葛根素对豚鼠心肌细胞动作电位及有效不应期的影响

目的　观察葛根素对豚鼠乳头肌动作电位及有效不应期的影响 ,以探讨其抗心律失常的作用机制。方法　采用标准玻璃微电极细胞内记录技术。结果　①葛根素 0 0 0 5 ,0 0 1,0 0 15mmol·L-1能使豚鼠心室肌细胞动作电位复极5 0 %时程 (APD50 )和复极 90 %时程 (APD90 )明显延长 ,APD50分别由 ( 176 4 3± 5 1 3 7)ms延长至 ( 192 86± 60 82 )ms(n=7,P <0 0 5 ) ,( 2 0 0 71± 63 0 8)ms和 ( 2 0 7 71± 65 4 5 )ms(n =7,P <0 0 1) ;APD90 分别由 ( 2 0 0 71± 5 9 75 )ms延长至 ( 2 2 1 4 3± 70 4 6)ms(n =7,P <0 0 5 ) ,( 2 3 5 0 0±5 8 88)ms和 ( 2 4 0 0 0± 5 8 4 5 )ms(n =7,P <0 0 1) ,并且这种延长呈现量效关系。②采用 0 2 ,0 5 ,1,2 ,4Hz频率的方波刺激 ,发现在 0 0 1mmol·L-1时葛根素延长心肌细胞APD50 有明显的非逆向频率依赖性。③使用双脉冲刺激发现在 0 0 1mmol·L-1时葛根素能明显延长心肌细胞的有效不应期 ,由 ( 98 0 0± 16 4 3 )ms延长至 ( 168 0 0± 13 0 4 )ms(n =5 ,P <0 0 1)。结论　葛根素能延长心肌细胞APD50 和APD90 以及心肌细胞有效不应期 ,其抗心律失常的机制源于此作用。     

双黄连粉针剂对豚鼠心肌电生理的影响

目的探讨双黄连粉针剂对豚鼠心脏电生理的影响,以及其心脏安全性及作用机制。方法①在体实验:双黄连粉针剂325.5,1627.5和3255.0mg·kg-1分别在两组动物进行,每组15只。一组动物按照生理盐水→双黄连粉针剂325.5→1627.5mg·kg-1,另一组按照生理盐水→双黄连粉针剂3255.0mg·kg-1的顺序经颈外静脉缓慢推注,持续5min。于给生理盐水及静脉推注各剂量药物后5min记录心电图,分析P-R间期和校正QT间期(QTc)。②离体实验:按照灌流液(空白对照)→双黄连粉针剂0.3→1.5→3→9g·L-1→洗脱的顺序灌流,持续5min。于灌流5min末记录豚鼠离体心脏心电图,分析7只豚鼠的P-R间期和QTc间期;记录左心室乳头肌动作电位,分析5只豚鼠的动作电位复极50%水平时程(APD50)和90%水平时程(APD90)。结果①在体豚鼠心电图表明,双黄连粉针剂325.5和1627.5mg·kg-1显著延长P-R间期,从生理盐水处理时的(59±5)ms分别延长到(74±10)ms和(88±20)ms(P<0.05),各浓度组的QTc间期无明显变化;双黄连粉针剂3255.0mg·kg-1处理P-R间期则从生理盐水处理时的(58±5)ms延长到(133±29)ms(P<0.05),QTc从(247±16)ms延长到(301±65)ms(P<0.05),并显示明显的室内传导阻滞。②离体豚鼠心电图表明,双黄连粉针剂3和9g·L-1使空白对照组P-R间期从(84±17)ms延长到(113±39)ms和(130±23)ms(P<0.05),伴有明显的室内传导阻滞,而各浓度组的QTc间期无明显变化。双黄连粉针剂各浓度组对正常豚鼠左心室乳头肌动作电位APD50与APD90无明显作用。结论注射用双黄连粉针剂能引起豚鼠房室和室内传导阻滞,其作用机制可能是抑制心肌细胞钠通道。     

莲心总碱及其甲基化物对牵张性心律失常的拮抗效应(英文)

