快速右心室起搏致充血性心力衰竭犬心肌组织内皮素系统的表达变化

本研究在快速起搏致心力衰竭模型中利用起搏持续时间的差异而建立不同严重程度的心力衰竭模型 ,研究充血性心力衰竭中心肌组织内皮素系统的变化规律。一、材料与方法1.心力衰竭模型 :3 5只成年杂种犬 ,随机分为 5组 ,每组7只。戊巴比妥钠腹腔内麻醉 ,植入心脏起搏装置 ,2 4 0次 /ｍｉｎ固定频率快速起搏右心室。 4组犬分别起搏 1、2、3及 4周后、对照组行假手术 4周后 ,测定血流动力学参数并取左心室游离壁心肌组织。2 .ＲＴ ＰＣＲ检测目的基因表达水平 :根据已报道的内皮素前体原 (ｐｐＥＴ)、内皮素Ａ受体 (ＥＴＡ)和内皮素Ｂ受体(ＥＴＢ…     

超声心动图在评估犬慢性心力衰竭模型中的作用

目的探讨超声心动图在评估犬慢性心力衰竭模型中的作用。方法对10只比格犬进行快速右心室起搏,起搏前及起搏4周停止起搏后进行多普勒超声心动图和血流动力学检查。结果快速右心室起搏4周后,所有犬都出现气促、四肢浮肿等情况,并有不同程度的胸、腹腔积液。超声心动图示左室EF、FS较起搏前显著降低（P<0.01）,分别为（0.63±0.05）vs（0.42±0.10）和（0.33±4.50）vs（0.19±6.19）;血流动力学检测示犬左室±dp/dtm ax较起搏前均显著降低（P<0.01）,分别为[（9846±415）vs（3330±307）mmHg/s]和[（-7925±3558）vs（-2260±113）mmHg/s]。起搏前后犬左室EF和FS值与+dp/dtm ax值呈良好的正相关（P<0.01）。结论通过超声心动图和血流动力学指标的相关性分析,表明超声心动图在评价心力衰竭动物模型上是无创、便捷、重复性好的方法。     

快速右心室起搏致充血性心力衰竭犬可控性动物模型的建立

目的 建立不同严重程度的心力衰竭动物模型。方法 35只犬随机分为5组,分别接受假手术,快速右心室起搏1周、2周、3周和4周,通过动物心衰症状的轻重和血液动力学指标评价心力衰竭的严重程度,RIA法测定血浆内皮素浓度。结果 随着起搏时间的延长,动物逐渐出现相应的症状,血液动力学参数显示心力衰竭严重程度逐步增加,血浆内皮素浓度逐渐上升并与心力衰竭严重程度明显相关。结论 快速起搏致充血性心力衰竭犬模型在病程上具有可控性的优点,是一种较为理想研究充血性心力衰竭的实验模型。     

心力衰竭犬血小板功能及血浆血管性血友病因子、内皮素-1改变的实验研究

目的:观察慢性心力衰竭犬血小板聚集功能和血浆血管性血友病因子(vWF)、内皮素-1(ET-1)和血管紧张素Ⅱ(AngⅡ)含量的变化,探讨心力衰竭血栓前状态的形成机制.方法:14只犬随机分为起搏组(8只)和假手术组(6只),起搏组犬植入实验用心室非同步固定频率起搏方式(VOO)型起搏器,行心室快速起搏(220次/分)6周,建立心力衰竭犬模型.起搏组犬于起搏前和起搏后6周,假手术组犬于术前和术后7周采静脉血测定血小板最大聚集率及血浆vWF、ET-1和AngⅡ含量.结果:①假手术组犬术前与术后7周比较,心脏功能、血小板最大聚集率及血浆vWF、ET-1、AngⅡ含量均无明显变化.②快速心室起搏后6周,起搏组所有犬出现心功能不全症状,心脏每搏量、心输出量、左心室射血分数及心脏指数较起搏前明显降低,有显著性差异(P＜0.05～0.01);③起搏组犬快速心室起搏后6周,由二磷酸腺苷、肾上腺素、胶原和花生四烯酸诱导的血小板最大聚集率较起搏前增加,有极显著性差异(P＜0.01);④快速心室起搏后6周,起搏组犬血浆vWF、ET-1及AngⅡ含量较起搏前升高,有极显著性差异(P＜0.01).结论:血小板聚集功能增强、血浆vWF和ET-1含量升高,是导致心力衰竭血栓前状态形成的重要因素之一.     

