茶色素对高钾状态下离体蟾蜍心脏活动的影响

目的探讨茶色素在高钾状态下对离体蟾蜍心肌收缩力、心率和心电图的影响。方法 60只蟾蜍随机分为对照组和实验组。对照组包括任氏液组、高钾(K~+浓度为1.14 mg/ml)模型组和阳性高钙(Ca~(2+)浓度为1.12 mg/ml)组;实验组为高钾任氏液+低、中和高剂量茶色素组(200、400、800μg/ml)。采用斯氏法制备离体蛙心灌流标本,应用BL-420F生物机能实验系统同时记录离体蟾蜍心肌收缩力和心电图曲线,进行心肌收缩力、心率和心电图的统计学分析。结果高钾模型组与任氏液组比较,离体蟾蜍的心肌收缩力、心率和心电图QRS峰值均明显减小(P<0.05),阳性高钙组与高钾模型组比较离体蟾蜍的心肌收缩力、心率和心电图QRS波峰值均明显增加(P<0.05);而高钾任氏液+低、中和高剂量茶色素组的心肌收缩力、心率和心电图QRS峰值与高钾模型组比较均显著增加(P<0.05),引起心肌收缩力、心率和心电图QRS峰值增加的最低浓度200μg/ml。结论茶色素能使高钾条件下心脏功能低下明显恢复。     

茶色素对心肌缺血离体蟾蜍心脏活动的预防作用

目的观察茶色素(TPs)预处理对心肌缺血离体蟾蜍心肌收缩力、心率和心电图的影响。方法选取50只蟾蜍随机分为对照组和实验组。对照组分为任氏液组和模型组。实验组分TPs预处理低、中和高剂量(200 mg/L、400 mg/L和800 mg/L)+垂体后叶素组。应用BL-420S生物机能实验系统同时记录离体蟾蜍心肌收缩力和心电图曲线,并进行心肌收缩力、心率和心电图的统计学分析。结果垂体后叶素组与任氏液组比较,心肌收缩力、心率和心电图QRS波峰值均明显减小(均P<0.05),心电图T波峰值明显增大(P<0.001)。灌流垂体后叶素与灌流不同浓度TPs比较:心肌收缩力,TPs为200 mg/L略有减小,差异无统计学意义(P>0.05),TPs为400 mg/L和800 mg/L时明显增加(P<0.05);心率略有变化,但差异无统计学意义(P>0.05);心电图,QRS波幅和T波峰值略有变化,差异无统计学意义(P>0.05)。结论一定浓度的TPs能预防由垂体后叶素引起的离体蟾蜍心脏活动低下。     

鹿茸对离体蟾蜍心肌保护作用的影响

目的观察鹿茸对离体蟾蜍心肌收缩力保护作用的影响。方法 90只蟾蜍随机分为对照组和实验组,实验组又分为异丙肾上腺素低钙组和异丙肾上腺素高钙组。采用斯氏法制备离体蛙心灌流标本,应用BL-420F生物机能实验系统记录的离体蟾蜍心肌收缩曲线,并进行心肌收缩力的统计学分析。结果在低钙条件下,灌流鹿茸溶液浓度为2 g/L时,心肌收缩力明显增加(P0.05);在高钙的条件下,灌流鹿茸溶液浓度为2 g/L时,心肌收缩力明显减弱(P0.05),并且鹿茸对离体蟾蜍心肌的收缩力具有保护的双向调节保护作用,不论在低钙条件下还是高钙的条件下均可部分使异丙肾上腺素(10 mg/L)兴奋(P0.01)。结论鹿茸对离体蟾蜍心肌收缩力具有双向调节保护作用,这种作用可能与心肌细胞膜上β受体兴奋有关。     