目的　澄清莲心总碱 (TAL)与氨基糖苷类抗生素的共同化学结构带正电的氨基是否使之具有抗牵张性心律失常的共同效应。方法　通过膨胀心室腔内的球囊、夹闭升主动脉和牵拉乳头肌建立心律失常、动作电位时程的缩短和触发活动的模型。采用离体心电图、细胞内微电极和在体单相动作电位的标准技术进行记录。结果　①TAL和甲基莲心总碱 (TMAL) (2 .5 ,5和 10 μmol·L- 1)能剂量依赖性的缩短大鼠离体心脏牵张性心律失常的持续时间 ,从对照组的 (2 .16± 0 .38)s减少到 (1.5 3± 0 .14 ) ,(0 .93± 0 .2 1) ,(0 .5 2± 0 .35 )s (TAL )和(1.5 9± 0 .16 ) ,(0 .94± 0 .2 1) ,(0 .79± 0 .15 )s(TMAL)。②在麻醉豚鼠 ,TAL 2 .3mg·kg- 1iv和TMAL 2 .6mg·kg- 1iv能显著抑制夹闭主动脉引起的单相动作电位 5 0 %和 90 %复极时程的缩短及触发活动的发生率 ,分别从 (2 8.9± 8.1) %减少到(5 .4± 1.2 ) %和 (10 .8± 2 .3) %。③TAL和TMAL也能显著抑制牵拉豚鼠乳头肌所致的动作电位 5 0 %和 90 %复极时程的缩短。结论　TAL和TMAL能抑制牵张性心律失常和牵张引起的动作电位的改变 ,这种作用可能是通过阻断牵张活化的离子通道实现的。     

一种筛选抗心律失常药物新模型的建立

目的　建立一种细胞水平的心律失常模型 ,以用于抗心律失常药物的筛选和评价。方法　酶解法分离单个大鼠心室肌细胞 ,在细胞水平给予传统诱发心律失常药物乌头碱 ,应用膜片钳技术观察记录应用乌头碱后心肌动作电位时程 (APD)、钠电流 (INa)、L 型钙电流 (ICa L)、内向整流钾电流(IK1)及瞬时外向钾电流 (Ito)的变化。结果　应用乌头碱 1μmol·L-1使大鼠单个心室肌细胞 90 %复极化动作电位时程(APD90 )从给药前的 ( 15 0 2 3± 7 0 2 )ms延长至 ( 2 3 6 0 3±2 3 2 2 )ms(n =8,P <0 0 1)。应用奎尼丁 10 μmol·L-1后动作电位时程延长与乌头碱组比较 ,APD90 进一步延长 (n =6,P <0 0 5 ) ,但应用维拉帕米 10 μmol·L-1后被乌头碱延长的APD恢复近于正常 ,在乌头碱的作用下 ,除极电压为 0mV时ICa L从 ( 72 7 9± 178 0 ) pA增加至 ( 10 82 1± 2 2 2 2 ) pA(n =6,P <0 0 1) ;钠电流 (INa)在 - 5 0mV刺激电压下从( 2 5 4± 5 5 3 ) pA增加至 ( 45 3 0 2± 475 1) pA(n =4,P <0 0 5 ) ;IK1在 - 12 0mV的刺激电压下 ,Ik1的内向成分从( 2 0 0 7 1± 3 5 9 3 ) pA增加至 ( 2 3 17 7± 40 1 8)pA(n =10 ,P <0 0 1) ;奎尼丁、维拉帕米对乌头碱诱发的钠电流和钙电流增加有抑制的作用。结论　乌头碱使?     