快速右房起搏致猪心动过速性心肌病

目的通过快速右房起搏建立心动过速性心肌病模型,观察该病不同时期血流动力学改变和心肌重构情况。方法将15头滇南小耳猪,按随机区组的方法分为起搏1周组、起搏4周组、假手术组,分别采用240次/分快速起搏右房1周、4周和只手术不起搏。运用超声心动图和左心导管检查测量窦性心律下的血流动力学参数并观察心脏大体结构变化。经Masson染色检测心肌纤维化,测定心肌胶原容积分数(CVF),比较房、室重塑差异。结果起搏1周组左室射血分数、左室收缩末压、左室压力上升最大速率、左室压力下降高峰速率均较假手术组降低(P<0.01);起搏4周组上述血流动力学指标继续恶化,且腔室扩大、室壁变薄,(P<0.01)。心房、心室CVF随起搏时间的延长逐渐增加(P<0.01)。结论采用快速右房起搏成功制作了心动过速性心肌病模型,证实该病是以严重的左、右室舒缩功能障碍,腔室扩大,室壁变薄,心肌重塑为特征。     

高渗盐水对心力衰竭犬心脏功能和肾脏血流量的影响

目的探讨高渗盐水对心力衰竭犬心脏结构功能、血流动力学及肾脏血流量的作用。方法用快速心室起搏法建立心衰犬模型,分为假手术组、对照组、盐水组、速尿组、盐水+速尿组,分别在起搏前、起搏6周、盐水治疗2周后观测下列指标:超声心动检查,测量左室舒张末径（LVEDD）,左室收缩末径（LVESD）,左室射血分数（LVEF）、心排出量（CO）、肾脏血流量（RBF）;漂浮导管测量右房压（RAP）、平均肺动脉压（MPAP）、肺毛细血管楔嵌压（PCWP）、平均动脉压（MAP）、左室舒张末压（LVEDP）。结果单纯模型组与假手术组比较,血流动力学变化明显,RAP、PCWP、LVEDP升高,MAP降低,超声观测LVESD、LVEDD增大,LVEF、CO、RBF显著下降（P<0.05或P<0.01）;高渗盐水+速尿组,LVEF、CO、RBF、MAP明显增加,LVEDD、RAP、LVEDP、PCWP降低明显;高渗盐水组RBF较对照组有显著差异（P<0.05或P<0.01）;速尿组各指标与对照组比较均无变化。结论高渗盐水配合速尿能够增加心衰犬肾脏血流量,改善其降低的肾灌注,并改善部分心脏结构和功能指标和血流动力学状况。     

双腔起搏房室延迟时间对心功能的影响

目的观察不同房室延迟(AVD)的双腔起搏对心脏收缩、舒张功能的影响及不同心功能状态下的优化AVD。方法测量20例心力衰竭患者及10例心功能正常者(对照组)不同房室延迟起搏的急性血流动力学效应,同时以脉冲多普勒超声心动描记术测量心脏收缩、舒张功能指标。结果心力衰竭组房室延迟在134±13、131±12、136±10ms起搏时,血流动力学指标及左心室收缩功能、右心室舒张功能指标较AVD基线穴100ms雪及250ms显著改善;140±17ms起搏时,左心室舒张功能指标较AVD基线及250ms显著改善。对照组AVD在162±14ms起搏时,血流动力学参数较AVD基线及250ms显著改善。结论优化AVD可即刻改善心力衰竭患者心脏收缩及舒张功能,优化AVD随心功能状态不同而改变。     

多点组合同步心脏起搏对犬心肌力学和心脏作功的影响

多部位组合心脏起搏作为一种全新起搏模式 ,旨在通过实现心脏电 机械活动的再同步 ,提高心室舒张充盈和收缩射血功能 ,产生良好的血流动力学状态 ,达到近似生理性心脏起搏的目的。本文对比研究了右心室双部位起搏、双心室同步起搏和双心室三点同步起搏时对犬心肌力学和心脏作功的影响。资料和方法　实验动物与分组　健康犬 12只 ,雌雄各半 ,体重 (14 3± 2 3)ｋｇ。对每只动物采用自身对照的方法 ,按照不同起搏位点随机组合成以下各组起搏方式 (1)近希氏束 右心室尖双点起搏组 (ｃＨｉｓＢ ＲＶＡ起搏组 ) ;(2 )右心室尖 左心室后侧壁双心…     

