蜂王浆对低钙条件下离体蟾蜍心脏心率和心肌收缩力的影响

目的 观察不同浓度蜂王浆溶液对离体蟾蜍心率和心肌收缩力的影响.方法 30只蟾蜍随机分为任氏液组、任氏液+蜂王浆组和低钙任氏液+蜂王浆组,每组10只.采用斯氏法制备离体蛙心灌流标本.对照组离体蟾蜍心脏只灌流任氏液,任氏液+蜂王浆组在离体蟾蜍心脏的灌流任氏液中加入蜂王浆溶液,低钙任氏液+蜂王浆组在离体蟾蜍心脏灌流低钙任氏液中加入蜂王浆溶液.通过蟾蜍心室外采用心室收缩波动、心室吸收药物的方法给药,心室外容积固定为1.0 ml,根据所需蜂王浆浓度计算出加入原浆蜂王浆的容积,每次加入蜂王浆后记录10～20 min.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,并进行心肌收缩力和心率的统计学分析.结果 任氏液+蜂王浆组与任氏液组比较,在1:5 000浓度时蜂王浆能明显抑制离体蟾蜍心脏的心率和心肌收缩力(P＜0.05);在1:500浓度时,蜂王浆可显著抑制离体蟾蜍心脏的心率和心肌收缩力,甚至心脏停止跳动呈剂量依赖关系;低钙任氏液+蜂王浆组与任氏液组比较,在1:10 000浓度时蜂王浆明显抑制离体蟾蜍心脏的心率和心肌收缩力(P＜0.05);在1:1 000浓度时,蜂王浆显著抑制离体蟾蜍心脏的心率和心肌收缩力,甚至心脏停止跳动呈剂量依赖关系.低钙任氏液+蜂王浆组与任氏液+蜂王浆组比较,在1:5 000浓度蜂王浆能明显抑制离体蟾蜍心脏的心率和心肌收缩力(P＜0.05).结论 在低钙条件下,蜂王浆对离体蟾蜍心脏活动的抑制比在正常钙任氏液条件下更容易出现.     

缝隙连接阻滞剂Heptanol对心脏血流动力学的影响

目的:观察缝隙连接阻滞剂Heptanol对离体SD大鼠心脏机械功能及缺血心肌组织的影响。方法:(1)建立离体SD大鼠心脏Langendorff灌流模型,灌流含有Heptanol的K-H灌流液,观察离体SD大鼠心脏收缩及舒张功能。(2)结扎左前降支,建立局部心肌缺血模型,观察Heptanol对缺血心脏的机械功能的作用。(3)透射电镜观察Heptanol对缺血心肌结构的影响。结果:(1)Heptanol可以降低正常心脏的左室压力最大上升速率(dp/dt max)和左室收缩峰值(LVSP),对左室舒张末压(LVEDP)没有明显影响。(2)缺血心脏的LVSP、dp/dt max下降,LVEDP上升。Heptanol对缺血心脏的LVSP、dp/dtmax、LVEDP均无明显影响。(3)透射电镜观察可见缺血使心肌组织遭到破坏,Heptanol可以减轻组织损伤。结论:(1)Heptanol可以使正常心脏的收缩功能下降,对舒张功能无明显影响,不会使缺血心脏的机械功能进一步下降。(2)Heptanol可以减轻由于缺血造成的心肌组织破坏。     

肿瘤坏死因子α对离体大鼠心脏收缩性的影响

目的 :探讨肿瘤坏死因子 α(TNF α)对离体大鼠心脏收缩功能的影响。方法 :采用大鼠离体等容心脏灌流模型观察TNF α对心脏收缩功能指标的影响〔包括左室收缩压 (LVSP)和左心室内压力最大上升速率 (+dp/dtmax)〕。结果 :TNF α灌流心脏 15min和 2 0min时 ,可见LVSP和 +dp/dtmax明显降低 (P <0 .0 5 ) ,继续灌流 30min后 ,上述指标基本恢复 (P >0 .0 5 )。 结论 :一定浓度的TNF α对离体心脏具有可逆性负性肌力效应。     