心律泰对离体豚鼠乳头肌动作电位的影响

目的:研究心律泰对离体豚鼠乳头肌动作电位的影响。方法:采用标准微电极细胞内记录技术。结果:心律泰呈浓度依赖性地降低离体豚鼠乳头肌动作电位(AP)的Vmax、APA,缩短APD20、APD50、APD90。中浓度时(4 mg生药／ml),使Vmax, APA,APD20,APD50,APD90由给药前的122．6±25．4 v／s,98．0±10．8 mv,114．4±16．7 ms,174．7±25．0 ms,250．4±39．2 ms分别降为115．9±25．4 v／s,89．7±11．2 mv,107．7±14．8 ms,164．9±26．7 ms,234．4±39．4 ms,心律泰对RP无影响。结论:心律泰抗心律失常的可能机制与抑制Na ,Ca2 内流、促进K 外流有关。     

苄基四氢巴马汀对心室肌动作电位和延迟整流钾电流的频率依赖性作用

目的　研究BTHP对豚鼠乳头状肌动作电位及单个心室肌细胞延迟整流钾电流影响的频率依赖性。方法　用标准微电极方法在不同基础周长 (BCL)时测定动作电位 ;采用全细胞膜片钳技术测定延迟整流钾电流 (IK:IKr、IKs)。结果　 10 0 μmol·L-1BTHP在BCL为 :2 0 0 0、2 5 0ms时 ,使APD2 0 分别延长 11 35 %和 2 5 5 5 % ;使APD90 分别延长15 97%和 32 5 6 %。 30 μmol·L-1BTHP在刺激频率为 :0 2 5和 2 0Hz时分别使Ikr,tial从 (0 94± 0 .44 ) pA·pF-1和(0 92± 0 31) pA·pF-1降至 (0 6 0± 0 32 ) pA·pF-1和 (0 43± 0 18)pA·pF-1。在刺激频率为 :0 1和 2 0Hz时分别使Iks,tial从 (4 2 2± 0 5 6 ) pA·pF-1和 (5 14± 0 2 8)降至 (2 5 8±0 41)pA·pF-1和 (2 6 2± 0 37)pA·pF-1。结论　BTHP可频率依赖性地阻滞IKr、IKs,其延长动作电位也呈频率依赖性     

药物相关性尖端扭转型室性心动过速性别差异的离子通道研究

目的　探讨药物相关性尖端扭转型室性心动过速 (TdP)发生率性别差异的离子流基础。方法　♀、♂兔各 2 0只 ,酶解法分得左室心尖部单个细胞 ,应用全细胞膜片钳技术记录APD、Ito、IK、IK1和ICa ,L。结果　♀、♂兔心肌细胞膜电容差异无显著性 (P >0 0 5 )。♀兔APD90 (5 6 0 4± 2 6 5ms,n =15 )比♂兔APD90 (489 0± 2 0 7)ms ,n =14长 (P <0 0 5 )。IK ,tail、Ito、IK1和ICa,L在♀兔分别为 (0 71± 0 0 5 )pA/ pF、n =17,(8 2 8± 1 0 3) pA/pF、n =18,(2 4 5± 3 6 ) pA/ pF、n =12 ,(9 0± 2 3)pA/ pF、n =15 ,在♂兔分别为 (0 84± 0 0 7) pA/pF、n =18,(8 6 0± 1 2 0 ) pA/pF、n =18,(2 5 9± 4 5 ) pA/pF、n =14 ,(9 3± 2 6 )pA/ pF、n =16。♀兔IK ,tail明显低于♂兔 (P <0 0 5 ) ,而Ito、IK1和ICa,L在♀、♂兔差异无显著性 (P >0 0 5 )。结论　♀兔IK ,tail较低可能是♀兔APD90 较♂兔长及更易发生药物相关性TdP的原因。     