右心室流入道间隔部起搏血流动力学研究

目的本文旨在对右心室流入道间隔部起搏的血流动力学进行分析,以确立右心室流入道间隔部起搏的临床地位。方法本研究通过射频消融房室结建立Ⅲ°房室传导阻滞模型,结合影像学及心电图定位方法于右心室流入道间隔部置入螺旋电极导线,并分别比较右心室心尖部、右心室流出道及右心室流入道间隔部起搏后急性血流动力学指标变化,并随访右心室流入道间隔部起搏2周后的血流动力学指标。结果即刻血流动力学研究结果显示,右心室流入道间隔部较心尖部和右心室流出道起搏心排血量高(P<0.05),左心室舒张末期压力较低(P<0.05),而右心室流入道间隔部起搏前后各项血流动力学无显著变化。结论右心室流入道间隔部起搏具有良好的血流动力学效应,可作为右心室心尖部起搏的替代起搏部位。     

频发房性期前收缩对犬心肌功能影响的研究

目的观察频发房性期前收缩对犬心功能的影响。方法 6只杂种犬植入双腔起搏器,两根电极均植入心室,3只犬为对照组,3只犬为起搏组,起搏组通过调节房室传导时间造成房性期前收缩两联律模型。起搏前和起搏4周后彩色超声心动图测量左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)。结果起搏组和对照组在4周前LVEDD、LVESD、LVEF比较均无统计学意义(P0.05)。在4周后LVEDD、LVESD比较未见明显的变化(P0.05),而起搏组LVEF较对照组有明显下降,差异有统计学意义(P0.05)。起搏组和对照组在4周前后各组内的LVEF、LVEDD、LVESD比较均无统计学意义(P0.05)。结论长时间高负荷的房性期前收缩对犬心脏LVEDD和LVESD无明显影响。但会造成LVEF的下降。     

快速右室起搏建立动物心力衰竭模型

为建立稳定的慢性终末期心力衰竭 (简称心衰 )动物模型 ,选择太湖梅山猪 12只 ,采用快速 (2 30次 /分 )右室起搏 4周 ,之后改用 190次 /分的频率维持右室起搏 4周。并应用超声心动图及心导管检查 ,观察猪在实验的不同阶段心功能参数。结果 :快速起搏 4周后 ,所有猪均出现明显的充血性心衰的表现 ;超声心动图显示心室壁变薄、射血分数、心输出量明显下降 ;心导管检查结果示肺动脉压、右房压、肺动脉楔压升高 ,而心输出量、每搏输出量和动脉压降低 ;在以 190次 /分维持 4周后 ,上述参数仍保持稳定。结论 :快速右室起搏可建立稳定、持久的慢性终末期心衰模型。     

Electrical Remodeling and Atrial Dilation During Atrial Tachycardia are Influenced by Ventricular Rate: Role of Developing Tachycardiomyopathy

INTRODUCTION: Atrial fibrillation (AF) and congestive heart failure (CHF) are two clinical entities that often coincide. Our aim was to establish the influence of concomitant high ventricular rate and consequent development of CHF on electrical remodeling and dilation during atrial tachycardia. METHODS AND RESULTS: A total of 14 goats was studied. Five goats were subjected to 3:1 AV pacing (A-paced group, atrial rate 240 beats/min, ventricular rate 80 beats/min). Nine goats were subjected to rapid 1:1 AV pacing (AV-paced group, atrial and ventricular rates 240 beats/min). During 4 weeks, right atrial (RA) and left ventricular (LV) diameters were measured during sinus rhythm. Atrial effective refractory periods (AERP) and inducibility of AF were assessed at three basic cycle lengths (BCL). After 4 weeks of rapid AV pacing, RA and LV diameters had increased to 151% and 113% of baseline, whereas after rapid atrial pacing alone, these parameters were unchanged. Right AERP (157+/-10 msec vs 144+/-16 msec at baseline with BCL of 400 msec in the A-paced and AV-paced group, respectively) initially decreased in both groups, reaching minimum values within 1 week. Subsequently, AERP partially recovered in AV-paced goats, whereas AERP remained short in A-paced goats (79+/-7 msec vs 102+/-12 msec after 4 weeks; P < 0.05). Left AERP demonstrated a similar time course. Inducibility of AF increased in both groups and reached a maximum during the first week in both groups, being 20% and 48% in the A-paced and AV-paced group, respectively. CONCLUSION: Nature and time course of atrial electrical remodeling and dilation during atrial tachycardia are influenced by concurrent high ventricular rate and consequent development of CHF.     

