急性低氧时狗左、右心室“力效应”的比较观察

在麻醉开胸狗上,于急性逐步加重低氧条件下,同步记录左、右心室压、压力变化率(dp/dt)等指标,观察左、右心室“力效应”动态变化过程。结果表明,急性低氧时,肺动脉升压效应与低氧程度呈正相关;左、右心室“力效应”并非同步。当左室“力效应”由增强转为减弱时,右室仍处于“力效应”增强过程,而且左室(-dp/dt_max)的减小先于(dp/dt_max)。严重低氧一旦使右室出现“力效应”减弱时,则标志着心泵功能崩溃。这些结果提示左室泵丧失代偿并非继发于肺动脉高压导致的右室负荷过重;心室舒张期力学的改变在心泵对急性低氧的反应上甚为重要,可用左心室进行性的“力效应”减弱作为判断心泵对急性低氧不能耐受的一项指标。     

阶梯式进行性急性低氧时Starling效应对左心室搏血效率的影响

为探讨急性低氧时 Starling 效应对左室搏血效率的影响,在12条麻醉开胸狗上进行了实验。给狗依次吸入氧分压为84、64、52mmHg 的氧氮混合气体和纯氮气造成急性低氧。我们将心泵急性低氧反应分为稳态调节、剧烈动员和衰竭三个阶段。在Starling 效应开始持续发动以前,心泵处于稳态调节阶段、左室舒张期末直径(LVEDD)、在室压力(LVP)、每搏输出量(SV)、每搏外功(W)、与每搏外功功率峰值(N_(max))等稳定于对照水平,略有波动。搏血效率指数(I_(BEE)=SV/N_(max))也稳定于对照水平。稳态调节阶段持续时间的长短与心泵能耐受低氧的程度和时间呈正相关(r=0.83,P<0.001)。在剧烈动员阶段,左室舒张期末直径进行性地迅速增大,从对照时的 51.55±1.09mm(M±SE)增至54.60±1.63mm(P<0.01)。同时,LVP、SV、W、N_(max)等泵功能指标也明显上升,形成一个显著高于对照值的峰(各指标与对照相比,均P<0.01)。此时,搏血效率指数仍维持于对照水平(P>0.05)。此结果表明;剧烈动员阶段时 Starlins效应的发动和维持,并未降低搏血效率,有利于心泵功能代偿。     

急性低氧时狗心泵代偿-失代偿转变的力学特征

为了分析急性低氧时心泵代偿-失代偿转变过程的力学特征,在22条麻醉开胸狗上,于吸入气氧分压递降条件下,作了心泵舒缩功能测定。结果表明,虽然严重低氧时心泵外功功率尚可保持在增大状态,但其压力作功成分减小,容积作功成分增大。动脉导纳的增加是容积作功增大的主要原因。这时,主动脉内有效血液推动力进一步增大,而泵缩力量却开始减弱。肌力效应在泵失代偿发生前,对舒缩功能的增强起着重要作用。在泵代偿-失代偿转变阶段,斯塔林效应的作用显著。“舒-缩谐调”的变化,早在泵失代偿前就已出现,并渐明显,值得注意。     

急性低氧时的Starling效应及心包的影响

为确定 Starling效应在心泵急性低氧反应中的地位,以及心包对此反应的影响,把17条雄狗,分别在心包切开(A 组)和缝合(B 组)条件下进行实验。在连续、依次吸入空气、氧分压为89、70和55mmHg 的常压氧-氮混合气各30min,并最后吸入氮气时,分别记录不同低氧状况下的左室前后径超声图、左室压力,dp/dt,右室压力或主动脉压力和第二导联心电图。结果表明,重度低氧时,左室舒张期末直径显著增大,A组由对照值3.88±0.15cm(M±SE)增大至4.22±0.18cm(P<0.01);B组由3.53±0.13cm增至3.67±0.12cm(P<0.01),并伴以每搏直径变化的明显增大(A 组由对照值的4.4±0.2mm增至4.9±0.2mm P<0.05;B 组由3.2±0.1mm 增至3.8±0.2mm P<0.01)。左室压力-直径环在重度低氧时显著右移,环体面积不缩小。说明重度低氧时,Starling 效应对心脏搏血功能的调节具有重要作用。在严重低氧导致左室收缩压进行性降低时,迅速切开心包可有利于心泵功能的改善,提示,心包对 Starling 效应的充分发挥有限制作用。     