鹿茸的心肌收缩力保护作用与钙离子通道的相关性

目的观察鹿茸对离体蟾蜍心肌收缩的保护作用。方法 40只蟾蜍随机分为低钙组和高钙组,每一组又分为鹿茸前加维拉帕米组和鹿茸后加维拉帕米组。采用斯氏法制备离体蛙心灌流标本,应用B-420F生物机能实验系统记录离体蟾蜍心肌收缩曲线,并进行心肌收缩力的统计学分析。结果在低钙条件下,灌流鹿茸冻干粉溶液后心肌收缩力明显增加(P0.05);在高钙条件下,灌流鹿茸冻干粉溶液后心肌收缩力明显减弱(P0.05),且鹿茸的这种作用在低钙和高钙条件下可部分被维拉帕米(7.27 mg/L)阻断(P0.01)。结论鹿茸对离体蟾蜍心肌收缩力有双向调节保护作用,这种作用可能部分与心肌细胞膜上钙离子通道有关。     

阴离子替代和阴离子通道阻断剂对大鼠心率和心室收缩的影响

目的 :探讨 Cl-通道对大鼠离体心脏的心率和心室收缩的影响。方法 :采用离体心脏 Langendorff法灌流 ,监测心率和左心室内压的变化。结果 :通透性较弱的阴离子替代细胞外液中的 Cl-后 ,心率减慢和心室收缩减弱 ,Cl-通道阻断剂产生相似的结果。用高渗液灌流细胞后可以使室内压明显降低 ,但对心率的影响不明显。结论 :Cl-通道在维持心脏的功能活动中有调节作用     

柴胡皂苷d对离体蟾蜍心脏功能的影响

目的观察柴胡皂苷d对离体蛙心心率和心肌收缩力的影响。方法将60只健康蟾蜍分为空白对照组、不同浓度的柴胡皂苷d组(实验组)、维拉帕米组、维拉帕米+柴胡皂苷d组、艾司洛尔组、艾司洛尔+柴胡皂苷d组,每组10只,分别加入不同的药物;用BL-420生物机能实验系统测定每次给药后5 min内离体蛙心心肌收缩力及收缩频率的变化情况,记录蛙心心率和心力峰峰值,并采用变化率比较不同浓度柴胡皂苷d对正常离体蛙心心肌收缩力和心率的影响。结果不同终浓度的(0. 004 5、0. 009 0、0. 018 0 mmol/L)柴胡皂苷d对离体蛙心心率影响差异无统计学意义(P>0. 05),但可使离体蛙心的平均收缩力和心力峰峰值出现先逐渐上升、后逐渐下降;随着柴胡皂苷d浓度的增加,其对蛙心心力峰峰值的提高率逐渐升高,且有明显的药物浓度依赖性。柴胡皂苷d能够拮抗维拉帕米和艾司洛尔对离体蛙心心肌的抑制作用。结论柴胡皂苷d可使离体蛙心心肌收缩力先增强后减弱,其作用机制可能与激动心肌细胞上的β受体进而激活L型钙通道有关。     

钙预适应对膨胀离体大鼠心室所致心律失常的影响

为了证实钙预适应对膨胀离体大鼠心室所诱发的心律失常具有抑制作用 ,采用Langendorff方法灌流离体大鼠心脏。用正常灌流液灌流平衡后 ,离体心被随机分为 4组 :牵张对照组 ,钙预适应组 ,钙预适应 +维拉帕米组和钙预适应 +格列本脲组。维拉帕米和格列本脲在灌流液中的浓度分别为 1μmol/L和 10 μmol/L ,对钙预适应进行干预后及时用正常灌流液将他们从离体心洗脱。将可充灌液体的乳胶球囊通过左房及二尖瓣置于左室 ,通过向乳胶球囊注射液体对左室进行膨胀 ,记录膨胀前和膨胀过程中左室心电图和左室压力、冠脉流量和心率 ,观察心电图ST段和T波的变化 ,并计算对照组和各实验组由膨胀诱发心律失常的发生率和持续时间。结果 :通过乳胶球囊膨胀左室 ,使左室舒张末压增加相同的情况下 ,对照组心律失常总发生率达 10 0 % ,持续时间为 2 .5 6± 0 .4 6s ;钙预适应组较对照组心律失常总发生率明显降低 (40 % ) ,持续时间缩短到 1.6 7± 0 .6 1s(P均 <0 .0 5 ) ;用维拉帕米对钙预适应进行干预后 ,心律失常总发生率较钙预适应组增高 (90 % ) ,持续时间延长 (2 .5 0± 0 .4 6s) ;钙预适应 +格列本脲组心律失常发生情况和钙预适应组相似。各组离体心在膨胀前后冠脉流量和心率、心电图ST段和T波均未见明显变化。结论 :?     

