The effect of isoproterenol on phospholamban-deficient mouse hearts with altered thyroid conditions.

The aim of the present study was to determine the effects of beta -adrenergic stimulation in wild-type and phospholamban-deficient mouse hearts with altered thyroid conditions. Hypothyroidism was associated with significant decreases in heart/body weight ratio in wild-type and phospholamban-deficient mice, whereas hyperthyroidism was associated with significant increases in heart/body weight ratio in both groups. Hypothyroid hearts of wild-type and phospholamban-deficient mice exhibited similar increases in beta -myosin heavy chain protein levels and decreases in alpha -myosin heavy chain protein levels. In hyperthyroidism, there were increases in the alpha -myosin heavy chain protein levels and these were similar in wild-type and phospholamban-deficient hearts. There were no detectable levels of beta -myosin heavy chain protein in the hyperthyroid hearts. The relative tissue level of phospholamban in wild-type hearts was increased (133%, P<0.01) in hypothyroidism, and decreased (69%, P<0.01) in hyperthyroidism, when compared to euthyroid controls (100%). Similar increases and decreases in SR Ca(2+)-ATPase protein levels were observed between phospholamban-deficient and wild-type hearts in hyperthyroidism and hypothyroidism, respectively. The basal contractile state of wild-type and phospholamban-deficient hearts was significantly depressed in hypothyroidism. On the other hand, the basal contractile state of wild-type and phospholamban-deficient hearts was significantly increased in hyperthyroidism. During beta -agonist stimulation of wild-type hearts, the responses in the rates of contraction and relaxation were highest in the hypothyroid group, followed by the euthyroid, and lastly by the hyperthyroid groups. There was a close linear correlation between the magnitude of the contractile parameter responses and the phospholamban/SERCA2 ratios in these hearts. However, the phospholamban-deficient hypothyroid, euthyroid, and hyperthyroid hearts did not exhibit any responses to isoproterenol, indicating that the alterations in the thyroid states of these hearts do not influence the effects of isoproterenol on cardiac function. These findings suggest that phospholamban is an important regulator of the heart's responses to beta -adrenergic stimulation under various thyroid states.     

Experimental hyperthyroidism II mechanics of contraction and relaxation of isolated ventricular myocardium

The effect of experimental hyperthyroidism on myocardial mechanics was examined on isolated ventricular myocardium (right ventricular papillary muscle) of cats. 1. Isotonic muscle contraction and isometric tension development were largely unchanged compared with euthyroidism. 2. Isotonic contraction velocity and maximal isometric tension rise velocity showed considerable rises of between 41 and 78%. 3. Force-velocity relations of contraction showed changes with increases of contraction velocity with every degree of load. 4. Force-velocity relations of isotonic relaxation showed increases of isotonic relaxation maxima with comparable loads without any alteration of the typical course of the relaxation curves compared with euthyroidism. 5. Lowering the temperature (from 34 to 24 degrees C) produced a considerable fall of the raised contraction and relaxation velocity in hyperthyroidism whereas the values of muscle contraction and tension development important for the pump function were largely unchanged. It is concluded that the myocardium in experimental hyperthyroidism is characterised by a primarily velocity-related increase of inotropy. Lowering the temperature produces an effective fall of the raised velocity values. The mechanisms of the increase of inotropy and significance of the findings are discussed.     

多巴酚丁胺对冬眠心肌灌注,代谢及功能的影响及其临床意义

目的 探讨多巴酚丁胺负荷试验（ＤＳＴ）对冬眠心肌灌注、代谢和功能的影响及其临床意义。方法 结扎猪冠状动脉左前降支制作心肌冬眠模型。２０只猪在冠状动脉结扎前的非缺血阶段作用对照组。然后按缺血程度分成中度和重度缺血的心肌冬眠分别为甲组和乙组,每组各１０只。采用ＤＳＴ“唤醒冬眠心肌,测量各试验阶段心肌灌注（ＭＢＦ）、代谢（ＭＶＯ２、ＱＬａｃ、ｐＨｖ）、收缩功能（ＷＴ）及血流动力学（ＲＰＰ）指标,比较组仙     

