Effects of 4-aminopyridine on contractile response and action potential of rabbit papillary muscle

The effects of 4-aminopyridine (4-AP) were studied on isolated papillary muscles from the heart of reserpinized rabbits (at 37°C). The preparations were paced to contract at 0.67 Hz under isometric conditions and the muscle length was adjusted to 95 % of the length for optimum force production. Simultaneous recordings of isometric force and membrane potentials were performed. 4-AP (50 μM) increased peak force by approximately 20% of the control and prolonged the action potential by 20%. Higher concentrations of 4-AP (800 μ.M) resulted in further increments of force and action potential duration (60 and 70% of controls, respectively). Prolongation of the action potential and potentiation of the isometric force was still present one hour after withdrawal of the drug from the perfusate. The results are consistent with the view that 4-AP prolongs the action potential by inhibiting the late repolarizing potassium current. It is suggested that the calcium uptake by the ventricular cell during the prolonged action potential is increased and that this leads to the positive inotropic effect.     

The preferential inhibition of α1- over β-adrenoceptor-mediated positive inotropic effect by organic calcium antagonists in the rabbit papillary muscle

Summary Experiments were carried out to elucidate the mechanism that the positive inotropic effect mediated by ₁-adrenoceptors is more susceptible to organic calcium antagonists than the -adrenoceptor-mediated effect. Verapamil and diltiazem displaced the specific binding of [³H]prazosin to the membrane fraction derived from the rabbit ventricular myocardium, verapamil being about 70 times more potent than diltiazem. Nifedipine did not displace the binding. While these compounds suppressed the positive inotropic effect mediated via _l-adrenoceptors in ₁- concentration-dependent manner, there was no correlation between the potency of the compounds to displace the [³H]prazosin binding and to inhibit the -mediated positive inotropic effect. The relative potency of three calcium antagonists to decrease the basal force of contraction and the al-mediated effect (of the same extent as compared to basal force of contraction) was consistent to each other. The positive inotropic effect mediated by -adrenoceptors was inhibited much less, and was enhanced by low concentrations of organic calcium antagonists. The differential action of calcium antagonists on the - and -mediated positive inotropic effect was mimicked by lowering the extracellular calcium concentration to 1/2, 1/4 and 1/8 of that in normal Krebs-Henseleit solution (2.5 mmol/l). These results indicate that the ₁-adrenoceptor blocking activity does not play an essential role for the preferential inhibition of -mediated positive inotropic effect by organic calcium antagonists. Difference in the subcellular mechanism involved in mobilization of intracellular Ca²⁺ subsequent to ₁-and -adrenoceptor activation may be responsible for the differential inhibitory action of calcium antagonists in the rabbit heart. Send offprint requests to M. Endoh at the above address     

Myocardial protection of immature rabbits with an ATP- sensitive K+ channel opener pinacidil

Objective To investigate the effectiveness of pinacidil, an opener of ATP- sensitive K(+) channels, in protecting the myocardium of immature rabbit hearts from ischemic r eperfusion injury. Methods Rabbit hearts underwent 30 min of global normothermic ischemia followed by 30 mi n of reperfusion on the modified Langendorff apparatus. Fifty- two isolated hea rts of 3-4 week- old immature rabbits were divided into 4 groups randomly. Duri ng ischemia, 3 different cardioplegic solutions were administered intermittently by infusion every 15 min (20-25 ml each time in all groups). Group 1: con trol group (n=13); group 2: Krebs- Henseleit (K- H) solution with potassium (16 mmo l/L) (n=13); group 3: K- H solution with potassium (16 mmol/L) and pinacidil (5 0 μmol/L) (n=13); group 4: K- H solution with potassium (16 mmol/L), pinacidi l (50 μmol/L) and glibenclamide (10 μmol/L) (n=13). The pre- ischemic and p ost- ischemic myocardial functions were assessed by the percentage recovery of t he left ventricular developed pressure (LVDP); the left ventricular end- diastol ic pressure (LVEDP); both the positive peak and negative peaks of the first deri vative of the left ventricular pressures (±dp/dt(max)); coronary flow; the level of creatine kinase (CK), lactic dehydrogenase (LDH) and aspartate transcar bamoylase (AST) in coronary sinus venous effluent; and by myocardial ultrastruct ural changes. Results Before myocardial ischemia, there were no significant differences among the four groups in any of the parameters mentioned above. Post- ischemic recovery of LV DP, LVEDP, ±dp/dt(max), coronary flow, the level of CK, LDH and AST, and my ocardial ultrastructural changes were better in group 3 than those in the three other groups.Conclusions As a new and effective composition, pinacidil can significantly improve myocardi al protection from cardioplegia for immature rabbit hearts.     