天麻素在铁诱导的大鼠离体心肌损伤中的保护作用

目的观察天麻素在铁诱导的大鼠离体心肌损伤中的保护作用。方法应用Langendorff离体心脏灌流系统,灌注Fe-HQ建立铁诱导的离体心肌损伤模型。SD大鼠随机分成4组:正常组、Fe-HQ组、天麻素(0.1、0.025 mmol/L)组。观察天麻素对心率(HR)、左室收缩压(LVSP)、dp/dt max、冠脉流量(CF)的影响;测定冠脉流出液中的乳酸脱氢酶(LDH)及肌酸激酶(CK)的含量和心肌中丙二醛(MDA)的浓度;观察心肌组织的超微结构。结果天麻素能抑制铁诱导的心肌的HR、LVSP、dp/dt max、CF的下降;降低冠脉流出液中LDH和CK的含量及心肌中MDA的浓度。结论天麻素可改善铁诱导的心肌收缩功能和脂质过氧化,对铁诱导的大鼠离体心肌损伤有显著的保护作用。     

冠心灵对冠脉血流量、心肌收缩力和心电活动的影响

目的 :研究中药复方制剂冠心灵的心血管作用并初步探讨其作用机制。方法 :运用细胞内微电极技术、L angendorff离体心脏灌流和心率变异性功率谱分析等方法 ,研究冠心灵对心肌细胞动作电位的影响 ;观察其对冠脉血流量和心肌收缩力的作用 ;分析冠心灵对冠心病患者心率变异性的影响。结果 :冠心灵增强 Ca2 +跨膜内流 ;增加冠脉血流量和心肌收缩力 ;改善因缺血导致冠脉流量和心肌收缩力的下降 ;功率谱分析显示心迷走交感对心率的调控作用比升高。结论 :冠心灵有改善心肌缺血的作用。     

法舒地尔对大鼠离体心脏缺血/再灌注损伤的保护作用

目的观察盐酸法舒地尔对大鼠离体心脏缺血/再灌注（I/R）损伤是否有保护作用。方法SD大鼠19只,随机分为3组:I/R组、I/R+F组和对照组。用改良的Langendorff灌流装置,用K-H液行主动脉逆行灌流,建立大鼠离体心脏I/R损伤实验模型。I/R组预灌流20 min,停灌45 min,再灌30 min;I/R+F组于再灌注时在灌流液中加入盐酸法舒地尔注射液（10 mg/kg）;对照组连续灌流95 min。连续记录左心室收缩功能曲线,收集冠脉流出液,检测冠脉流出液中乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌红蛋白（Mb）漏出量以及心肌细胞内钙、心肌组织一氧化氮（NO）含量和髓过氧化物酶（MPO）活力。结果心肌缺血使冠脉流出量减少,LDH、CK、Mb增加,再灌注后冠脉流出量进一步减少,LDH、CK、Mb进一步增加,同时增加细胞内钙,增加MPO活力,减少NO生成。盐酸法舒地尔逆转再灌注后冠脉流出量减少和LDH、CK和Mb漏出增加,降低细胞内钙、MPO活力,逆转NO生成减少。I/R使左室发展峰压平均值、平均±dp/dtmax均下降,盐酸法舒地尔对左室发展峰压的改变无明显影响,但改善±dp/dtmax降低。结论盐酸法舒地尔对心肌I/R损伤有保护作用,增强I/R引起的"无复流"现象和心肌收缩能力降低的恢复,此作用与逆转NO生成减少、MPO活性增高和细胞内钙超载等因素有关。     

Dissociation between cardiac cyclic AMP and myocardial contractility induced by verapamil, calcium and magnesium ions.