快速右室起搏致充血性心力衰竭犬心室复极离散性的变化

目的研究快速右室起搏致充血性心力衰竭(CHF)犬心室复极离散性的变化。方法25只犬随机分成两组:对照组(n=10)及CHF组(n=15)。应用快速右室起搏(240次/分,共4～5周)制作CHF犬模型,应用心脏电刺激技术测定心电生理参数。结果与对照组比较,CHF组左右室的心室兴奋恢复时间(VRT)均明显延长(P<0.01),心尖部的VRT延长更明显(P<0.05),VRT离散性(DVRT)明显增加(32±6msvs13±4ms,P<0.01);左室三层心肌VRT均明显延长(P<0.01),中层心肌的VRT延长更明显(P<0.05),跨室壁DVRT(TDVRT)明显增加(44±8msvs19±5ms,P<0.01);CHF组心室颤动阈值(VFT)明显降低(11±3mAvs34±7mA,P<0.01)。结论CHF犬DVRT及TDVRT明显增大,使心室复极不均一,易致折返活动,同时VFT降低。     

Atrial natriuretic peptides during experimental atrial tachycardia: role of developing tachycardiomyopathy

INTRODUCTION: Atrial tachycardia and chronic heart failure (CHF) are associated with elevated levels of atrial natriuretic peptide (ANP) and its amino terminal part NT-ANP. Chronic high atrial rates may cause CHF due to a rapid ventricular response. The aim of this study was to establish the contribution of elevated atrial rate and of high ventricular rate, resulting in CHF, on ANP and NT-ANP levels during chronic atrial tachycardia. METHODS AND RESULTS: Thirteen goats (AV-paced group) were subjected to 4 weeks of rapid AV pacing with an atrial and ventricular rate of 240 beats/min. Another five goats (A-paced group) were subjected to 4 weeks of atrial pacing at 240 beats/min while the ventricular rate was kept low and regular at 80 beats/min. Pacing was interrupted only for measurement of right atrial (RA) and left ventricular (LV) diameter and sampling for ANP, NT-ANP, and renin. In the AV-paced group, RA and LV diameter reached 152% and 109% of baseline values, respectively. Both ANP and NT-ANP (8.3 +/- 9.2 pmol/L and 0.5 +/- 0.4 nmol/L at baseline, respectively) increased progressively (53.1 +/- 37.9 pmol/L and 2.0 +/- 0.9 nmol/L, respectively, after 4 weeks). There was a significant correlation between the magnitude of atrial dilation and natriuretic peptide levels after 3 days. In A-paced goats, however, RA and LV diameters did not change. Furthermore, ANP and NT-ANP levels (9.1 +/- 6.0 pmol/L and 0.8 +/- 0.2 nmol/L at baseline, respectively) were unchanged after 4 weeks (5.3 +/- 3.4 pmol/L and 0.6 +/- 0.2 nmol/L, respectively). CONCLUSION: Elevated levels of ANPs during chronic atrial tachycardia are related to a high ventricular rate rather than a high atrial rate alone. Rather than atrial tachycardia, the atrial hemodynamic burden is an important determinant of the sustained ANP response.     

Atrial ultrastructural changes during experimental atrial tachycardia depend on high ventricular rate