长期应用西拉普利对血液透析病人心血管的保护作用

目的 :观察西拉普利对血液透析 (血透 )病人的心血管保护作用。方法 :70例血透病人分为治疗组 (n =36 ) ,用西拉普利 2 .5～ 5mg·d- 1和对照组(n =34) ,给予对心脏重构无影响的降压药。 6mo和 12mo时彩超测心脏指标 ,并测血透前后、血透次日血压。结果 :2组均有降压作用 ,治疗组等容舒张时间 (IRT)和左室重量指数 (LVMI)用药前及用药6 ,12mo分别为 (81±s 10 )ms ,(76± 10 )ms ,(6 9±10 )ms ,(2 18± 32 ) g·m- 2 ,(172± 30 ) g·m- 2 ,(15 3±32 ) g·m- 2 ;治疗后下降 (P <0 .0 5 )。左室射血分数(LVEF) ,心排量 (CO)和舒张早晚期速度比 (EV /AV)治疗前和用药 6 ,12mo分别为 (5 6 .2± 2 .1) % ,(6 0 .2± 1.8) % ,(74 .2± 1.6 ) % ;(5 .6± 1.2 )L·min- 1,(6 .3± 1.3)L·min- 1,(7.5± 1.5 )L·min- 1和 0 .91± 0 .0 4 ,1.0 1± 0 .0 4 ,1.2 1± 0 .0 3;治疗后升高 (P <0 .0 5 ) ,对照组无显著改变。结论 :长期应用西拉普利可有效降压、逆转血透病人的左室肥厚、改善左室舒缩功能     

甲基莲心碱对豚鼠心肌电—机械活动的影响

甲基莲心碱(Nef)0.1mM使豚鼠右心室乳头状肌的收缩力降低68. 3％,使动作电位APA和Vmax分别从112±5mV,240±37V/s降低到97±9 mV和86±25V/s;APD_(50),APD_(90)和ERP分别从173±23ms,205±17ms和201±16ms延长到201±26ms,239±28ms和249±23ms。Nef 1-200μM浓度依赖性地延长APD_(50),APD_(90)和ERP,降低Vmax和收缩力。30μM Nef能明显对抗10μM乙酰胆碱缩短豚鼠左心房APD的作用。结果提示,Nef对心肌Na~+,K~+,Ca~(2+)的跨膜转运均有抑制作用。     

异莲心碱对牵张性心律失常的作用

目的研究异莲心碱(isoliensinine,IL)对牵张性心律失常的拮抗效应.方法采用离体心脏心外膜心电图和在体心脏单相动作电位记录技术,观察膨胀大鼠左心室腔和结扎豚鼠升主动脉引起的心律失常、单相动作电位时程缩短和触发活动变化.结果IL(1,2.5,5μmol·L-1)能剂量依赖性地缩短膨胀引起的牵张性心律失常持续时间,从对照组的(2.18±0.28)s减少到(1.12±0.18)s,(0.75±0.14)s和(0.57±0.15)s.在麻醉豚鼠,静脉注射IL 2.5 mg·kg-1能够显著对抗结扎主动脉引起的50%和90%动作电位时程的缩短,从对照组水平的(94±7)ms和(112±8)ms延长至(114±8)ms和(128±8)ms;可减少触发活动的发生率,从对照组的(28.6±8.1)%减少到(6.5±4.6)%.结论IL具有拮抗牵张性心律失常作用,这种作用可能是通过阻断牵张活化的离子通道实现.     

Direct effects of esmolol and landiolol on cardiac function, coronary vasoactivity, and ventricular electrophysiology in guinea-pig hearts

The ultra-short acting, selective β(1)-adrenergic antagonists landiolol and esmolol are widely used perioperatively; however, little is known about their acute direct actions on the heart. The current study utilized the Langendorff perfused heart system to measure changes in cardiac function and hemodynamics in response to each drug. Furthermore, electrophysiological analysis was performed on isolated ventricular myocytes. Direct application of esmolol significantly decreased systolic left ventricular pressure and heart rate at concentrations > 10 μM, while it dose-dependently increased coronary perfusion pressure. Esmolol also shortened the action potential duration (APD) in a concentration-dependent manner, an action maintained even when the delayed rectifier K(+) current or ATP sensitive K(+) current was blocked. Moreover, esmolol inhibited both the inward rectifier K(+) current (I(K1)) and the L-type Ca(2+) current (I(CaL)) and increased the outward current dose-dependently. In contrast, landiolol had minimal cardiac effects. In the Kyoto Model computer simulation, inhibition of either I(K1) or I(CaL) alone failed to shorten the APD; however, an additional increase in the time-independent outward current caused shortening of the APD, equal to that induced by esmolol. In conclusion, esmolol directly inhibits cardiac performance significantly more so than landiolol, an effect revealed to be at least in part mediated by esmolol-induced APD shortening.     