Isolated, perfused rat hearts were used to study the effects of verapamil, excess calcium ions or excess magnesium ions on changes in heart cyclic AMP and myocardial force of contraction. Verapamil caused a dose-dependent decrease in force of contraction and a nondose-related reduction in cyclic AMP. Perfusion of hearts with medium containing 5 mM calcium produced a significant rise in cyclic AMP, but no change in contractile force. The depressant effects of verapamil on contractility and cyclic AMP were reversed by 5mM calcium; excess calcium in the perfusion fluid also containing verapamil prevented the myocardial depressant effects of verapamil. Acutely elevating the magnesium concentration in the perfusion medium decreased force of contraction, accentuated the negative inotropic effect of verapamil, but did not decrease cyclic AMP or enhance the verapamil-induced reduction in cyclic AMP.     

The negative inotropic effect of calcium overload in cardiac Purkinje fibers

The role of calcium in increasing or decreasing the force of contraction was studied in canine cardiac Purkinje fibers perfused in vitro under conditions known to alter cellular calcium. The following results were obtained: (1) increasing calcium load by perfusing a low Na solution increases contractile force in the presence of a low concentration of strophanthidin and decreases it in high strophanthidin; (2) decreasing calcium load by decreasing extracellular calcium leads to opposite effects; (3) the positive inotropic effect of low [Na]0 becomes negative in the presence of high [Ca]0; (4) high K decreases contractile force and reverses the negative inotropic effect of low Na in the presence of high strophanthidin; (5) a low Na-Ca solution increases initially the contractile force: high strophanthidin reverses the effect at normal K and exaggerates at high K, as apparently calcium overload is relieved by high K; (6) a low Na-Ca solution slowly removes calcium overload induced by high strophanthidin; (7) a low [Na]0 solution does not decrease force in the presence of high strophanthidin if extracellular calcium is also low; (8) the rebound increase in force is shifted to lower calcium concentrations after exposure to a low sodium solution with or without strophanthidin, as calcium overload becomes greater. It is concluded that in Purkinje fibers calcium overload induced by different means leads to a decrease in contractile force and that the force decline can be reversed by decreasing cellular calcium either during or after calcium overloading.     

Critical evaluation of isometric indexes of relaxation in rat and cat papillary muscles and toad ventricular strips

The effects of increasing calcium concentration and isoproterenol on myocardial relaxation were compared in cat and rat papillary muscles and toad ventricular strips. Isoproterenol effects were studied at equivalent positions of the calcium contractility response curve in the three species: at the plateau and at 25% and 50% of maximum. Calcium concentration was increased from the 25% point to the plateau of the calcium contractility curve for each species. Contractility was characterized by maximal velocity of tension development (+T). To study the relaxation phase, the following parameters were measured: maximal velocity of relaxation, (-T), the relationship between +T and -T (+T/-T), time to peak tension (TTP), time to half relaxation (t 1/2), relaxation time (Rt), total twitch duration (Tt) and the time constant of isometric tension decline from the time of -T (Tau). In rat muscles, t 1/2, Rt and Tt at all calcium levels, and Tau and +T/-T at the 50% and 100% of the calcium contractility curve, behaved as 'lusitropic': they significantly decreased with isoproterenol and not with calcium. Similar results were obtained in cat muscles except that at the 50% point of the calcium contractility curve, +T/-T was not significantly decreased. The behaviour of toad ventricle was different from that of mammalian heart: +T/-T and Tau appeared as lusitropic at all levels of the calcium curve, whereas only at the plateau some of the 'time' parameters were able to discriminate the isoproterenol lusitropic effect. These differences may reflect the strong dependence in amphibian heart of the time course of the action potential duration, not observed in mammalian ventricle.     

Effects of atrial natriuretic peptide and toad heart extract on isolated toad Bufo arenarum aortic rings.

