狗左冠状动脉结扎后左、右心室和肺循环功能的动态演变及其相互关系

用麻醉开胸狗,观察了左冠状动脉前降支(LAD)结扎后2小时内,左,右心室舒缩性能、泵功能及肺循环压力和阻力的动态变化,并分析其相互关系。结扎LAD所造成的心肌缺血范围占左心室(LV)重量的35.2±1.4%。LAD结扎后,依次出现LV舒缩性能、肺动脉压、左、右心室泵功能、LV收缩性船、右心室(RV)舒张性能和肺血管阻力的改变,而RV收缩性能则无明显变化。结果表明,较大范围的LV心肌梗塞(MI)早期,LV功能降低可直接导致RV舒张性能降低,还可直接和通过肺循环压力和阻力升高间接使RV泵功能降低。但对RV收缩性能无明显影响。因子分析提示,LV收缩性能与两心室泵功能的改变是LVMI后心功能改变的主要方面;依次为两心室舒张性能和肺循环功能的改变。     

低氧和低氧游泳大鼠心肌糖原含量与右室功能的变化

目的：观察慢性低氧及低氧游泳大鼠心肌糖原含量的变化，探讨其与右心舒缩功能升降的关系。方法：采用低压舱模拟海拔5000 m连续低氧及低氧游泳大鼠模型，用比色法测定其心肌糖原含量；用右心导管法经RM-6000生理多导记录仪记录右心舒缩功能指标。结果：大鼠心肌糖原含量在低氧早期即显著下降，随低氧时间的延长，呈较明显进一步下降的趋势，而右心功能则逐渐增强；低氧游泳组大鼠右心功能明显增强，其心肌糖原含量接近平原对照水平，显著高于单纯低氧组。结论：大鼠在低氧条件下适量作功（游泳），可能有利于机体的低氧适应。     

广西壮族自治区体循环血管阻力异常人群的分布及心脏功能分析

目的 分析体循环血管阻力(SVR)异常在健康人群中的分布特点及心脏功能参数的相关变化。方法 用Bioz．com数字化无创血液动力学监护仪，观察919名健康人体循环血管阻力及平均动脉压(MAP)、心输出量(CO)、心脏指数(CI)、搏出量(SV)、搏出指数(SI)、左心做功量(LCW)等心功能参数。结果 体循环血管阻力异常在低年龄段和高年龄段发生率均较高；女性显著高于男性(P <0.001)。相关因素分析显示，体循环血管阻力与平均动脉压（MAP）、脉压(PP)和左心射血时间(LVET)呈正相关；而与心输出量、心脏指数、搏出量、搏出指数、左心做功量及动脉顺应性(AC)呈负相关。结论 广西壮族人群体循环血管阻力异常与年龄、性别及血压水平密切相关，体循环血管阻力升高，心输出量和心指数降低，心脏泵功能减弱。     

三七总甙对大鼠烧伤后心肌细胞膜离子泵活性的影响

心肌细胞膜Na -K 泵、Ca2 -Mg2 泵通过消耗ATP,调节离子转运,直接参与心肌舒缩过程的调控;红细胞膜上的Na -K 泵与左心室收缩功能之间有高度相关性,而Ca2 -Mg2 泵则与心脏舒张及收缩功能均显著相关。本室既往研究发现大鼠在严重烧伤后心功能下降,三七总皂苷(PNS)能有效改善烧伤后心功能。为观察PNS对烫伤大鼠红细胞及心肌细胞     