急性低氧下钙阻断剂对左,右心泵功能的影响

在20条麻醉开胸狗上,用RM-6000多道仪同步记录左心室内峰压(LVP)、左室压力变化率(L+dP/dt_(max))、右心室内峰压(RVP)、右室压力变化率(R±dp/dt_(max))、肺动脉压力(P_(Pa))、主动脉血流每搏峰值(Fa)、心率(HR)等各项生理指标,观察钙通道阻断剂Nife-dipine,Diltiazem和Verapamil对左、右心室功能影响。在钙通道阻断剂处理后,左室的LVP,L±dp/dt_(max)下降,而Fa增加;右室的RVF,R±dp/dt_(max)和P_(Pa)均有升高趋势,显示钙通道阻断剂对左、右心泵功能的影响不同。这可能提示左、右心室功能对钙离子的依赖程度不同。在急性低氧状态下,此三种钙阻断剂均使急性低氧引起LVP的增加反应消失,Fa增加明显,Verapamil和Diltiazem有减轻急性低氧引起的RVP和P_(Pa)的增压作用。从这些钙通道阻断剂对左右心泵功能影响的比较来看,Diltiazem比Verapamil和Nifedipine对急性低氧状态下的心泵功能有较好的作用。     

清醒狗对急性低氧的心泵反应

6条清醒雄狗,于左心室和肺动脉干装置慢性导管,记录压力、dp/dt、d~2p/dt~2以及dp/dt/p 等。于手术后第4至第12天,给予轻度(p_(IO_2)=84mmHg)和中度(p_(IO_2)=64mmHg)低氧气体吸入,观察心泵反应。在24次实验中,都见到常用的泵功能指标增强,反应状况与麻醉开胸狗上的结果大体相似。但心率加速反应比麻醉犬明显。中度低氧时,dp/dt_max、左室与肺动脉压力常有强弱交替的周期性波动,此现象可被麻醉或β-及 α-受体同时阻断所消除。有时,当 dp/dt_max 值处于增大状态,dp/dt/p DP40值却减小。收缩相与舒张相d~2p/dt~2max 的比值(C/R),在中度低氧时增大(P<0.02),反映了收缩作用与舒张作用的反应不匹配,这可能是泵功能欠佳的早期信号。     

心脏急性低氧耐受性的研究——Ⅰ.急性低氧时狗心舒缩的力学分析

心脏作为搏送血液的泵(简称为心泵)的性能优劣,是决定人体在急性低氧应激中适应是否良好的一个重要环节。我们以前曾观察到,心泵性能优良的健康人能较好地耐受相当于海拔7500米的急性减压低氧,在攀登珠穆朗玛峰时,凡登达8200米以上的登山队员,其心泵性能显著优于只能登到6500米以下的队员。为了进一步探讨急性     

急性低氧对高原土生动物藏系绵羊血气的影响

为了探讨急性低氧时藏系绵羊(Ovis aries)的血气特点,揭示其低氧适应机制,将7只雄性藏系绵羊和5只雄性移居绵羊分别置于高低压氧舱内,测定模拟海拔0、2 300和4 500 m时各动物清醒状态下的血气指标。用热稀释法测定心输出量。使用血气分析仪和EG7血样板,测定动脉及混合静脉血的血气指标,按Ficks方法计算氧耗量。结果显示,随着模拟海拔高度的升高,藏羊和移居羊的动静脉血氧饱和度(So2)、氧分压(Po2)、二氧化碳分压(Pco2)都呈明显下降趋势(P<0.05),血红蛋白浓度(Hb)、血液pH、心输出量及氧耗量虽无明显的差异性改变,但它们在4 500 m处的绝对值是增加的。在相同海拔,藏羊的Hb明显低于移居羊(P<0.05),4 500 m时藏羊的动脉血氧饱和度(Sao2)及组织摄氧量显著高于移居羊(P<0.05)。表明藏羊在急性低氧时表现出的高Sao2及高组织摄氧量,低Hb、低pH是它适应高原低氧的生理基础。     