INTRODUCTION: Atrial structural and electrophysiologic changes occur during atrial tachycardia. The role of high ventricular rate in these processes remains to be established. METHODS AND RESULTS: Six goats were subjected to 4 weeks of rapid atrioventricular (AV) pacing at an atrial and ventricular rate of 240 beats/min, resulting in development of congestive heart failure. In another five goats, AV block was created. These goats then were subjected to 4 weeks of atrial pacing, also at 240 beats/min while the ventricular rate was kept low and regular at 80 beats/min (A-paced). Pacing was interrupted only for measurement of atrial effective refractory period and right atrial diameter. The ultrastructure of both atria was examined by light and electron microscopy, including quantification of the percentage of atrial extracellular matrix (%ECM). A group of six goats served as controls. In the AV-paced group, severe structural remodeling occurred in the atria, including severe loss of sarcomeres, glycogen accumulation, disruption of sarcoplasmic reticulum, and appearance of numerous small mitochondria and nuclei with homogeneously distributed chromatin. In contrast, structural changes were virtually absent in the atria of A-paced goats. Only a redistribution of nuclear chromatin and the appearance of numerous mitochondria were observed. The ultrastructure was normal in control animals. The%ECM was increased in AV-paced goats (29%) compared to A-paced animals (18%) and controls (17%) (P < 0.05). Finally, right atrial diameter increased by 51% in AV-paced goats but was unchanged in A-paced goats (P < 0.05). In both experimental groups, atrial effective refractory period shortened during pacing. CONCLUSION: Structural remodeling during chronic atrial tachycardia is related to the concomitant presence of a high ventricular rate and hence the occurrence of congestive heart failure rather than a high atrial rate. Electrical remodeling can occur in the absence of significant structural changes.     

Effects of chronic, rapid right atrial pacing on cardiac hemodynamics and myofibrillar ATPase activity in piglets

OBJECTIVES: To determine whether chronic, rapid right atrial pacing in newborn neonatal piglets has any effects on cardiac hemodynamics, and whether these changes are associated with intrinsic alterations in cardiac contractile potential as shown by cardiac myofibrillar calcium ATPase activity. BACKGROUND: Although many studies have examined aspects of heart function in models of supraventricular tachycardia, far less is known about its effects in neonatal animals. It is thought that rapid pacing induces a dilated cardiomyopathy in immature pigs. ANIMALS AND METHODS: Two-week-old piglets underwent rapid right atrial pacing (250 beats/min) for 10 days, and their cardiac hemodynamic response was monitored. To obtain subcellular mechanistic information regarding systolic dysfunction, cardiac myofibrils were isolated and calcium adenosine triphosphatase activity was measured. RESULTS: Control piglets had a heart rate of 185 beats/min at the end of the experimental period. Pulmonary artery flow, pulmonary artery flow index and left ventricular end-diastolic diameter were unchanged as a function of rapid, chronic right atrial pacing. Aortic pressure decreased in the paced piglets. Left atrial pressure increased approximately threefold in the paced animals. Left ventricular end-systolic diameter was also significantly higher after pacing, but left ventricular end-diastolic diameter was unchanged. Left ventricular shortening fraction was depressed approximately 50%. Myofibrillar calcium adenosine triphosphatase activity was significantly depressed as a function of pacing. CONCLUSIONS: Neonatal piglets undergoing chronic supraventricular tachycardia exhibit systolic dysfunction in the absence of dilation. The depression in contractile protein calcium adenosine triphosphatase activity provides information at a subcellular level regarding the mechanism responsible for this cardiomyopathy.     

Characterization of sustained atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure

INTRODUCTION: Atrial arrhythmias often complicate congestive heart failure (CHF). We characterized inducible atrial tachyarrhythmias and electrophysiologic alterations in dogs with CHF and atrial enlargement produced by rapid ventricular pacing. METHODS AND RESULTS: Endocardial pacing leads were implanted in the right ventricle, right atrium, and coronary sinus in 18 dogs. The right ventricular lead was connected to an implanted pacemaker capable of rapid ventricular pacing. The atrial leads were used to perform electrophysiologic studies in conscious animals at baseline in all dogs, during CHF induced by rapid ventricular pacing at 235 beats/min in 15 dogs, and during recovery from CHF in 6 dogs. After 20 +/- 7 days of rapid ventricular pacing, inducibility of sustained atrial tachycardia (cycle length 120 +/- 12 msec) was enhanced in dogs with CHF. Atrial tachycardia required a critical decrease in atrial burst pacing cycle length (< or = 130 msec) for induction and often could be terminated by overdrive pacing. Calcium antagonists (verapamil, flunarizine, ryanodine) terminated atrial tachycardia and suppressed inducibility. Effective refractory periods at 400- and 300-msec cycle lengths in the right atrium and coronary sinus were prolonged in dogs with CHF. Atrial cells from dogs with CHF had prolonged action potential durations and reduced resting potentials and delayed afterdepolarizations (DADs). Mitochondria from atrial tissue from dogs with CHF were enlarged and had internal cristae disorganization. CONCLUSIONS: CHF promotes inducibility of sustained atrial tachycardia. Based on the mode of tachycardia induction, responses to pacing and calcium antagonists, and presence of DADs, atrial tachycardia in this CHF model has a mechanism most consistent with DAD-induced triggered activity resulting from intracellular calcium overload.     

