Dissimilar Action of Two Cyclic Adenosine-Monophosphate Analogues on the Sodium Current in Intact Rat Papillary Muscle

In intact papillary muscles from rat we have found with the loose-patch-clamp technique an increase of the fast cardiac sodium current (I_Na⁺) by isoproterenol (ISO). In this study we have tested two membrane permeable analogues of the intracellular second messenger cyclic adenosine-monophosphate (cAMP) to investigate the intracellular pathway: 8-Br-cAMP (50 μM) and the newer developed S_p5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole-3′, 5′-cyclic-monophosphor-othioate (5,6-DCl-cBiMPS, 20 μM). The availability of I_Na⁺ was determined with test pulses to ± 0 mV every 3.5 seconds after 2.5-second conditioning between -130 mV and-50 mV and a holding potential at the resting potential of the cell under examination, and after wash-in of either compound. The peak currents were fit to a Boltzmann equation, and expressed by the maximal attainable current INa⁺_Na,max the mid-point potential V½, and a steepness parameter a. Values are given by mean ± SEM. 8-Br-cAMP showed a significant shift of the availability curve in the hyperpolarized direction (V½= -82 ± 2 mV vs - 66 ± 2 mV, n = 5, P < 0.05) with only minor changes of I⁺_No,max and a. In contrast, 5,6-DCI-cBiMPS had no significant effect on V½ but increased I⁺_Na,max by 8%± 2% versus control (n = 5. P < 0.05). In an intact muscle preparation we have found that 5,6-DCI-cBiMPS has a similar effect as that observed with the β-adrenergic agonist ISO (100 nM), whereas 8-Br-cAMP exhibited a dissimilar action. This indicates, that ihe effects of ISO are transmitted by the cAMP system. On the other hand, 8-Br-cAMP, which is not as permeable and specific an activator of the cAMP dependent proteinkinase, may have other effects on the sodium channel, perhaps mediated through purinergic receptors.     

米力农与硝普钠合用治疗难治性心力衰竭的临床价值

目的:观察米力农与硝普钠合用治疗难治性心力衰竭患者的疗效。方法:选择90例难治性心力衰竭患者,随机分为A、B、C三组各30例,分别用米力农(对照组)、多巴酚丁胺(对照组)和米力农+硝普钠组(实验组)治疗,观察患者治疗前后心功能级别和心脏超声心功能指标(EF、CO、SV、CI和VA/VE)的变化情况。结果:A、B、C组总有效率分别为57%、47%和87%,差异有显著性(P<0.05)。结论:米力农适用治疗难治性心衰,尤其是不能耐受洋地黄药物治疗者,与硝普钠合用,临床疗效显著增加。     

Influence of Different Atrioventricular and Interventricular Delays on Cardiac Output During Cardiac Resynchronization Therapy

Restoration of the atrioventricular (AVD) and interventricular (VVD) delays increases the hemodynamic benefit conferred by biventricular (BiV) stimulation. This study compared the effects of different AVD and VVD on cardiac output (CO) during three stimulation modes: BiV-LV = left ventricle (LV) preceding right ventricle (RV) by 4 ms; BiV-RV = RV preceding LV by 4 ms; LVP = single-site LV pacing. We studied 19 patients with chronic heart failure due to ischemic or idiopathic dilated cardiomyopathy, QRS ≥ 150 ms, mean LV end-diastolic diameter = 78 ± 7 mm, and mean LV ejection fraction = 21 ± 3%. CO was estimated by Doppler echocardiographic velocity time integral formula with sample volume placed in the LV outflow tract. Sets of sensed-AVDs (S-AVD) 90–160 ms, paced-AVDs (P-AVD) 120–160 ms, and VVDs 4–20 ms were used. BiV-RV resulted in lower CO than BiV-LV. S-AVD 120 ms and P-AVD 140 ms caused the most significant increase in CO for all three pacing modes. LVP produced a similar increase in CO as BiV stimulation; however, AV sequential pacing was associated with a nonsignificantly higher CO during LVP than with BiV stimulation. CO during BiV stimulation was the highest when LV preceded RV, and VVD ranged between 4 and 12 ms. The most negative effect on CO was observed when RV preceded LV by 4 ms. Hemodynamic improvement during BiV stimulation was dependent both on optimized AVD and VVD. LV preceding RV by 4–12 ms was the most optimal. Advancement of the RV was not beneficial in the majority of patients.     