声学密度定量分析技术评价尿毒症性心肌损害的临床研究

目的：探讨声学密度定量分析技术在尿毒症性心肌损害诊断方面的定量诊断价值。方法：对21例尿毒症及21例正常人心肌各节段声学密度及心肌声学密度校正值（IB％）进行测定及比较。结果：尿毒症患者心肌各节段平均声学密度（AⅡ）均明显高于正常人（P＜0．01）,2组的峰值－峰值密度（PPI）及标准密度差（SDI）差异不显著（P＞0．05）,2组左心腔内PPI、AⅡ、SDI差异均不显著（P＞0．05）,尿毒症组心肌各节段IB％明显高于正常人（P＜0．01）。结论：声学密度定量分析技术能定量、客观地反映尿毒症患者的心肌损害情况,对临床检测尿毒症 损害具有实用价值。     

缓激肽对缺血-再灌注兔心肌能量代谢的延迟性作用

目的　通过在体兔心肌缺血再灌注模型探讨缓激肽(BK)对缺血再灌注心肌能量代谢的延迟性影响 .方法　 36只健康新西兰兔 ,随机分为 3组 . 组 (对照组 ) :建立动物模型后关胸 ,2 4h后心肌缺血 40 m in,再灌注 6 0 m in. 组 (BK组 ) :建立动物模型后给予 BK左室内灌注 5 0 μg· (kg·min) - 1 ,共 10 m in,其余同 组 . 组 (HOE140组 )第 1日建立模型后输注 BK时给予 BK B2 受体拮抗剂 HOE140 iv10μg· kg- 1 ,其余同 组 .分别测定各组缺血 2 0 min,40 m in及再灌注后心肌 ATP、磷酸肌酸、糖原及乳酸含量 .结果　 BK组在缺血 2 0 min时 ATP、磷酸肌酸、糖原含量明显高于对照组 ,乳酸含量低于对照组 ;缺血 40 m in BK组 ATP、磷酸肌酸、糖原及乳酸与对照组相比无明显差异 ;再灌注后 ATP、磷酸肌酸、糖原含量再次明显高于对照组 ,乳酸含量与对照组相比则明显降低 .而 HOE140组各项指标同对照组相比无明显差异 .结论　 BK能够延迟性改善兔心肌缺血再灌注的能量代谢     

活血通脉片对大鼠异丙肾上腺素心肌损伤的保护作用

目的：研究中药复方制剂活血通脉片（Huoxue TOngmai tablet,HXTMT)对异丙肾上腺素（isoproterenol,ISO)心肌损伤大鼠的保护作用,方法：用HXTMT给SD大鼠连续灌胃14d,第12日起动物sc ISO(48umol.kg^-1.d^-1),每日一次,连续3d,复制异丙肾上腺素性心肌损伤大鼠模型。结果：中药复方制剂HXTMT能明显减轻心肌损伤程度,血清CK活性,心肌MDA含量,心肌含水量分别减少14％,25％,2％,与模型组比较有显性差异（P＜0．05）,结论：HXTMT能稳定细胞膜,减轻心肌水肿程度,阻止脂质过氧化物的形成,提示HXTMT对心肌缺血性损伤有细胞保护作用。     

大鼠严重烧伤早期心肌线粒体Ca2+转运变化及其机制研究

目的 探讨严重烧伤早期心肌线粒体Ca^2 转运变化及其发生机制。方法 复制30%Ⅲ度烫伤大鼠模型,测定伤后1、3、6、12、24h大鼠心肌线粒体Ca^2 转运速率,同时检测影响Ca^2 转运的相关指标--心肌细胞胞浆Ca^2 浓度（[Ca^2 ]c）、线粒体膜电位及ATP含量。结果 伤后1h心肌线粒体Ca^2 摄取速率明显升高,而Ca^2 释放速率无明显改变,但3、6、12、24h心肌线粒体Ca^2 摄取与释放速率、线粒体膜电位、ATP含量均显著降低,且烧伤后线粒体Ca^2 摄取速率与膜电位呈明显正相关,Ca^2 释放速率与线粒体ATP含量呈显著正相关。而伤后3、6、12、24h[Ca^2 ]c均明显高于正常对照组。结论 ①烧伤初始心肌线粒体Ca^2 摄取加强,伤后续阶段线粒体Ca^2 转运紊乱;②线粒体膜电位下降、ATP含量降低是烧伤后续阶段心肌线粒体Ca^2 转运紊乱的主要原因,伤后[Ca^2 ]c升高或有升高趋势也参与严重烧伤早期心肌线粒体Ca^2 转运变化的发生。     

低心室容量负荷未能影响兔离体心肌的氧耗反应时间

为了解心肌容量负荷是否影响心肌的氧化磷酸化过程,采用兔离体灌流心肌线粒体氧耗反应时间测定方法,对一下正常心室容量负荷和低心室容量负荷时的心肌线粒体氧耗反应时间进行比较,结果提示心肌作功负荷变化未能影响心肌线粒体的能量代谢动态调节过程。