双室同步起搏的临床应用及置入左室电极的初步体会

观察双室同步起搏治疗充血性心力衰竭 (CHF)的疗效 ,探讨左室电极置入的方法及注意事项。 10例患者均为原发性扩张型心肌病 (DCM)并CHF ,符合双室同步起搏治疗的指征。其中 8例置入Medtronic 2 187电极 ,1例置入Medtronic 2 188电极 ,1例置入右室主动固定电极。 9例左室电极置入成功 ,1例失败改行右室双部位起搏 ,术后患者左室舒张未径、左室射血分数及 6min步行距离均有改善 (术后 3个月与术前分别比较 :70 .8± 9.5vs 79.5± 12 .5mm ,0 .4 2± 0 .13vs 0 .2 5± 0 .10 ,384 .8± 4 5 .4vs 2 78.6± 34.5m ;P <0 .0 5或 0 .0 1)。借助电生理冠状静脉窦 (CS)标测电极、CS造影 (包括直接逆行CS造影和冠状动脉造影使CS间接显像 )对指导左室电极的置入有较大的价值。结论 :双室同步起搏治疗CHF疗效肯定 ,借助CS标测电极及CS造影可提高左室电极置入的成功率     

Direct Effects of chronic beta-adrenergic receptor blockade on left ventricular and myocyte function in a model of tachycardia-induced congestive heart failure

Background:

Chronic beta-receptor blockade (beta-blockade) has been reported to improvesymptoms and increase survival in patients with congestive heart failure (CHF); however, whether the mechanisms for the effects of beta-blockade in CHF are due to modulating chronotropy, inotropy, or both remains unknown. To address this issue, left ventricular function and isolated myocyte function were examined with chronic beta-blockade in a rapid pacing model of CHF, thereby eliminating potential chronotropic effects of beta-blockade.

Methods and Results:

Pigs were randomly assigned to three groups of six pigs each: supraventriculartachycardia (SVT): 3 weeks of atrial pacing at 240 beats/min; SVT/beta-blockade: 3 weeks of rapid pacing and beta-blockade (25 mg atenolol twice daily on days 14–21 of pacing); control group, sham control animals. This dosage schedule for beta-blockade was chosen because catecholamines are persistently elevated by day 14 in this model of CHF. Left ventricular fractional shortening and end-diastolic dimension were measured by echocardiography in the conscious state with a resting ambient heart rate. Isolated left ventricular myocyte function was examined using high-speed videomicroscopy. Supraventricular tachycardia caused left ventricular dilation (5.4 ± 0.1 vs 3.5 ± 0.1 cm) and reduced fractional shortening (12 ± 1% vs 35 ± 1%) compared with control animals (P < .05). The SVT/beta-blockade group showed no significant effects on left ventricular size or function compared with the SVT group, but their ambient resting heart rate was reduced by 20% relative to the SVT group (P < .05). Myocyte shortening was reduced in the SVT group (2.2 ± 0.1% vs 4.5 ± 0.1%, P < .05) compared with the control group and increased from SVT only values with beta-blockade (2.7 ± 0.1%, P < .05). Similarly, myocyte shortening velocity was similarly reduced in the SVT and SVT/beta-blockade groups (31 ± 1 and 32 ± 1 μm/s) compared with the control group (51 ± 1 μm/s, P < .05). With SVT/beta-blockade myocyte contraction duration was prolonged (525 ± 5 ms) compared with SVT-only or control values (469 ± 9 and 473 ± 4 ms, P < .05). Thus, institution of beta-1-selective blockade during the development of SVT-induced CHF altered the temporal characteristics of the myocyte contraction process, which resulted in improved myocyte shortening.

Conclusions:

In a model of CHF due to the maintenance of a chronically elevated heart rate,institution of beta- 1-selective blockade during the progression of the CHF process minimally affected left ventricular size and function. At the level of the myocyte, chronic beta- 1-recep for blockade prolonged the contraction interval and thereby increased myocyte shortening. These unique results suggest that a contributory mechanism for the effects of beta-blockade in the setting of CHF is chronotropic modulation.