极化液与参松养心胶囊在治疗室性早搏中的作用

目的：对比观察极化液（氯化钾＋胰岛素＋葡萄糖）和参松养心胶囊治疗室性早搏的疗效和不良反应。方法：124例室性早搏病例被随机分为极化液组（62例）和参松组（62例）,极化液组给予极化液和美托洛尔治疗,参松组给予参松养心胶囊并美托洛尔治疗,治疗2周后,观察两组室性早搏发作以及不良反应的情况。结果：治疗2周后,参松组控制室性早搏有效率明显优于极化液组（88.71%∶67.7%,P〈0.05）,出现的不良反应也明显少于极化液组（1.6%∶11.3%,P〈0.05）。结论：参松养心胶囊治疗室性早搏的效果较极化液好,且不良反应少。     

心脏右侧DDD起搏对心功能和心室收缩同步性的影响

目的 用平衡法核素心室显像（equilibrium　radionuclide　angiography,ERNA）方法评价心脏右侧DDD起搏对心功能和心室同步性的影响。方法10例病态窦房结综合征或间歇二度房室阻滞患者植入DDD起搏器。患者植入起搏器后行ERNA检查,用程控仪调整起搏器参数,分别在起搏情况下和窦性心律情况下采集数据,通过半自动处理数据获得心功能参数,对采集的数据进行位相分析（Phase analysis）处理,了解心室激动顺序,计算出相角程（Phase　shift）来评估心室激动的同步性。结果患者在起搏时,左心室1/3EF比窦性心律时明显减低[（0.23±0.06）对（0.28±0.05）,P=0.01]。位相分析显示起搏时右心室激动早于左心室,相角程增宽[（64.13±16.81）°对（52.88±9.26）°,P=0.007]。在窦性心律时心室激动顺序为从室间隔近端或左心室基底部向心尖方向扩散,起搏心律时心室激动顺序发生改变,从右心室心尖部向心底部和左心室扩散。结论 单纯右心室起搏增加心室不同步性,影响左心室收缩功能。     

Effects of hypokalemia on transmural dispersion of ventricular repolarization in left ventricular myocardium

ObjectiveTo observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit, and explore the role of hypokalemia in malignant ventricular arrhythmia (MVA).MethodsA total of 20 rabbits were randomly divided into control group and hypokalemic group. Isolated hearts in the control group were simply perfused with modified Tyrode's solution, and were perfused with hypokalemic Tyrode's solution in hypokalemic group. Ventricular fibrillation threshold (VFT), 90% monophasic action potential repolarization duration (APD₉₀) of subepicardial, midmyocardial and subendocardial myocardium, transmural dispersion of repolarization (TDR) and C×43 protein expression in three layers of myocardium were measured in both groups.ResultsVFT in the control group and the hypokalemic group were (13.40±2.95) V, and (7.00±1.49) V, respectively. There was a significant difference between two groups (P<0.01). APD₉₀ of three myocardial layers in the hypokalemic group were significantly prolonged than those in the control group (P<0.01). ΔAPD₉₀ in the hypokalemic group and the control group were (38.10±10.29) ms and (23.70±5.68) ms, and TDR were (52.90±14.55) ms and (36.10±12.44) ms, respectively. ΔAPD₉₀ and TDR in the hypokalemic group were significantly higher than those in the control group (P<0.05), and the increase in APD₉₀ of midmyocardium was more significant in the hypokalemic group. Cx43 protein expression of all three myocardial layers were decreased significantly in the hypokalemic group (P<0.01), and ΔCx43 was significantly increased (P<0.05). Reduction of Cx43 protein expression was more significant in the midmyocardium.ConclusionsHypokalemic can increase transmural heterogeneity of C×43 expression and repolarization in left ventricular myocardium of rabbit, and decrease VFT and can induce MVA more easily.     