The vascular effects of synthetic atrial natriuretic peptide (ANP) (rANP-99-126), and toad heart extract (THE) were examined on isolated toad aortic rings from the toad Bufo arenarum. ANP inhibited contraction produced by human angiotensin II (AT II), norepinephrine (NE), and arginine vasopressin (AVP) in isolated toad aortic rings. The present data show that a relaxant effect of ANP could be obtained also in the noncontracted aortic smooth muscle of toad if it had been previously challenged with AT II or NE and allowed to return to the original basal tension. Bufo arenarum THE was able to relax the AT II-induced contraction in toad aortic rings. In toad arteries contracted with 10(-6) M AT II, ANP produced a dose-dependent relaxation with a half-maximal inhibitory concentration IC50 of 1.2 x 10(-8) M. ANP was not effective in relaxing contraction induced by high K+. The vasorelaxant effect of ANP on AT II-induced contraction was significantly increased in Ca(2+)-free medium containing 3 mM ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA-Ringer) or by pretreatment with the calcium antagonist, diltiazem (DIL). The vasorelaxant effect of ANP on basal tension after treatment with AT II was also obtained in absence of extracellular calcium (EGTA-Ringer). These results show that Bufo arenarum contains ANP-like material and that the ANP relaxant action in the toad aorta is similar to that in mammals.     

Inotropic effect of thyrotropin-releasing hormone on the guinea pig myocardium

The inotropic effect of the physiological level of TRH on isolated guinea pig cardiac muscle was studied using a force transducer and standard microelectrode techniques. TRH increased the contractile force of muscles dose-dependently without changing the time course of contraction in normal Tyrode and a high K+ (27 mM) solution. The positive inotropic effect of TRH was associated with an augmentation of slow action potentials in high K+ solution and was reduced in the presence of diltiazem, verapamil, and manganese. TRH potentiated the response of contractile force to increasing extracellular Ca2+ concentration. The inotropic effect of TRH was suppressed by metoclopramide, phentolamine, and cimetidine, but was not affected by propranolol. TRH increased the contractile force even in the myocardium of reserpinized guinea pig. It is suggested that TRH has a positive inotropic effect at least partly due to an increase in the slow inward Ca2+ current.     

Relationship between cardiac contractility and energy supply to the heart

When nicotinic acid was given intraperitoneally to rats, there was a marked decrease in the ventricular force of contraction and in the inotropic response to 1-norepinephrine at 2 and 4 hours after administration of the drug; 6 hours after the injection of nicotinic acid, myocardial contractility had returned to normal. Severe impairment in cardiac contractility coincided with the period when heart triglycerides and myocardial glycogen were depleted by the nicotinic acid. Inclusion of oleic acid, triglyceride, or glucose in the medium perfusing the heart restored normal contractility and the inotropic response to 1-norepinephrine. Results of these experiments indicate a direct relationship between myocardial contractility and the availability of energy-supplying substrates.     

人参二醇组皂甙在抗心肌缺血再灌注损伤作用中的钙拮抗剂效应

目的研究适宜浓度的人参二醇组皂甙(Panaxadiol Sapanins,PDS)在抗心肌缺血再灌注损伤作用中的钙拮抗剂效应。方法大耳白兔30只,体重(2.5±0.3)kg,随机分为对照组与4个实验组,每组6只,制成离体作功兔心模型。St.Thomas心脏停搏液用于对照组,该停搏液内分别加入浓度为40、80、160、320mg/L的PDS用于4个实验组(以PDS 40 mg/L组、PDS 80 mg/L组、PDS 160 mg/L组、PDS 320 mg/L组表示)。在阻断升主动脉即刻和心脏停搏30min、60min时分别灌注心脏停搏液。于心脏停搏前10min和心脏复搏后心脏作功30min时取心肌标本测定心肌钙离子含量。结果再灌注后PDS 40 mg/L组、PDS 80 mg/L组、PDS 160 mg/L组三个实验组的心肌钙离子含量均明显低于对照组(P<0.05或P<0.01),尤以PDS 160mg/L为著。而PDS 320mg/L组的心肌钙离子含量与对照组无显著差异(P>0.05),甚至有增高倾向。结论在抗心肌缺血再灌注损伤作用中,作为心脏停搏液的添加剂,PDS在40~160mg/L的浓度范围,有钙拮抗剂样作用,且在一定范围内随着浓度递增,该作用增强。但当PDS浓度增至320mg/L时,钙拮抗剂样作用消失。     

Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats

Background

One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes).

Objective

This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats.