低氧增强清醒自发性高血压大鼠心血管-呼吸活动（英文）

激活外周化学感受器可以同时引起呼吸和心血管反射,此机制可能参与高血压形成过程中的交感神经过度激活。因此我们推测激活外周呼吸化学感受器可以显著增强高血压大鼠的心肺活动。本研究通过联合应用全身无创全体积描记术和无线生物信号遥测技术,观察急性低氧刺激对清醒自发性高血压大鼠(spontaneously hypertensive rat, SHR)和血压正常的对照Wistar-Kyoto (WKY)大鼠的肺通气、动脉血压和心率的影响。结果表明,急性低氧刺激引起SHR潮气量和每分通气量明显高于WKY大鼠,并且急性低氧引起SHR血压和心率的增加幅度更明显。切断支配大鼠颈动脉体的双侧窦神经后,SHR和WKY大鼠急性低氧通气反应均降低,并且两组间比较没有显著性差异。同时,在切断双侧窦神经后,急性低氧引起的两组动物的血压和心率变化均无显著性差异。本研究表明,急性低氧刺激显著增强SHR的心血管和呼吸效应,这可能与其颈动脉体外周呼吸化学感受器对低氧的敏感性增高有关。     

急性低氧对家兔血压心率微血管反应性及自由基的影响

目的 :探讨不同急性低氧下的血压、心率、微血管反应性和自由基的影响。方法 :实验采用家兔人工吸入含氧量为 12 .5 %和 8.5 %氮氧混合气体 (模拟 4 0 0 0m和 6 5 0 0m高原急性低氧 )。急性低氧时间分别为 5、10、15、2 0min ,观察血压、心率、微血管反应性和自由基影响。结果 :①急性低氧 5min时收缩压略有升高 ,以后变为降低 ;舒张压在急性低氧 2 0min后明显降低 (P <0 .0 5 ) ;②心率随急性低氧时间的延长变慢 ,尤其含氧量 8.5 %急性低氧组明显 (P <0 .0 5 )。③眼结膜微血管管径随急性低氧时间延长呈现扩张 (P <0 .0 5 ) ,血细胞流速减慢 (P <0 .0 5 ,P <0 .0 1)。④急性低氧 2 0min后SOD活力明显降低 (P <0 .0 5 ) ,MDA含量升高 (P <0 .0 5 )。结论 :急性低氧可使血压降低 ,心率减慢 ,微血管管径变大和血细胞流速减慢 ,同时体内自由基产生增加。     

Regulation of cardiomyocyte proliferation during development and regeneration

The regulation of cardiomyocyte proliferation is important for heart development and regeneration. The proliferation patterns of cardiomyocytes are closely related to heart morphogenesis, size, and functions. The proliferation levels are high during early embryogenesis; however, mammalian cardiomyocytes exit the cell cycle irreversibly soon after birth. The cell cycle exit inhibits cardiac regeneration in mammals. On the other hand, cardiomyocytes of adult zebrafish and probably newts can proliferate after cardiac injury, and the hearts can be regenerated. Therefore, the ability to reproliferate determines regenerative ability. As in other cells, the relationship between proliferation and differentiation is very interesting, and is closely related to cardiac development, regeneration and homeostasis. In this review, these topics are discussed.     

Electron microscopy and 3D reconstruction of F-actin decorated with cardiac myosin-binding protein C (cMyBP-C)