牵张激活通道对膨胀心室大鼠原癌基因c-fos表达的影响

目的:研究牵张心室时牵张激活通道（SACs）对心肌细胞表达原癌基因c-fos的影响。方法:离体灌流大鼠心脏并膨胀左心室30 m in,停止灌流剪下左心室,抽提组织总RNA行半定量RT-PCR,探讨牵张左室对心室细胞表达c-fos的影响及SACs在其中的可能作用。结果:RT-PCR结果示,在同样牵张力度及持续时间膨胀心室的条件下,牵张加链霉素组c-fos表达水平明显低于无链霉素组。结论:SACs通道阻断剂-链霉素对膨胀左室致c-fos表达有明显抑制作用,间接说明心室膨胀经SACs激活胞内信号诱导c-fos表达;同时链霉素并不能完全抑制c-fos表达,提示膨胀心室致c-fos表达进而引起心室肥厚尚有其他传导途径,仍需进一步研究。     

镁对离体大鼠正常和缺血心脏室颤阈值的影响

本文观察Mg~(2 )对正常和局部缺血离体大鼠心脏VFT的影响。结果表明:提高灌流液Mg~(2 )浓度(正常值2倍)时,可使正常或局部缺血大鼠心脏的VFT增高;提高灌流液Ca~(2 )(正常值2倍)时,VFT下降,若再提高Mg~(2 )浓度,可使已下降的VFT增高;高Mg~(2 )使正常和高Ca(2 )时心室的收缩强度减弱。提示高Mg(2 )降低心室易颤性的机理可能是通过竞争拮抗减少Ca~(2 )内流,降低细胞内Ca~(2 )含量有关。     

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。     

线粒体膜钾通道阻断剂在硫化氢对大鼠心功能调节的意义

目的 观察线粒体膜KATP通道特异性阻断剂5-羟基葵酸盐(5-hydroxydecanoate,5-HD)对硫化氢(H2S)灌流的大鼠离体心脏心功能的影响,以探讨线粒体膜KATP通道阻断剂在H2S调节心功能过程中的意义.方法 应用Langendorff灌流大鼠离体心脏,用生理浓度NaHS(100 μmol/L)持续灌流20 min,测最心率、左室内压差(△LVP=左室收缩压-左室舒张压)、左室内压变化速率(±dp、dtmax)、冠状动脉流量等指标,分别应用非特异性KATP通道阻断剂格列苯脲、线粒体膜KATP通道阻断剂5-HD预灌流,后给予生理剂量NaHS灌流,观察其是否可以阻断H2S的心功能效应.结果 生理剂量NaHS持续灌流20 min内,可以显著抑制±dp/dtmax及ALVP(P<0.05),而对心率、冠状动脉流量几乎没有影响.非特异性KATP通道阻断剂格列苯脲及线粒体膜KATP通道阻断剂5-HD均可以大部分阻断生理剂量NaHS对心功能的抑制效应.结论 内源性H2S可以通过开放线粒体膜KATP通道,产生对心肌的负性肌力调节作用.     

丙泊酚对心肌肥厚大鼠离体心脏功能的保护作用

目的观察丙泊酚(propofol)对心肌肥厚大鼠离体心脏功能的影响,并探讨其作用机制。方法采用Langendorff心脏灌流实验方法,观察Propofol对心肌肥厚大鼠离体心脏功能的影响。观察不同阻断剂对Propofol作用的影响。结果 Propofol可增强心肌肥厚大鼠离体心脏心功能,心率减慢,主动脉收缩压(LVSP-LVDP)升高,左室压最大上升速率(+dp/dt_(max))升高,左室压最大下降速率(-dp/dt_(max))降低,吲哚美辛预处理后,Propofol对心脏功能的影响减弱。结论 Propofol可以明显改善心肌肥厚大鼠离体心脏功能,其作用可能与前列环素(PGI_2)的合成有关。     