Uniformity of calcium channel number and isometric contraction in human right and left ventricular myocardium

Summary We compared contractile performance in trabeculae carneae (n=25) from non-failing right and left ventricles (n=25) of brain dead organ donors without known cardiovascular disease and measured connective tissue content in trabeculae carneae from both non-failing and failing human hearts. Peak twitch force and time-course of contraction were not different between muscles taken from right or left ventricles. Peak twitch force was 13.9±3 vs. 13.7±2.7 mN/mm² for right and left ventricular trabeculae carneae, respectively in 2.5 mM [Ca²⁺]₀ at a 0.33 Hz stimulation frequency. Time to peak tension (405±21 vs. 405±12 ms), time to 50% relaxation from peak contractile response (277±21 vs. 278±14.6 ms) and time to 80% relaxation (428±29 vs. 433±22) were not different between right and left ventricular trabeculae carneae. Calcium channel number determined by [³H]PN200-100 dihydropyridine-radioligand binding assay was also not different (56.2±6.5 fmol/mg protein vs. 58.6±8.4 fmol/mg protein for right and left heart preparations, respectively). However, in myocardium obtained from ischemic hearts the left ventricle showed a reduced number of calcium channels compared to the right ventricle (55.3±3.8 vs. 36.6±3.9 fmol/mg protein for right and left ventricle, respectively p=0.027). No differences were noted in the number of DHP receptor binding sites between right and left ventricular myocardium from patients with idiopathic dilated cardiomyopathy (51.4±7.6 fmol/mg protein vs. 61.8±6.5 fmol/mg protein respectively). Our data indicate that calcium channel number is similar for non-failing left and right human ventricle. Contractile response to changes in [Ca²⁺]₀ and frequency were similar for trabeculae carneae from the left and right ventricles of non-failing human hearts. Studies involving calcium channel activation or inhibition in ischemic human myocardium, where there may be differences in calcium channel number and/or function are warranted. Whether changes in calcium channel number have biological consequences on contractile function remains to be determined. Importantly, careful studies of calcium channel function underin vivo conditions are warranted.Work supported in part by a grant from Glaxo Inc to JKG and the Institute for the Study of the Treatments of Cardiovascular Diseases, Cardiovascular Drug Development and Marketing Consultants, and HL-39091 and HL-36797 to JKG. HL 31117 to JPM. EJG is a fellow of the Stanley J. Sarnoff Society of Fellows for Research in Cardiovascular Science. JKG is an Established Investigator of the American Heart Association.     

右心室流出道与右心室心尖部起搏对心室收缩同步性和心功能的影响

目的研究右心室流出道(right ventricular outflow tract,RVOT)间隔部和右心室心尖部(right ventricularapex,RVA)起搏对心脏收缩同步性、收缩功能的影响,探讨RVOT间隔部起搏的意义。方法 50例病态窦房结综合征患者分为RVOT组(n=25)和RVA组(n=25),起搏器置入1个月后通过调整房室间期使心室节律全部为起搏节律或房室结自身下传节律,观察起搏参数,并行超声心动图检查。结果RVOT组与RVA组电极导线植入时间、X线曝光时间比较,差异无统计学意义(P>0.05)。全部患者未出现植入并发症。两组随访1个月时起搏参数比较,差异无统计学意义(P>0.05)。RVOT组和RVA组起搏后的QRS波时限较前明显增宽,差异有统计学意义[RVOT组:(135±8)ms vs.(88±8)ms,P<0.001;RVA组:(154±8)ms vs.(90±6)ms,P<0.001]。RVA组起搏后QRS波时限较RVOT组增宽更为明显,差异有统计学意义(P<0.001)。两组起搏后室间机械延迟(interventricularmechanical delay,IVMD)和室间隔-左心室后壁收缩运动延迟时间(septal-to-posteriowall motion delay,SPWMD)较起搏前均显著增加,差异有统计学意义(P<0.001)。RVA组起搏后IVMD和SPWMD绝对值较RVOT组显著延长,差异有统计学意义[IVMD:(38±7)ms vs.(24±5)ms,P<0.001;SPWMD:(118±21)ms vs.(60±11)ms,P<0.001]。两组左心室舒张末内径及左心室射血分数比较,差异无统计学意义(P>0.05)。结论右心室起搏会造成心室收缩不同步,RVOT起搏对心室收缩不同步的影响较RVA起搏小,提示RVOT起搏是较为生理的起搏位点。     

NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes

Since aging increases oxidative stress, we analyzed the contribution of reactive oxygen species (ROS) to the contractile dysfunction of aged ventricular myocytes and investigated whether short-term interference with ROS formation could normalize contractile performance.     