双心室辅助对缺血性左右心功能不全血流动力学影响的实验研究

比较在缺血性左右心功能不全时左心辅助和双心室辅助对血流动力学的不同影响 ,为自制气动隔膜泵(罗叶泵 )的临床应用提供实验依据。采用 8只健康成年犬 ,植入左心辅助装置和右心辅助装置。结扎左前降支 ,3mins后在窦房结支发出处远侧端结扎右冠状动脉 ,以建立缺血性左右心功能不全的动物模型。先行左心辅助 5mins,再行双心室辅助。分别记录中心静脉压 ,心输出量 ,平均动脉压 ,肺动脉压 ,肺毛细血管楔压等血流动力学指标。结果表明 :双心室辅助时心输出量显著上升 (0 .82 2± 0 .0 9L / min vs 1.33± 0 .12 L / m in,P<0 .0 1)与正常对照值相比无显著差异 ;平均动脉压上升达正常范围 (37.4± 8.8mm Hg vs 84.2± 9.7mm Hg,P<0 .0 1) ;中心静脉压显著下降 (14.6± 2 .3cm H2 O vs 4.2± 1.5 cm H2 O,P<0 .0 1) ;肺动脉压无显著性变化 ;肺毛细血管楔压下降 (14± 3.9vs 1.6± 0 .9mm Hg,P<0 .0 1)。结论是全心功能不全时 ,单纯应用左心辅助并不能有效地改善血流动力学状况 ,应用双心室辅助可提高心输出量和动脉压至正常水平 ,可最大限度地减少心脏作功 ,降低氧耗 ,促进心肌组织的修复和代谢。因此 ,在左右心功能明显受损对药物和主动脉内球囊反搏 (IABP)治疗无效时 ,单行左心辅助应慎重 ,双心室辅助是推荐     

阿霉素性心肌病心脏收缩性、舒张性和顺应性的动态演变及其对心泵功能的影响

Wistar大鼠90只,分为4组,采用多次静脉注射小剂量阿霉素(ADR)造成不同程度的心肌病变和心功能功不全,用心导管法动态观察左室收缩性、舒张性、顺应性和心泵功能的变化及诸变化之间的关系和其相互作用。结果表明,与对照组相比,随着ADR累积量的增加(4-8-16mg/kg),左室收缩性(指标:dp/dtmat、     

缺氧性肺动脉高压的发展与左右心功能变化关系的进一步探讨

我们曾在“缺氧性肺动脉高压的发展与心输出量动态变化的关系”中报道:大鼠在模拟5,000m高度的低压舱内连续减压缺氧4、10、20天,其右心室收缩压RVP(相当于肺动脉收缩压)、右室±(dp/dt)max(反映心肌舒缩功能)、心输出量CO,每搏量SV和心指数CI均随缺氧时间的延长而逐步升高,左室压LVP与左室±(dp/dt)max则无明显改变。本文延     

心脏局部肾素—血管紧张素系统在大鼠容量负荷性心肌肥大中的作用

本文采用大鼠腹腔动—静脉瘘(ACF)伴左肾切除模型,研究容量超负荷时,心脏和循环肾素—血管紧张素系统(RAS)的变化及其与心肌肥大的关系。结果发现,ACF伴左肾切除(ACF NT)大鼠,在心肌肥大的同时,左、右心室的血管紧张素Ⅱ(AngⅡ)含量及血管紧张素转换酶(ACE)活性均显著升高,尽管其血浆AngⅠ、Ⅱ和肾素活性都维持在一个较低水平。提示:(1)心脏局部RAS可能在容量负荷性心肌肥大早期起着不容忽视的作用;(2)心肌AngⅡ的升高与心肌ACE活性增高有关;(3)循环RAS在容量负荷性心肌肥大中不起主要作用。     

376例慢性疾患具有低排高阻时微循环变化

我们在2681例慢性疾病患者中,观察到376例病人有心输出量降低,外周阻力升高,这些病人每分心输出量(CO)平均3.71(L/min)、心指数(Cl)平均2.43(L/mln/m~2)和每搏输出量(SV)平均48.7(ml)均低于正常水平并伴有左心室有效泵力和左心室有效泵力指数下降,表明有心泵功能减弱。总外周阻力(RT)平均为     

高雌激素血症对雌性心肌梗塞大鼠心肌舒缩性能的影响

本文研究了高雌激素血症对雌性心肌梗塞(MI)大鼠心肌舒缩性能的影响。结果:(1)MI组血浆雌二醇(E_2)先略升高而后降低,雌二醇处理MI组(MIE_2)血浆雌二醇明显升高。(2)MIE_2组心肌纤维直径比对照假手术组(CS)及MI组显著增大(10.65±0.59 VS 7.65±0.40及10.15±0.54gm,P<0.001,<0.02)。(3)两MI组的LVSP、±dp/dt max均显著降低,T-值明显延长,尤以MIE_2组更为显著(10.5±4.1 VS 6.2±4.6ms,P<0.02)。(4)两MI组动脉压显著降低,HR减慢,LVET延长;在9天观测点,MIE_2组的HR仍较MI组显著减慢、LVET明显延长。提示高雌激素血症可使雌性心肌梗塞大鼠心肌舒缩性能降低。     