氨基末端脑利钠肽前体对无症状性心功能不全诊断价值的研究

【目的】探讨无症状性心功能不全患者氨基末端脑利钠肽前体（NT-proBNP）血浆浓度的变化规律,为早期诊断心功能不全提供依据。【方法】选择在本院住院无心功能不全症状的高危者120例作为研究对象,检测其NT—proBNP浓度,依据NT-proBNP水平将120例受试者分为NT—proBNP升高组（试验组）和NT-proBNP正常组（对照组）,并进行心脏彩色多普勒超声检查,测定其左室射血分数（LVEF）、舒张早期心室最大充盈速度／舒张晚期心室最大充盈速度（E／A）、左室舒张末期内径（LVEDD）、室间隔厚度（IVST）、左室后壁厚度（LVPWT）、左室短轴缩短分数（FS）,对两组样本各项心功能指标进行比较分析,并对NT—proB—NP水平和各项心功能指标进行相关性分析。【结果】试验组左室收缩功能和舒张功能各指标均较对照组差（P〈0．05）,提示存在心功能不全。【结论】无症状人群血浆NT—proBNP浓度升高提示心功能不全,NT—proBNP可作为心功能不全的早期诊断依据之一,其升高程度与心功能受损程度呈正相关。     

蛇床子素对大鼠心室肌细胞钠通道的影响

目的探讨蛇床子素对大鼠心室肌细胞钠离子通道电流(INa)的影响。方法采用Langendorff装置,恒压恒温灌流及酶解消化等方法对大鼠心肌细胞进行分离和处理。应用膜片钳技术,观察给予不同浓度蛇床子素(Ost)后钠离子通道电流特征的变化。结果 Ost(100μmol/L)能明显抑制钠电流,其作用呈浓度依赖性(500μmol/L几乎完全阻断)和时间依赖性(10 min左右抑制力达到最强)。100μmol/L和300μmol/L Ost使钠电流I-V曲线明显上移,峰值钠电流(-29.8±4.21)p A/p F分别降为(-20.1±3.7)p A/p F和(-17.7±5.7)p A/p F(P0.05),但激活电位和峰电位没有改变。对于钠通道失活曲线,不同浓度的Ost能使其向超级化方向移动,V1/2(空白,100μmol/L,300μmol/L)分别为(-81.10±0.35)、(-91.62±1.06)、(-100.60±0.21)m V(P0.01)。Ost还能显著延长钠通道失活后恢复时间,τ(空白,100μmol/L,300μmol/L)分别为(15.09±0.78)、(23.41±1.23)、(31.62±0.97)ms(P0.01)。结论 Ost对大鼠心室肌钠通道电流有明显的抑制作用。     

氨茶碱对大鼠膈肌细胞L型钙通道的影响

目的:研究氨茶碱对大鼠膈肌细胞L型钙通道的电生理作用。方法:采用全细胞膜片钳（whole cell patchclamp）技术,当维持电位为-80mv,刺激频率为0.5Hz,钳制时间为300ms,步进电压为10mv,去极到60mv,观察氨茶碱对膈肌细胞L型钙通道（L-ICa）的影响。结果:氨茶碱用药后大鼠膈肌细胞平均内向峰值L型钙电流为（-6.5±0.5）pA/pF;正常未用药组为（-5.6±0.5）pA/pF,其增加的幅度为14.6±2.5％,两组比较差异有显著性（P<0.01）。结论:氨茶碱可激活膈肌细胞膜的钙通道,增加Ca2+内流,而使膈肌细胞的收缩力增强,为临床治疗膈肌疲劳提供理论依据。     

促红细胞生成素对慢性心力衰竭合并贫血患者的心功能的影响

目的：探讨促红细胞生成素（EPO）治疗慢性充血性心力衰竭（CHF）合并贫血患者的疗效。方法：2007年1月—2009年12月慢性充血性心力衰竭合并贫血的住院治疗患者96例,随机分为常规抗心衰治疗组（48例）和加用促红细胞生成素（EPO）及口服铁剂治疗组（48例）,共治疗2个月,随访观察6个月,比较2组治疗前后血浆脑钠肽（BNP）水平、心功能分级、左室舒张末期内径（LVDd）、左室射血分数（LVEF）、血红蛋白（Hb）水平、心衰再入院率、心源性病死率等指标的变化。结果：EPO联合铁剂治疗组患者BNP水平、心功能分级、LVEF值、Hb水平均较治疗前显著改善（均P〈0.01）,并且显著优于常规抗心衰治疗组（均P〈0.01）,心衰再入院率也显著下降（P〈0.05）,但2组病死率无显著差异（P〉0.05）。结论：EPO联合铁剂治疗慢性充血性心力衰竭合并贫血可显著改善患者心功能,降低心衰患者再住院率。     