Comparison of guinea-pig ventricular myocytes and dog Purkinje fibres for in vitro assessment of drug-induced delayed repolarization

INTRODUCTION: QT interval prolongation and Torsade de Pointes (TdP) arrhythmias are recognised as a potential risk with many drugs, most of which delay cardiac repolarization by inhibiting the rapidly activating K(+) current (I(Kr)). The objective of this study was to compare the effects of compounds on cardiac action potentials recorded from guinea-pig ventricular myocytes and dog Purkinje fibres. METHODS AND RESULTS: Effects of dofetilide, sotalol, cisapride, terfenadine, haloperidol and sparfloxacin, compounds known to cause QT prolongation (positive controls), and nifedipine and verapamil, not associated with QT prolongation (negative controls) were studied on intracellular action potentials recorded from guinea-pig isolated ventricular myocytes (VM) and dog isolated Purkinje fibres (PF). Prolongation of action potential duration (APD) by sotalol, dofetilide and sparfloxacin was concentration-dependent and of greater magnitude in dog PF compared to guinea-pig VM. The maximum prolongation of APD in guinea-pig VM at 0.5 and 1 Hz was approximately 25% and this was associated with complete inhibition of I(Kr) by dofetilide. Effects on APD of cisapride and haloperidol in both preparations, and terfenadine in guinea-pig VM, were biphasic, consistent with inhibition of multiple ion channels. There was no effect of terfenadine on APD in dog PF. Haloperidol increased APD by more than 25% in guinea-pig VM, consistent with effects on additional repolarizing currents. The negative controls shortened APD to a greater extent in guinea-pig VM compared to dog PF. In general, the positive control drugs increased action potential triangulation (APD(40-90)) to a greater extent than APD(90). CONCLUSION: Guinea-pig isolated VM may be more sensitive for detecting APD prolongation with compounds inhibiting multiple ion channels and action potential triangulation (APD(40-90)). Effects on repolarizing currents other than I(Kr) were also distinguished in guinea-pig VM.     

甲基苯丙胺对豚鼠心室肌细胞动作电位及延迟整流钾电流的影响(英文)

目的研究甲基苯丙胺对心血管系统的毒性作用及其机制。方法分离豚鼠心室肌细胞,采用全细胞膜片钳技术获取并分析心室肌细胞延迟整流钾电流(IK)及动作电位(AP)水平。结果甲基苯丙胺0.5mmol·L-1使豚鼠心室肌细胞AP幅值从121.6mV降至106.0mV,能延长动作电位时程(APD),但不改变静息电位水平。其中动作电位复极10%,25%,50%,75%及90%时程(APD10,APD25,APD50,APD75,APD90)分别延长179.0%,88.7%,47.7%,43.4%和31.9%(P<0.05)。甲基苯丙胺0.5mmol·L-1使快速激活延迟整流钾电流(IKr)和缓慢激活延迟整流钾电流(IKs)的膜电位水平降低,电流-电压曲线下移,但曲线形状不变,冲洗后能部分恢复。用含甲基苯丙胺0.01,0.1,0.5,1.0和3.0mmol·L-1的细胞外液分别灌流细胞5min,甲基苯丙胺对IKr尾电流幅度呈浓度依赖性的阻断作用,冲洗后能部分恢复。甲基苯丙胺对IKs尾电流的影响也非常显著(P<0.05)。结论甲基苯丙胺对豚鼠心室肌细胞的IK及AP都有不同程度的影响,这可能是甲基苯丙胺造成心脏损伤的电生理机制之一。     

An analysis of the stimulant effects of 5-hydroxytryptamine on isolated, blood-perfused rat heart.

In rat isolated hearts perfused at a fixed low rate, single injections of 5-hydroxytryptamine (5-HT) (0.1--3 microgram) into the coronary perfusion produced dose-dependent increases in left ventricular (LV) dP/dt max and perfusion pressure (PP), but no clear changes in heart rate. The increases in the LVdP/dt max and PP were not significantly affected by treatment with propranolol, while they were abolished by methysergide. The present study indicates that the positive inotropic and vasoconstrictor responses of the rat heart to 5-HT are not mediated by endogenous catecholamine release, but are induced by a direct action on 5-HT receptors.     