Method

In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µg.kg^-1.day^-1, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage.

Results

Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively).

Conclusion

The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.     

Sources of calcium in agonist-induced contraction of rat distal colon smooth muscle in vitro

AIM： To study the origin of calcium necessary for agonist-induced contraction of the distal colon in rats.METHODS： The change in intracellular calcium concentration （[Ca^2＋]i） evoked by elevating external Ca^2＋ was detected by fura 2/AM fluorescence. Contractile activity was measured with a force displacement transducer. Tension was continuously monitored and recorded using a Powerlab 4/25T data acquisition system with an ML110 bridge bioelectric physiographic amplifier.RESULTS： Store depletion induced Ca^2＋ influx had an effect on [Ca^2＋]i. In nominally Ca^2＋-free medium, the sarco-endoplasmic reticulum Ca^2＋-ATPase inhibitor thapsigargin （1 μmol/L） increased [Ca^2＋]i from 68 to 241 nmol/L, and to 458 （P 〈 0.01） and 1006 nmol/L （P 〈 0.01）, respectively, when 1.5 mmol/L and 3.0 mmol/L extracellular Ca^2＋ was reintroduced. Furthermore, the change in [Ca^2＋]i was observed with verapamil （5 μmol/L）, La3＋ （1 mmol/L） or KCl （40 mmol/L） in the bathing solution. These channels were sensitive to La3＋ （P 〈 0.01）, insensitive to verapamil, and voltage independent. In isolated distal colons we found that in normal Krebs solution, contraction induced by acetylcholine （ACh） was partially inhibited by verapamil, and the inhibitory rate was 41% （P 〈 0.05）. On the other hand, in Ca^2＋-free Krebs solution, ACh induced transient contraction due to Ca^2＋ release from the intracellular stores. The transient contraction lasted until the Ca^2＋ store was depleted. Restoration of extracellular Ca^2＋ in the presence of atropine produced contraction, mainly due to Ca^2＋ influx. Such contraction was not inhibited by verapamil, but was decreased by La3＋ （50 μmol/L） from 0.96 to 0.72 g （P 〈 0.01）. CONCLUSION： The predominant source of activator Ca^2＋ for the contractile response to agonist is extracellular Ca^2＋, and intracellular Ca^2＋ has little role to play in mediating excitation-contraction coupling by agonists in rat distal colo     

Physiological and pathophysiological modulation of calcium signaling in myocardial cells.

The relationship between changes in intracellular Ca2+ transients and isometric contractions has been assessed in intact cardiac muscle preparations, superficial cells of which have been microinjected with the Ca(2+)-sensitive bioluminescent protein aequorin. Regulation of myocardial contractility by physiological and pathophysiological intervention is achieved by either (1) modulation of intracellular Ca2+ mobilization, or (2) modulation of Ca2+ sensitivity of myofibrils, or both. Regulation of contractility by changes in heart rate a well established frequency-force relationship that plays an important role in the cardiac pumping function in situ is mainly achieved by mechanism (1), other mechanisms becoming involved depending on the range of frequency of stimulation. The length-dependent regulation of contractility (length-tension relationship in vitro or Frank-Starling's law, or ventricular function curve in situ) is achieved essentially by mechanism (2). Catecholamines promote mechanism (1) through activation of beta- and/or alpha-adrenoceptors, alpha-adrenoceptor stimulation being much less effective than beta-stimulation in this respect. beta-Adrenoceptor stimulation decreases, while alpha-stimulation may increase the Ca(2+)-sensitivity of contractile proteins. Subsequent to exposure of muscle preparations to Ca2+ free solution, a prominent and reversible dissociation of force of contraction from Ca2+ transients was produced when the [Ca2+]0 was gradually returned to the level of the normal Krebs-Henseleit solution [( Ca2+]0 = 2.5 mM). The aequorin-injected multicellular intact myocardial cell preparation provides an excellent experimental paradigm through which to address the physiological, pharmacological and pathophysiological modulation of E-C coupling in mammalian cardiac muscle. The subcellular mechanism involved, especially in the pathophysiological modulation of Ca2+ signaling process in myocardial cells, awaits further study.