary to initiate the ejection phase of the left ventricle depend on the afterload, i.e. on the diastolic pressure. The responses of amplitude and slope of the systolic blood pressure to small changes in the afterload make it possible to assess left ventricular contractility. The latter is impaired in dilated cardiomyopathy.     

Intrinsic changes on automatism, conduction, and refractoriness by exercise in isolated rabbit heart.

We have studied the intrinsic modifications on myocardial automatism, conduction, and refractoriness produced by chronic exercise. Experiments were performed on isolated rabbit hearts. Trained animals were submitted to exercise on a treadmill. The parameters investigated were 1) R-R interval, noncorrected and corrected sinus node recovery time (SNRT) as automatism index; 2) sinoatrial conduction time; 3) Wenckebach cycle length (WCL) and retrograde WCL, as atrioventricular (A-V) and ventriculoatrial conduction index; and 4) effective and functional refractory periods of left ventricle, A-V node, and ventriculoatrial retrograde conduction system. Measurements were also performed on coronary flow, weight of the hearts, and thiobarbituric acid reagent substances and glutathione in myocardium, quadriceps femoris muscle, liver, and kidney, to analyze whether these substances related to oxidative stress were modified by training. The following parameters were larger (P < 0.05) in trained vs. untrained animals: R-R interval (365 +/- 49 vs. 286 +/- 60 ms), WCL (177 +/- 20 vs. 146 +/- 32 ms), and functional refractory period of the left ventricle (172 +/- 27 vs. 141 +/- 5 ms). Corrected SNRT was not different between groups despite the larger noncorrected SNRT obtained in trained animals. Thus training depresses sinus chronotropism, A-V nodal conduction, and increases ventricular refractoriness by intrinsic mechanisms, which do not involve changes in myocardial mass and/or coronary flow.     

Transesophageal left ventricular posterior wall potential in heart failure patients with biventricular pacing.

INTRODUCTION: Biventricular (BV) pacing is an established therapy for heart failure (HF) patients with intraventricular conduction delay, but not all patients improved clinically. We investigated the interventricular delay (IVD) by means of the transesophageal left ventricular posterior wall potential (LVPWP). MATERIALS AND METHODS, AND RESULTS: A total of 18 HF patients (age 62+/-9 years; 15 males) with NYHA class 3.1+/-0.3, LV ejection fraction 22+/-7%, left bundle branch block and a QRS duration (QRSD) of 171+/-27 ms were analyzed using transesophageal LVPWP before implantation of a BV pacing device. The median follow up was 14+/-14 months. In 14 responders, IVD was 81+/-25 ms with a QRSD/IVD ratio of 2.2+/-0.3 with reclassification of NYHA class 3.1+/-0.3 to 2.0+/-0.5 (p<0.001) and an increase in LV ejection fraction from 22+/-7% to 36+/-11% (p=0.001) during long-term BV pacing. In four non-responders, transesophageal IVD was significantly smaller at 30+/-11 ms (p=0.001). CONCLUSION: Transesophageal IVD may be a useful method to detect responders to BV pacing. Transesophageal LVPWP may be a simple and useful technique to detect clinical responders to BV pacing in HF patients.     

Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF (n=18) and control (n=17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs)>1,000 ms but significantly shorter at BCLs<400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17-81%), and conduction velocity was significantly decreased in CHF (by 6-20%). In both groups, high-frequency stimulation (BCLs<150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs<150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.     

The effect of lidocaine compared with verapamil on the enhanced ventricular rhythm in the infarcted canine heart

Myocardial ischemia was produced in dogs by the occlusion of the left anterior descending (LAD) coronary artery for 24 or 48 h. After complete atrioventricular block was produced, enhanced ventricular rhythm was observed in all animals. The enhanced ventricular rhythm showed multiple QRS configurations and had spontaneous cycle lengths (SCL) of 397 +/- 18 ms (n = 20) after 24 h of LAD occlusion and 446 +/- 23 ms (n = 20) after 48 h of LAD occlusion. Overdrive pacing did not result in the termination of the enhanced ventricular rhythm in any experiment. Propranolol, as a cumulative dose of 1.5-2.0 mg/kg i.v., also did not abolish the enhanced ventricular rhythm. In 24-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 1 of 11 experiments. In the remaining 10 experiments, the ventricular SCL was increased from 401 +/- 22 to 491 +/- 26 ms after a cumulative dose of 8.8 +/- 0.7 mg/kg of lidocaine. In the presence of verapamil, given as a cumulative dose of 0.60 +/- 0.11 mg/kg, the ventricular SCL was increased from 401 +/- 33 to 482 +/- 64 ms (n = 9). In 48-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 5 of 11 experiments. Both lidocaine and verapamil increased the SCL of hearts in which the enhanced ventricular rhythm persisted. Analysis of variance showed that only the increase in SCL by lidocaine in 48-h infarcted hearts was statistically significant. The atrial and idioventricular rhythms in noninfarcted hearts responded differently to lidocaine and verapamil. The results suggest that some electrophysiological effects of antiarrhythmic drugs in the normal heart may not be applicable to those in the diseased situation.