改良成年小鼠心室肌细胞分离方法

目的 小鼠是优良的背景基因动物,分离成体原代心肌细胞可以真实地从细胞和分子水平反映单个心室肌细胞的功能。小鼠心室肌细胞的分离和大鼠相比较困难,分离获得的细胞存活率较低,为提高小鼠心室肌细胞的成活率和收获量,本研究团队通过艰苦的摸索,改进了小鼠成体心肌细胞的分离方法。方法 该方法采用心脏在体主动脉插管,行独创的前加压灌流法冲洗心脏后接入改进的langendorff装置,用胶原酶液II灌流、消化心脏后,将心脏剪碎并用吸管吹打,经200目滤网过滤后获得单个小鼠心室肌细胞。本研究检测并对比了在体和离体主动脉插管获得的心肌细胞的状态：梯度复钙后,在倒置显微镜下观察细胞的形态和杆状心室肌细胞的数目。结果 研究结果显示：改良的主动脉逆行灌流法在缩短手术时间的同时,提高了小鼠心室肌细胞收获量和存活率。本课题组利用医用三通管,独创倒置灌流排气法,可以迅速排空灌流装置中的气体;利用注射器和灌流针结合,独创前加压灌流法,可以快速彻底地冲洗心脏中的血液;并采用实验室常规眼科镊和血管钳巧妙组合成协助装置,可以单人独立完成插管,不需要助手协助,节约人力,节省经费开支。结论 这一方法的改进使整个实验流程简化,缩短了实验时间,操作简便易学;同时该分离方法稳定、可靠、有效,可以为同类型实验提供思路和借鉴。     

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。     

Postconditioning with glucagon like peptide-2 reduces ischemia/reperfusion injury in isolated rat hearts: role of survival kinases and mitochondrial KATP channels

We recently reported that heart expresses functional receptors for the anorexigenic glucagon-like peptide (GLP)-2. Activation of these cardiac receptors affected basal heart performance through extracellular regulated kinase (ERK1/2) activation. Since ERK1/2 is considered one of the prosurvival kinases of postconditioning cardioprotective pathways, we hypothesized that GLP-2 directly protects the heart against ischemia/reperfusion (I/R) injury via prosurvival kinases. Wistar rat hearts were retrogradely perfused on a Langendorff perfusion apparatus. After 40-min stabilization, hearts underwent 30-min global ischemia and 120-min reperfusion (I/R group). In GLP-2 group, the hearts received 20-min GLP-2 (10(-7)?M) infusion at the beginning of the 120-min reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated by nitroblue-tetrazolium staining. Compared with the I/R group, GLP-2-treated hearts showed a significant reduction of infarct size and of postischemic diastolic LVP (index of contracture), together with a sharp improvement of developed LVP recovery (index of contractility). The protective effects were abolished by co-infusion with phosphatidylinositol 3-kinase inhibitor, Wortmannin (WT), the ERK1/2 inhibitor, PD98059, or the mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate. GLP-2 effects were accompanied by increased phosphorylation of protein kinase B (PKB/Akt), ERK1/2 and glycogen synthase kinase (GSK3β). After 7-min reperfusion, WT blocked Akt and GSK3β phosphorylation. After 30-min reperfusion, WT inhibited phosphorylation of all kinases. In conclusion, the data suggest that GLP-2, given in early reperfusion, as postconditioning, protects against myocardial I/R injury, limiting infarct size, and improving post-ischemic mechanical recovery. It seems that the GLP-2-protection of rat heart involves multiple prosurvival kinases and mitochondrial K(ATP) channels.     

Effects of norepinephrine on hypoperfusion-reperfusion injuries in hearts isolated from normal and diabetic rats

Contractile and energy-metabolic functions were investigated in paced hearts isolated from normal (Normal) and streptozotocin-diabetic rats (DM) during hypoperfusion at 1 ml/min with or without 10(-6) M norepinephrine (NE) and during reperfusion at the pre-hypoperfusion flow. Left ventricular pressure (LVP) and contractile force (CF) were monitored, respectively, through a water-filled balloon in LV and through a hook attached to the apex. A 1-h hypoperfusion without NE caused significant elevations in resting LVP and resting CF only in DM hearts, smaller transmural lactate accumulations in DM hearts, and similar ATP decreases in both groups. Significant decreases in developed LVP and developed CF were observed in both groups. NE during hypoperfusion caused deterioration of these cardiac dysfunctions in both groups, particularly in DM hearts. A 1-h reperfusion caused elevations in resting LVP and resting CF with no recovery in developed CF in Normal hearts, while it caused partial recovery in resting and developed CF in DM hearts. Both groups showed similar partial recovery of ATP. NE during hypoperfusion improved the mechanical dysfunction during reperfusion in DM hearts, but there was a smaller recovery in ATP than in hearts without NE. In vivo insulin treatment in DM restored the cardiac functions to Normal levels. Thus, DM hearts were more vulnerable to hypoperfusion, while Normal hearts were more vulnerable to reperfusion injury.     