Myosin-binding protein C (MyBP-C) is an ∼ 130-kDa rod-shaped protein of the thick (myosin containing) filaments of vertebrate striated muscle. It is composed of 10 or 11 globular 10-kDa domains from the immunoglobulin and fibronectin type III families and an additional MyBP-C-specific motif. The cardiac isoform cMyBP-C plays a key role in the phosphorylation-dependent enhancement of cardiac function that occurs upon β-adrenergic stimulation, and mutations in MyBP-C cause skeletal muscle and heart diseases. In addition to binding to myosin, MyBP-C can also bind to actin via its N-terminal end, potentially modulating contraction in a novel way via this thick-thin filament bridge. To understand the structural basis of actin binding, we have used negative stain electron microscopy and three-dimensional reconstruction to study the structure of F-actin decorated with bacterially expressed N-terminal cMyBP-C fragments. Clear decoration was obtained under a variety of salt conditions varying from 25 to 180 mM KCl concentration. Three-dimensional helical reconstructions, carried out at the 180-mM KCl level to minimize nonspecific binding, showed MyBP-C density over a broad portion of the periphery of subdomain 1 of actin and extending tangentially from its surface in the direction of actin's pointed end. Molecular fitting with an atomic structure of a MyBP-C Ig domain suggested that most of the N-terminal domains may be well ordered on actin. The location of binding was such that it could modulate tropomyosin position and would interfere with myosin head binding to actin.     

Cardiospheres and tissue engineering for myocardial regeneration: potential for clinical application

Tissue engineering is an increasingly expanding area of research in the cardiovascular field that involves engineering, chemistry, biology and medicine. Cardiac tissue engineering (CTE) aims to regenerate myocardial damage by combining cells, matrix, biological active molecules and physiological stimuli. The rationale behind CTE applications is that in order to regenerate the ventricular wall after a myocardial infarction it is necessary to combine procedures that regenerate both cardiomyocytes and the extracellular matrix. The application of (stem) cells together with a matrix could represent an environment protected from the inflammatory and pro-apoptotic signals, a stemness/survival reservoir slowly releasing cells and factors promoting tissue regeneration and angiogenesis. This review will focus on the applications and advantages that CTE application could offer compared to conventional cell therapy.     

用心脏舒张期与收缩期时限比值评估青少年心脏功能

目的：观察青少年在安静状态及最大运动量状态下心脏舒张期时限与收缩期时限比值（D/S）的变化情况,并运用该指标对青少年心脏功能的评估进行探讨。方法：选取重庆市主城区中学309名（男159名,女150名）青少年为研究对象,受试者完成最大运动量的台阶运动,在安静状态和运动后即刻进行D/S比值的测试。根据安静状态D/S值的大小范围将受试者心脏功能分级为优（ D/S≥2）、良（1.5≤D/S<2）、中（1≤D/S<1.5）、差（D/S<1）。结果：安静状态下男生心脏功能评定为优、良、中、差的占比分别为： 7.5%、49.1%、 40.9%、2.5%;女生分别为： 5.3%、48.0%; 44.7%、2.0%。运动后男、女青少年D/S值都明显下降,但心脏功能评定等级高的受试者运动后D/S仍高于等级低的受试者。结论：本次研究的青少年虽有过半心脏功能处于健康状态,但处于亚健康状态的比例较高,有少部分学生心脏功能较差,其心脏健康应得到高度重视;心脏功能等级越高的学生运动后心脏供血时间越长,其心脏功能更好。应用D/S值可以有效评估青少年心脏供血时限的相关情况;对青少年心脏功能进行分级可以针对不同分级群体制定有针对性的运动训练,同时预防心脏安全事故的出现。该评估方法操作简单、客观,可作为一种日常的心脏监测手段在学校普及。     

Cathepsin K knockout alleviates aging‐induced cardiac dysfunction

Aging is a major risk factor for cardiovascular disease. It has previously been shown that protein levels of cathepsin K, a lysosomal cysteine protease, are elevated in the failing heart and that genetic ablation of cathepsin K protects against pressure overload‐induced cardiac hypertrophy and contractile dysfunction. Here we test the hypothesis that cathepsin K knockout alleviates age‐dependent decline in cardiac function. Cardiac geometry, contractile function, intracellular Ca²⁺ properties, and cardiomyocyte apoptosis were evaluated using echocardiography, fura‐2 technique, immunohistochemistry, Western blot and TUNEL staining, respectively. Aged (24‐month‐old) mice exhibited significant cardiac remodeling (enlarged chamber size, wall thickness, myocyte cross‐sectional area, and fibrosis), decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca²⁺ release compared to young (6‐month‐old) mice, which were attenuated in the cathepsin K knockout mice. Cellular markers of senescence, including cardiac lipofuscin, p21 and p16, were lower in the aged‐cathepsin K knockout mice compared to their wild‐type counterpart. Mechanistically, cathepsin K knockout mice attenuated an age‐induced increase in cardiomyocyte apoptosis and nuclear translocation of mitochondrial apoptosis‐inducing factor (AIF). In cultured H9c2 cells, doxorubicin stimulated premature senescence and apoptosis. Silencing of cathepsin K blocked the doxorubicin‐induced translocation of AIF from the mitochondria to the nuclei. Collectively, these results suggest that cathepsin K knockout attenuates age‐related decline in cardiac function via suppressing caspase‐dependent and caspase‐independent apoptosis.     