Effects of Cardiac Resynchronization Therapy on Diastolic Function: Evaluation by Radionuclide Angiography

While the beneficial effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) systolic function have been demonstrated, no information is available regarding its effects on LV diastolic function during exercise. Using radionuclide angiography, we prospectively evaluated the effects of CRT on diastolic function at rest and during exercise in 15 patients consecutively referred for CRT. All patients underwent equilibrium Tc⁹⁹ radionuclide angiography with bicycle exercise performed (1) at baseline; (2) immediately after CRT implantation, in spontaneous rhythm and during CRT; and (3) after 3 months of biventricular stimulation. Diastolic function was assessed by measurements of peak filling rate (PFR). At baseline, activation of biventricular stimulation influenced PFR neither at rest (1.06 ± 0.34 vs 1.07 ± 0.50 mL/s during spontaneous rhythm, P = 0.9) nor during exercise (1.45 ± 0.62 vs 1.33 ± 0.48 mL/s, P = 0.3). At 3 months, improvements were observed in New York Heart Association functional class and systolic function. By contrast, no improvement in diastolic function was observed either at rest (PFR = 1.11 ± 0.45 vs 1.07 ± 0.50 mL/s in spontaneous rhythm at baseline, P = 0.6) or during exercise (1.23 ± 0.50 vs 1.33 ± 0.48 mL/s, P = 0.2). These observations indicate that the intermediate benefits conferred by CRT on LV systolic function at rest and during exercise were not accompanied by similar improvements in diastolic function .     

Influence of Internal Current and Pacing Current on Pacemaker Longevity

The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8. 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 ±0.1 μA; Pasys: 16.1 ± 0.1 μA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V puise amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0–2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. Conclusion: Extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.     

冻干重组人脑利钠肽治疗急性心力衰竭32例临床分析

目的:观察冻干重组人脑利尿钠肽(rhBNP)治疗急性心力衰竭的疗效.方法:将2009年8月至2011年5月收治的急性心力衰竭患者63例随机分为观察组(n=32)和对照组(n=31),分别在常规治疗的基础上给予rhBNP和硝普钠治疗,比较两组临床疗效和血浆脑利尿钠肽(BNP)浓度.结果:观察组治疗后的各项指标均较对照组明显好转(P均<0.05).结论:冻干重组人脑利尿肽治疗急性心力衰竭疗效明确,不良反应发生率低.     

曲美他嗪对缺血性心脏病心力衰竭患者心室重塑和心功能的影响

【目的】探讨曲美他嗪 (trimetazidine,TMZ)对缺血性心脏病心力衰竭患者心室重塑和心功能的影响。【方法】缺血性心脏病心力衰竭患者 78例 ,左室射血分数≤ 4 0 % ,心功能 (NYHA)Ⅱ～Ⅳ级 ,常规治疗基础上随机分为TMZ组 (n =4 0 ) )和对照组 (n =38)。治疗 6个月 ,观察曲美他嗪对心室重塑和心功能的影响。【结果】经过 6个月治疗 ,TMZ治疗组症状和心功能改善 ,与对照组比较左室收缩末容积下降 [(15 9.2±4 6 .7)mlvs (179.8± 4 8.5 )ml,P <0 .0 5 ],左室收缩末内径减小 [(32 .7± 4 .1)mmvs (39.5± 3.9)mm ,P <0 .0 5 ],左室射血分数显著提高 [(48.6± 9.5 ) %vs (35 .2± 8.7) % ,P <0 .0 1];与基线比较左室舒张末容积下降 (P <0 .0 5 ) ,左室舒张末内径减小 (P <0 .0 5 ) ,但两组间无统计学差异。【结论】在心力衰竭标准治疗基础上 ,应用TMZ能显著改善缺血性心脏病心力衰竭患者心室重塑和心功能。     