Correlation of contractile dysfunction and abnormal tissue energy metabolism during hypoperfusion with norepinephrine in isolated rat hearts: differences between normal and diabetic hearts.

The relationship of myocardial high-energy phosphate depletion and lactate accumulation with contractile dysfunctions was investigated in streptozotocin-diabetic (DM) and normal rat hearts. The isolated hearts were perfused with 10(-6) M norepinephrine (NE) at various low-flow rates (0.4-6 ml/min/g heart wt) for 1 h. Left ventricular pressure (LVP) and contractile force (CF) were monitored, through a water-filled balloon in LV and through a hook attached to the apex, respectively. In DM hearts resting CF (diastolic tension) increased, when the perfusion flow rate was reduced below 6 ml and reached a maximum at a flow rate of less than 3 ml. The large increase in LV stiffness correlated with an elevation in diastolic LVP. In normal hearts these parameters were elevated at a flow rate below 1 ml. A flow-dependent decrease in developed CF was more prominent in DM than in normal hearts, while developed LVP and perfusion pressure were slightly higher in DM hearts with a marked increase in the LV stiffness. A flow-dependent decrease in high-energy phosphates and increases in inorganic phosphate and lactate were more prominent in the inner than in the outer layer of LV free wall in both groups. The change of ATP in the inner layer was greater, while increases of lactate in both layers were smaller in DM hearts. Changes in mechanical parameters correlated well with the ATP decrease and lactate increase in the inner layer in both groups. The correlation curves, however, were not coincidental: at the same low ATP and high lactate level, the LV stiffness was higher in DM hearts. Results indicate that DM hearts are more susceptible to flow-reduction with NE and depletion of total ATP in their tissue, and easily suffer from increased LV stiffness. This cannot be explained by the rate of decrease in total ATP and lactate accumulation alone.     

Effects of neonatal hypoxia in the rat on inotropic stimulation of the adult heart

OBJECTIVE: To determine whether transient hypoxia in neonatal rats has long-lasting effects on inotropic stimulation of the adult heart. METHODS: The hearts of adult male Sprague-Dawley rats (89+/-1 (S.E.M.) days, 432+/-5 g) were studied. Half the animals had been subjected to neonatal hypoxia (FiO(2)=0.12, days 1-10) while the others had not. The peak response of left ventricular pressure (LVP) and the maximum rate of pressure increase (+dP/dtmax) were measured in isolated and perfused hearts during application of dobutamine, isoproterenol, milrinone and betaxolol. Left ventricular myocyte membranes were analyzed for beta receptor density, adenylyl cyclase activity and content. RESULTS: LVP and +dP/dtmax responses to stimulation with dobutamine and isoproterenol were significantly impaired in adult hearts of neonatally hypoxic rats. The inotropic effect of dobutamine was abolished by blockade with the beta(1)-selective antagonist betaxolol. The inotropic effects of the phosphodiesterase inhibitor milrinone were also significantly decreased in neonatally hypoxic adult hearts. There was no difference in left ventricular myocyte membrane beta receptor density of adult hearts whether they were hypoxic neonatally or not. However, left ventricular adenylyl cyclase activity on isoproterenol or forskolin stimulation and adenylyl cyclase levels (type V/VI) were significantly reduced in neonatally hypoxic adult hearts. CONCLUSIONS: Neonatal hypoxia in the rat has long-lasting effects on the left ventricular response to inotropic stimulation at maturity likely at least in part due to diminished left ventricular adenylyl cyclase levels.     