在生理学研究中如何正确把握试验设计三要素

目的：为从事生理学研究的科研工作者制订科学完善的试验设计方案提供一些有效的技术方法。方法：通过正面阐述三要素和正确把握每个要素的关键点;再通过分析已发表的学术论文中未妥善把握三要素的案例,为生理学研究工作者在制订课题设计方案时能正确把握三要素提供具有可操作性的方法。结果：呈现出试验设计三要素的具体内容,即"受试对象"、"影响因素"和"试验效应",并且,为如何正确把握每个要素提供具体措施。结论：试验设计的三要素是从事试验研究的"物质基础",正确把握它们是制订出科学完善试验设计方案的重要环节之一。     

慢性缺氧对大鼠心室功能和ATP酶活性的影响

将大鼠置于不同模拟海拔高度低压舱内4d,观察其左、右心室功能代偿与失代偿的某些生物化学基础。结果表明,5000m中度缺氧4d使左、右心室功能、重量、心肌蛋白含量及Ca~(2 )-ATP酶活性均有不同程度的增高。提示机体在整体、心脏器官及心肌细胞分子各个水平的代偿机制均有加强。8000m重度缺氧4d后,左室重量增加,dp/dt_(max)与蛋白含量均下降,肌原纤维ATP酶活性则保持中度缺氧的代偿水平,提示左心功能似已受到损害。与此同时,右室蛋白含量虽也明显减少,但其ATP酶活性则继续增高,dp/dt_(max)未出现下降,表明右心功能仍具有相当的代偿能力。从而支持我们关于在短期内因供氧严重不足而造成的左室心肌的直接损伤作用大于右室心肌的推论。     

Turning regenerative technologies into treatment to repair myocardial injuries

Regenerative therapies including stem cell treatments hold promise to allow curing patients affected by severe cardiac muscle diseases. However, the clinical efficacy of stem cell therapy remains elusive, so far. The two key roadblocks that still need to be overcome are the poor cell engraftment into the injured myocardium and the limited knowledge of the ideal mixture of bioactive factors to be locally delivered for restoring heart function. Thus, therapeutic strategies for cardiac repair are directed to increase the retention and functional integration of transplanted cells in the damaged myocardium or to enhance the endogenous repair mechanisms through cell-free therapies. In this context, biomaterial-based technologies and tissue engineering approaches have the potential to dramatically impact cardiac translational medicine. This review intends to offer some consideration on the cell-based and cell-free cardiac therapies, their limitations and the possible future developments.     

Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart

Cannabinoid receptor type 2(CB2)activation is recently reported to promote proliferation of some types of resident stem cells(e.g.,hematopoietic stem/progenitor cell or neural progenitor cell).Resident cardiac progenitor cell(CPC)activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction(MI).This study aims to explore the role and possible mechanisms of CB2receptor activation in enhancing myocardial repair.Our results revealed that CB2receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation.AM1241 also decreased serum levels of MDA,TNF-αand IL-6 after MI.In addition,AM1241 can ameliorate left ventricular ejection fraction and fractional shortening,and reduce fibrosis.Moreover,AM1241 treatment markedly increased p-Akt and HO-1 expression,and promoted Nrf-2 nuclear translocation.However,PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241.In conclusion,AM1241 could induce myocardial regeneration and improve cardiac function,which might be associated with PI3K/Akt/Nrf2 signaling pathway activation.Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.