乌头碱与钾离子通道激动剂合用对离体大鼠心脏的正性肌力作用研究

目的　研究钾离子通道激动剂吡那地尔与乌头碱合用时乌头碱对心功能不全大鼠离体心脏的正性肌力作用。方法　本实验利用Langendorff离体心脏灌流装置 ,以左室收缩压 (LVSP)、左室压上升最大速率 ( +dp/dtmax)、左室压下降最大速率 ( -dp/dtmax)、左室舒张末压 (LVEDP)为指标 ,在①单纯使用乌头碱②乌头碱与吡那地尔 (KATP通道激动剂 )合用两种情况下 ,观察了乌头碱对腹主动脉狭窄法造成的心功能减退大鼠离体心脏的正性肌力作用。结果　实验结果表明①乌头碱对心功能不全大鼠离体心脏具有一定正性肌力作用 ,②乌头碱在激动钾通道的情况下 ,与单纯使用乌头碱相比 ,强心的有效浓度范围增大 ,强心效果明显增强 (P <0 0 5 )。结论　乌头碱对心功能减退的心脏具有强心作用 ,激动心肌钾通道可显著增强乌头碱的强心作用和有效浓度范围。     

Electrical and mechanical effects of anthopleurin-A, a polypeptide from a sea anemone, on isolated rabbit ventricular muscle under conditions of hypoxia and glucose-free medium

The effects of anthopleurin-A (AP-A, 1 x 10(-8) M) on the membrane action potential and contraction of isolated rabbit ventricular muscle were compared with those of ouabain (5 x 10(-7) M). Under control conditions, AP-A and ouabain showed submaximal (about 80% of maximal) positive inotropic effects without any toxic manifestations. AP-A caused a marked prolongation of action potential duration (APD) without affecting any other parameters of the action potential, whereas ouabain caused a shortening of APD and a slight decrease in maximum diastolic potential (MDP), overshoot (OS), and upstroke velocity (dV/dtmax) of the action potential. The positive inotropic effect of AP-A was relatively well maintained even under hypoxia or in glucose-free medium. Under these abnormal experimental conditions, AP-A caused a prolongation of APD only at the late stage of repolarization (APD80), whereas APD at the early stage of repolarization (APD30) was further shortened. Other parameters of action potential and resting tension (RT) were not influenced by AP-A. In contrast, under similar experimental conditions, ouabain caused no apparent positive inotropic action, but resulted in a marked increase in RT (contracture). In addition, after exposure to ouabain, a progressive shortening of APD and marked decreases in MDP, OS, and dV/dtmax were observed. These results indicate the AP-A has pharmacological properties quite different from those of ouabain and suggest possible advantages of this newly developed cardiotonic agent over cardiac glycosides when acting on the energy-depleted myocardium.     

Inotropic and chronotropic effect of glycerol formal on the isolated rabbit heart.

Glycerol formal (CAS 5464-28-8), an organic solvent used to vehicle drugs to target cells, has been shown to possess its own toxicopharmacological properties. The present work was undertaken to study its direct effect on the isolated rabbit heart. At 2.3 and 4.6 mmol/l (bolus) glycerol formal exerted a positive inotropic effect. Upon a perfusion of 4.5 mmol/l/h, the left ventricular pressure and the coronary flow were increased, while at 11 mmol/l/h these two parameters showed a tendency to decrease. Glycerol formal upon a perfusion at 11 mmol/l/h decreased mildly the positive inotropic effect of noradrenaline, and strongly that produced by acetylcholine at a nicotinic dose, while it accentuated the bradycardia induced by acetylcholine at a muscarinic dose. On the contrary it potentiated the stimulant effect of nicotine. The positive inotropic effects of tyramine, dimethylphenylpiperazinium and potassium chloride were decreased showing an inhibition of noradrenaline liberation induced by glycerol formal at the doses used. The action of glycerol formal on agents inducing a positive inotropic effect, except nicotine, and its cardiodepressant effect are probably partly due to its action on the Ca2+ ion.     

Obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.

The present study was designed to determine modulation of the direct inotropic effect of an anticholinesterase organophosphorus compound, phosphamidon, by the reactivator obidoxime. We investigated the effects of phosphamidon (n = 9), obidoxime (n = 5), and their combination (n = 5) on the mechanical and energetic indices of left ventricular function, in the isolated working rat heart model. Phosphamidon at a concentration range of 10(-6)-10(-3) M had a positive inotropic effect. Obidoxime at a concentration range of 10(-6)-10(-3) M had no significant effect on heart rate, but did have a statistically significant positive inotropic effect on end-systolic pressure, cardiac output, mean left ventricular pressure, and maximal time derivative of left ventricular pressure (dP/dtmax) (P less than 0.01). Perfusion with 10(-3) M obidoxime caused a 19% increase in left ventricular stroke work and a 31% increase in total pressure-volume area. Perfusion with phosphamidon and obidoxime at concentrations ranging from 10(-6) to 10(-3) M resulted in a more intense inotropic response than the separate drug effects. At the highest combined concentrations tested, cardiac output increased by 60%, left ventricular stroke work increased by 100%, and left ventricular total pressure volume area increased by 111% of their control values (P less than 0.001). We conclude that obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.     

Differential effects of OPC-18790, amrinone and dobutamine on cardiac function and energy metabolism in the guinea-pig isolated ischaemic heart.

1. The effects of OPC-18790, a novel positive inotropic agent, on cardiac function and myocardial energy metabolism in the guinea-pig isolated heart with ischaemia were studied by 31P-magnetic resonance spectroscopy (MRS) and compared with those of amrinone and dobutamine. 2. Cardiac ischaemia was induced by intracoronary infusion of 15 microns microspheres to reduce coronary perfusion flow (CPF) by 50%. Microsphere embolisation caused a 40% decrease in left ventricular systolic pressure (LVSP), cardiac contractility measured by peak of ventricular pressure development (LVdP/dt) and slightly reduced heart rate. There was also a decrease in ATP and creatine phosphate (PCr) by 20%, an increase in inorganic phosphate (Pi) by 25% and an acidic shift of intracellular pH in the ischaemic heart. 3. In the ischaemic heart, OPC-18790, amrinone and dobutamine were applied at concentrations which increased LVdP/dt by about 60%. These compounds increased LVP by 15% to 30% and increased CPF by about 10%. Amrinone and dobutamine but not OPC-18790 increased heart rate. When these drugs produced the haemodynamic changes described above, amrinone and dobutamine reduced ATP and PCr, increased Pi and produced further intracellular acidosis, whereas, OPC-18790 did not change these parameters. 4. Cardiac pacing at 285 beats min-1 produced decreases in LVP, LVdP/dt and CPF by about 30%, 20%, 5%, respectively and an increase in Pi, decreases in PCr and ATP, and intracellular acidosis. 5. These results suggest that degradation of high energy phosphate compounds closely relates to increase in heart rate in the ischaemic heart. Positive inotropic agents without chronotropic action seem to be beneficial in support of the ischaemic heart.     

Positive inotropic and blood pressure lowering activity of a diterpene derivative isolated from Coleus forskohli: Forskolin

Forskolin is a diterpene derivative isolated from the Indian plant Coleus forskohli. Forskolin has positive inotropic action on the isolated guinea pig heart, on the isolated left atrium of the guinea pig heart and on the dog and cat heart in situ. It increases the heart rate. The positive inotropic effect on the increase of heart rate are not blocked by beta-blockers. On reserpinized dogs the actions on the heart could also be seen. With high doses the action potential of the guinea pig papillary muscle is shortened. The positive inotropic effect could be differentiated from the effects of theophylline, cardiac glycosides and veratrine. Forskolin lowers the blood pressure in dogs and cats and also in spontaneously hypertensive and renal hypertensive rats.