Noise levels of closing sounds in vivo are equal for different bileaflet mechanical heart valves

BACKGROUND AND AIM OF THE STUDY: Patients with mechanical heart valves must endure the valve's closing sounds for the rest of their life. Sound pressure levels (SPLs) recorded show wide patient-to-patient variation, even for the same type of valve. The variation was attributed to body constitution variability and differences in hemodynamic status. It was hypothesized that aortic mechanical valves generate closing clicks which correlate in magnitude with hemodynamic parameters, such as the rate of relaxation of the left ventricle (dp/dt) and potential energy stored in the aortic windkessel. METHODS: Three different aortic mechanical heart valves were investigated in a porcine model (n = 9), namely St. Jude Medical, CarboMedics and ATS. Closing sounds were measured with a microphone placed in a portable anechoic chamber 10 cm above the exposed heart. Left ventricular pressure (LVP) and cardiac output were also measured. Different hemodynamic conditions were produced by intravenous infusion of isotonic saline and dobutamine. Volume regulation and atrial pacing were also applied. RESULTS: Different hemodynamic situations were established (cardiac output, 1.2-6.5 l/min; heart rate, 99-171 bpm). The measured mean SPLs were 49.5-53.9 dB(A), and there were no statistically significant differences in noise between the valves (p = 0.8; one-way ANOVA). Likewise, only a weak relationship was identified between different hemodynamic parameters and the SPLs recorded. CONCLUSION: The SPLs of the investigated bileaflet mechanical heart valves did not differ significantly. Moreover, the SPL was only weakly related to LVP during closure and estimated stroke work.     

Effect of anesthesia on cardiac function and response in the perfused rat heart

In the present study we have examined the effect of the general anesthetic agent sodium pentobarbital (given i.p. to the intact animal) on the hemodynamic function of the isolated perfused heart and its response to treatments which affect calcium transsarcolemmal influx: extracellular calcium concentration and thyroid hormone. Perfused hearts (modified Langendorff system) isolated from anesthetized rats were found to respond differently to the two aforementioned effectors than hearts excised from non-anesthetized animals. Hearts of the two groups demonstrated a gradual increase in inotropic activity in response to step-wise increase in calcium concentration in the perfusion medium. However, cardiac contractility and the pattern of the response to the gradual increase in calcium concentration were different. At the lower Ca2+ concentrations of 0.5 and 1.0 mM, inotropic activity (left ventricular systolic pressure (LVP) and +dP/dt values) of hearts from anesthetized animals was significantly greater (P less than 0.05) than that of hearts from non-anesthetized animals: LVP values (mmHg, mean +/- S.E.M.) in hearts from anesthetized an non-anesthetized rats were: at 0.5 mM Ca2+, 19 +/- 3 and 9 +/- 2; and at 1.0 mM, 103 +/- 12 and 76 +/- 6, respectively. At the higher Ca2+ concentrations, hearts from anesthetized animals demonstrated maximal LVP at 1.75 mM calcium (139 +/- 9 mmHg), whereas the LVP values in hearts from non-anesthetized animals continued to increase throughout all the Ca2+ concentrations employed. A similar pattern of response was observed for +dP/dt values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible contribution of the sarcoplasmic reticulum Ca(2+) pump function to electrical and mechanical alternans

We investigated the role of the sarcoplasmic reticulum's (SR) Ca(2+) pump function of the in the mechanism of alternans. We recorded the surface ECG, monophasic action potential (MAP) and left ventricular pressure (LVP) in the canine beating heart. Alternans was induced with an abrupt shortening of the cycle length from 1000 to 350 ms. After the control studies, we administered propranolol or isoproterenol. In the presence of propranolol, we administered milrinone or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In the presence of isoproterenol, we administered thapsigargin. Isoproterenol and milrinone attenuated both the electrical and mechanical alternans. Thapsigargin, a specific SR Ca(2+) pump inhibitor, and propranolol magnified both types of alternans. DIDS, a Ca(2+)-activated Cl(-) current (I(Cl(Ca))) inhibitor, attenuated the MAP alternans without an affect on the LVP alternans. Thus, the delayed intracellular Ca(2+) cycling caused by the impaired SR Ca(2+) pump function might produce electrical and mechanical alternans. beta-adrenergic stimulation eliminated these alternans. The I(Cl(Ca)) contributed to the appearance of the electrical alternans.     