Effects of cellular uncoupling on conduction in anisotropic canine ventricular myocardium

Experiments were performed on canine superfused ventricular epicardial tissue slices to determine the effects of 1.0-2.0 mM heptanol, an uncoupling agent, on conduction longitudinal and transverse to myocardial fiber orientation. Conduction velocities were measured between proximal and distal pairs of epicardial electrodes oriented transverse and longitudinal to the direction of a conducted wavefront evoked by pacing at a basic cycle length of 2,000 msec from one margin of the tissue before and after the addition of heptanol. In a separate group of tissues, the dual bipolar orthogonal electrode was used to sequentially map epicardial activation at 40 to 45 sites in a 1 cm x 2 cm area before and 30 minutes after the introduction of heptanol. In a third group of tissues, transmembrane potentials were recorded with standard microelectrode techniques to determine the effects of heptanol on action potential characteristics. Heptanol did not significantly effect action potential amplitude or maximum rate of depolarization. After 1.0 mM heptanol, conduction velocity began to decrease in 1-2 minutes and reached a steady state in 15-20 minutes. Conduction velocity in the longitudinal direction decreased from a control value of 0.56 +/- 0.13 to 0.46 +/- 0.10 M/sec (+/- SD) at 30 minutes after heptanol (p = 0.005). In the transverse direction, it decreased from 0.24 +/- 0.09 to 0.17 +/- 0.05 M/sec (p = 0.002). The ratio of longitudinal to transverse conduction velocities increased from 2.54 +/- 1.00 to 2.94 +/- 0.82 (p = 0.042). Thus, heptanol preferentially slowed conduction in the transverse direction. Because heptanol did not greatly influence active membrane properties, we used cable equations to calculate the time course of the change in effective junctional resistivity, which rose from 133.2 omega.cm before heptanol to 312.2 omega.cm 30 minutes after heptanol administration. We conclude that heptanol slows conduction velocity by selectively increasing junctional resistivity. The preferential slowing of conduction in the transverse direction is most likely due to the fact that more junctional resistances are encountered per unit distance in the transverse than in the longitudinal direction.     

Differences in the electrophysiological response of canine ventricular subendocardium and subepicardium to acetylcholine and isoproterenol. A direct effect of acetylcholine in ventricular myocardium

A prolongation of the ventricular effective refractory period in response to cholinergic agonists or vagal stimulation has been demonstrated in a number of in vivo animal models. However, exposure of isolated myocardial tissues obtained from these hearts to as much as 10(-4) M acetylcholine has been shown to produce essentially no change in action potential duration or effective refractory period. The discrepancy between the in vivo and in vitro findings generally has been explained on the basis of accentuated antagonism, whereby parasympathetic agonists exert their influence through antagonism of the effects of beta-adrenergic tone in vivo. The fact that acetylcholine exerts little if any direct effect on the electrical activity of ventricular myocardium, although well accepted, is based exclusively on studies performed using endocardial preparations. Our recent demonstration of major electrophysiological differences between canine ventricular endocardium and epicardium prompted us to examine the effects of acetylcholine and the role of accentuated antagonism in these two tissue types. Using standard microelectrode techniques, we show that acetylcholine (10(-7)-10(-5) M) has little if any effect in canine ventricular endocardium but a pronounced effect to either prolong or markedly abbreviate action potential duration and effective refractory period in epicardium. These effects of acetylcholine on epicardium are attended by an accentuation of the spike and dome morphology of the action potential, are readily reversed with atropine, fail to appear when epicardium is pretreated with the transient outward current blocker 4-aminopyridine, are accentuated in the presence of isoproterenol (10(-7) to 5 x 10(-6) M), and persist in the presence of propranolol. Isoproterenol-induced abbreviation of action potential duration and effective refractory period is also shown to be more pronounced in epicardium than in endocardium; equimolar concentrations of acetylcholine completely antagonize the effects of isoproterenol in endocardium and epicardium. We conclude that acetylcholine exerts important direct effects on the electrical response of canine ventricular myocardium, which are accentuated in the presence of beta-adrenergic agonists. Our findings suggest the differential response of epicardium and endocardium to acetylcholine is due to the presence of a transient outward current-mediated spike and dome morphology in the epicardial action potential. Finally, the data suggest that acetylcholine may exert antiarrhythmic as well as arrhythmogenic effects through its actions to alter conduction and refractoriness.     