抗Nav1.5抗体对豚鼠心室肌细胞钠电流的影响

目的了解钠通道亚型特异性抗体——抗Nav1．5抗体对豚鼠心室肌细胞钠电流的影响。方法用急性酶解法获得成年豚鼠单个心室肌细胞,并行随机分组,各组分别给予不同稀释浓度的抗体（15μg／ml）（室温下）处理10min：（1）1：100抗体稀释组给予0．15μg／ml抗体处理;（2）1：50抗体稀释组给予0．30μg／ml抗体处理;（3）1：25抗体稀释组给予0．60μg／ml抗体处理;（4）对照组（未给予抗体处理）。而后分别进行全细胞膜片钳实验测定钠电流并计算电流密度。数据采用one-way方差分析及SNK检验、Dunnett检验。结果与对照组相比,三个抗体处理组（抗体浓度分别为0．15、0．30和0．60μg／ml）的,INa峰值从对照组的（0．026296±0．004436）nA／pF分别降至（0．01841±0．007161）nA／pF（P〈0．01,n=10）、（0．013484±0．002933）nA／pF（P〈0．01,n=9）和（0．012738±0．004554）nA／pF（P〈0．01,n=8）,并使INa的I-V曲线上移,激活电位、峰电位和翻转电位无明显改变。三个不同浓度抗体处理组之间的电流密度虽有差异,但差异并无统计学意义（P〉0．05）。结论抗Nav1．5抗体可抑制心室肌细胞钠电流,但无浓度依赖性。     

曲美他嗪对冠心病慢性心力衰竭患者心功能及心率震荡的影响

目的观察曲美他嗪对冠心病慢性心力衰竭患者心功能及窦性心率震荡(HRT)的影响。方法2009 年10 月~2012 年6月经冠脉造影和/或CT血管造影(CTA)证实的73 例冠心病慢性心力衰竭患者,随机分成对照组(n=35)和曲美他嗪组(n=38)。对照组采用常规强心、利尿、扩血管等抗心力衰竭治疗;曲美他嗪组在此基础上给予口服曲美他嗪片。两组分别于服药前和服药3 个月后检查心脏彩色多普勒超声心动图、24 h 动态心电图,测算左心室射血分数(LVEF)、左室舒张末期内径(LVd)以及反映HRT的两个量化指标震荡初始(TO)和震荡斜率(TS)。结果经3 个月治疗,两组LVEF提高,LVd缩小(P<0.01)。曲美他嗪组LVEF改善显著优于对照组(P<0.001)。曲美他嗪组TO和TS均改善(P<0.05),对照组仅TO改善(P<0.05)。曲美他嗪组TO和TS改善均优于对照组(P<0.05)。结论曲美他嗪有助于改善冠心病慢性心力衰竭患者的心功能,改善HRT现象。     

The antagonist properties of S 11978 on 5HT3 receptors in N1E-115 neuroblastoma cells

Summary— The effects of the novel antagonist S 11978 (Endo-7-[(8-methyl-8-azabicyclo[3,2,1]-3-octyl)oxycarbonyl] benzo[b] thiophene) on 5HT₃ receptors were examined in N1E-115 mouse neuroblastoma x rat glioma hybrid cells, with radioligand binding and whole cell patch clamp techniques. The 5HT₃ receptor ligand [³H] quipazine was displaced by ICS 205–930, GR 38032F and S 11978 with K_I values of 2.25 nM, 36.5 nM and 1.75 nM respectively. Electrophysiological studies showed that S 11978 is a potent 5HT₃ antagonist: IC₅₀ values for inhibition of 5HT-induced inward current by ICS 205–930, GR 38032F and S 11978 were 0.22 nM, 0.63 nM and 0.43 nM respectively at a holding potential of-65 mV. It is concluded that S 11978 is a potent, high affinity 5HT₃ receptor antagonist.     

预见性护理干预对慢性心力衰竭患者心功能的影响

目的探讨预见性护理干预对慢性心力衰竭患者心功能的影响。方法 将286例心功能为Ⅱ、Ⅲ级的患者按随机数字表法分为实验组和对照组,两组各143例。实验组患者给予预见性护理,即进行预见性评估、与患者及家属共同制定预见性护理计划、实施预见性护理方案等。对照组患者给予常规护理。观察两组患者血浆B型钠尿肽（B-type natriuretic pep-tide,BNP）水平、射血分数（ejection fraction,EF）、心输出量（cardiac output,CO）、心率、血压的变化。结果经过治疗和护理,两组患者的BNP均明显降低（均P〈0.01）,且实验组与对照组比较差异有统计学意义（P〈0.01）。两组患者干预后心率及血压均明显下降,与干预前比较差异有统计学意义（P〈0.05）;干预后实验组患者的心率及血压与对照组比较差异有统计学意义（P〈0.05）。实验组患者干预后CO、EF与对照组相比,差异有统计学意义（P〈0.01）。结论预见性护理干预使血中BNP浓度降低,改善了患者的心功能。