Acute hemodynamic effects of biventricular and left ventricular pacing in chronic pacemaker-dependent patients with advanced heart failure

The beneficial hemodynamic effects of cardiac resynchronization in patients with intraventricular conduction delay have been demonstrated. The potential hemodynamic effects of cardiac resynchronization to compensate the pacing-induced left ventricular conduction delay in chronically paced heart failure patients are not as well established. The aim of the study was to evaluate the acute hemodynamic effects of biventricular and left ventricular pacing in chronically paced patients with advanced heart failure.Fourteen consecutive pacemaker or defibrillator patients with permanent atrial fibrillation and AV block (11 male, 3 woman, mean age: 68 +/- 7 years) were enrolled in this study. There were 5 ischemic (36%) and 9 nonischemic (64%) patients (mean left ventricular ejection fraction: 19 +/- 5%; mean end-diastolic left ventricular diameter: 71 +/- 11 mm). In all patients a right ventricular and left ventricular (via coronary sinus) pacing lead was placed. The aortic and left ventricular hemodynamic measurements were performed using a two-channel micro-tip catheter. The measurements of the aortic pulse pressure (APP) and (dP/ dtmax) were performed during right ventricular apical pacing (RVP), left ventricular (LVP), and biventricular pacing (BVP) (70 bpm).Compared to RVP, LVP and BVP increased APP and dP/dtmax (35.8 +/- 4.2 vs 43.3 +/- 4.5 and 41.2 +/- 4 mmHg; p < 0.001) and (758 +/- 56 vs 967 +/- 60 and 961 +/- 62 mmHg/s; p < 0.001). LVP and BVP showed a comparable hemodynamic response. The hemodynamic effects were not related to the width of the paced QRS complex. Every patient showed improved hemodynamics during LVP and BVP unrelated to the underlying heart disease and to the baseline level of left ventricular dysfunction. BVP and LVP pacing acutely improve contractile left ventricular function in chronically paced patients with advanced heart failure.     

Comparison of Permanent Left Ventricular and Biventricular Pacing in Patients with Heart Failure and Chronic Atrial Fibrillation: A Prospective Hemodynamic Study

BACKGROUND: Left ventricular pacing (LVP) and biventricular pacing (BVP) have been proposed as treatments for patients with advanced heart failure complicated by discoordinate contraction due to intraventricular conduction delay. For patients in sinus rhythm, BVP works in part by modulating the electronic atrial-ventricular time delay and thus optimizing contractile synchrony, the contribution of atrial systole, and reducing mitral regurgitation. However, little is known of the mechanisms of BVP in heart failure patients with drug-resistant chronic atrial fibrillation. HYPOTHESIS AND METHODS: LVP differs from BVP because hemodynamic and clinical improvement occurs in association with prolongation rather than shortening of the QRS duration. We sought to determine if LVP or BVP improves mechanical synchronization in the presence of atrial fibrillation. Thirteen patients with chronic atrial fibrillation, severe heart failure and QRS >or=140 ms received (after His bundle ablation) a pacemaker providing both LVP and BVP. The mean age was 62 +/- 6 years and left ventricular ejection fraction was 24 +/- 8%. After a baseline phase of one month with right ventricular pacing, all patients underwent in random order 2 phases of 2 months (LVP and BVP). At the end of each phase, an echocardiogram, a hemodynamic analysis at rest and during a 6-minute walking test and a cardio-pulmonary exercise test were performed. RESULTS: LVP and BVP provided similar performances at rest (p = ns). The 6-minute walking test revealed similar performances in both pacing modes but patients were significantly more symptomatic at the end of the test with LVP ( p = 0.035). The cardio-pulmonary exercise test showed higher performances with BVP (92 +/- 34 Watts) vs. LVP (77 +/- 23; p = 0.03). LVP was associated with significantly more premature ventricular complexes recorded during the 6 minute walking test (49 +/- 71) than BVP (10 +/- 23; p = 0.04). CONCLUSIONS: In this small series of patients with atrial fibrillation, congestive heart failure and a prolonged QRS duration, LVP and BVP provided similar hemodynamic effects at rest whereas BVP was associated with better hemodynamic effects during exercise and fewer premature ventricular complexes. Although the mechanisms for the observed differences are uncertain, it is possible that there is worsening of right ventricular function due to a rise in left-to-right electromechanical delay during exercise. Increased catecholamines release might contribute to the lower exercise tolerance and greater number of premature ventricular complexes recorded during exercise observed during LVP compared to BVP. RECOMMENDATIONS: Patients with atrial fibrillation, heart failure and QRS prolongation who are candidates for His-bundle ablation and cardiac resynchronization therapy may respond better to BVP rather than to LVP.