Effects of reperfusion on the regional contraction of ischemic and nonischemic myocardium following partial coronary obstruction

In 14 dogs the effects on regional tension (Walton-Brodie gauges) and length (mercury-in-silastic) following 50% reduction (52.9 +/- 2.1) in coronary flow for two hours and reperfusion afterwards for one hour were addressed. Within five minutes of partial coronary occlusion, ejection tension in the ischemic zone decreased to 36.3 +/- 7.2% (P less than 0.001) and total tension to 64.4 +/- 5.7% of control (P less than 0.001) while phasic segment length increased to 165.2 +/- 16.3% control. No further significant changes in regional tension or length were observed throughout the two hour period of partial occlusion. Ejection tension remained positive and segment length maintained systolic shortening during the ejection phase throughout the period of occlusion. Following reperfusion, ejection tension in the ischemic zone increased from 35.1 +/- 5.9 to 87.0 +/- 22.0% (P less than 0.05) and total tension increased from 56.6 +/- 5.4 to 70.2 +/- 7.2% (P less than 0.02) while segment length decreased from 149.3 +/- 6.5 to 105.7 +/- 5.7% (P less than 0.001) within five to 15 min of reperfusion. The improvement in both regional tension development and segment length shortening was maintained throughout the one hour period of reperfusion. No significant changes were seen in the nonischemic zone. The present experimental study suggests that partial coronary occlusion producing a 50% reduction in coronary blood flow results in regional contractile changes. These changes are reversible at least twice as long as those following complete occlusion.     

缝隙连接对心肌肥厚兔室性心律失常的影响

目的研究兔慢性压力超负荷模型中缝隙连接(G J)对室性心律失常的影响。方法30只兔随机分为假手术组(Sham组)、心肌肥厚组(LVH组)和抗心律失常肽组(AAP10组)。LVH组和AAP10组通过缩窄腹主动脉制备兔左室压力超负荷心肌肥厚模型,Sham组仅游离腹主动脉未进行缩窄。动物饲养3个月后制备兔左室楔形心肌块的灌注模型,Sham组和LVH组灌流台氏液,AAP10组灌流含AAP10的台氏液,记录不同起搏周长下容积心电图、跨室壁离散度(TDR)及刺激反应间期(SR I),并观察早期后除极(EAD)及室性心律失常的发生率。结果在不同频率起搏下,LVH组SR I和TDR与Sham组比较均明显增加(P<0.05)。而AAP10组的SR I和TDR与LVH组比较明显减小(P<0.05)。Sham组无1例诱发EAD和室性心律失常;在5 000 m s起搏时LVH组和AAP10组EAD的发生率分别为10/10、3/10,室性心律失常发生率分别为4/10,1/10,两组比较差异有显著性(P<0.05)。结论G J激动剂AAP10减轻了心肌肥厚时SR I的延长和TDR增加,相应的减少了EAD和室性心律失常的发生率。     

Effects of activation sequence on ventricular refractory periods of ischemic canine myocardium

Refractory periods were measured in pentobarbital-anesthetized dogs during control periods and one to one and a half hours after distal left anterior descending coronary artery occlusion. The refractory period test site was on the anterior surface of the left ventricle in the distribution of the artery to be occluded. Measurements were made during drive of the refractory period test site, drive of a distant site on the pulmonary conus and during fusion drive in which drive of the test site was delayed with respect to drive of the pulmonary conus. Refractory periods were longer during test site drive than during pulmonary conus or fusion drives in both the control periods and following coronary occlusion. However, the effects of driving mode on refractory periods were greater following coronary occlusion than in the control periods. The findings are likely secondary to different magnitudes of change in electrotonic interactions associated with changes in activation sequence in ischemic and nonischemic myocardium. The greater dependence of repolarization properties in ischemic than nonischemic tissue suggests that inhomogeneity of these properties could be modified considerably by the site of origin of ectopic ventricular complexes.