Beneficial effects of a novel ultrapotent poly(ADP-ribose) polymerase inhibitor in murine models of heart failure

Overactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of cell dysfunction and tissue injury in various pathophysiological conditions associated with oxidative and nitrosative stress, including myocardial reperfusion injury, heart transplantation, diabetic cardiomyopathy and chronic heart failure. In recent studies, we have demonstrated the beneficial effects of a novel ultrapotent PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction and remodeling in rat model of advanced aging-associated chronic heart failure and in a mouse model of heart failure induced by aortic banding. In the current study, we have investigated the effect of INO-1001 on the development of heart failure induced by permanent ligation of the left anterior descending coronary artery, heart failure induced by doxorubicin and acute myocardial dysfunction induced by bacterial endotoxin. In the coronary ligation model, a significantly depressed left ventricular performance and impaired vascular relaxation of aortic rings were found, and PARP inhibition significantly improved both cardiac function and vascular relaxation. In the doxorubicin model, a single injection of doxorubicin induced high mortality and a significant decrease in left ventricular systolic pressure, +dP/dt, -dP/dt, stroke volume, stroke work, ejection fraction and cardiac output. Treatment with the PARP inhibitor reduced doxorubicin-induced mortality and markedly improved cardiac function. PARP inhibition did not interfere with doxorubicin's antitumor effect. In the endotoxin model of cardiac dysfunction, PARP inhibition attenuated the suppression of myocardial contractility elicited by endotoxin. The current data strengthen the view that PARP inhibition may represent an effective approach for the experimental therapy of various forms of acute and chronic heart failure.     

Pathophysiology of heart failure

Heart failure is a leading cause of mortality and morbidity in Western countries. Common etiology is mostly represented by ischemic and hypertensive heart disease. Clinically, heart failure can be defined as an impaired cardiac performance, unable to meet the energy requirements of the periphery. Pathophysiologically, the clinical onset of heart failure symptoms already represents an advanced stage of disease when compensatory mechanisms triggered by the underlying decrease in contractility are no longer capable of maintaining adequate cardiac performance during exercise and, subsequently, under resting conditions. Independent of its underlying etiology, cardiac failure is always characterized by an impairment in the intrinsic contractility of myocytes. As a consequence of reduced contractility, a number of central and peripheral compensatory mechanisms take place that are capable of effectively counteracting reduced intravascular intrinsic performance for a long period of time. Among them, recruitment of preload reserve, enhanced neurohormonal stimulation and cardiac hypertrophy are the most important. All of them, however, also carry unfavorable effects that contribute to further deterioration of cardiac function. In fact, increased end-diastolic volume determines increased wall stress that further reduces systolic performance; sympathetic and angiotensin stimulation increases peripheral resistance and contributes to increase volume expansion; hypertrophic myocytes demonstrate impaired intrinsic contractility and relaxation, and hypertrophy causes a clinically relevant deterioration of ventricular relaxation and compliance that substantially participates in increased end-diastolic pressure, and, therefore, to limited exercise performance. Diastolic dysfunction usually accompanies systolic dysfunction, although in some cases it may represent the prevalent mechanism of congestive heart failure in patients in whom systolic performance is preserved. Biological causes of reduced contractility in heart failure are not completely elucidated. Changes in myosin composition and in sarcoplasmic ATPase activity, causing reduced Ca2+ availability during contraction, have been reported, although their exact contribution is not clear. Recently, impaired endothelial function has also been described in heart failure, and new appealing hypotheses have been made regarding the causative role of circulating cytokines like tumor necrosis factor in the pathogenesis of heart failure.     

Axial flow pump treatment during myocardial depression in calves: an invasive hemodynamic and echocardiographic tissue Doppler study

The aim of this study was to investigate flow characteristics and myocardial function after implantation of an axial pump left ventricular assist device while varying afterload and during progressive myocardial depression. Ten calves were included, seven of which fulfilled the protocol. Invasive hemodynamic monitoring and echocardiography with color-coded systolic tissue Doppler velocity (TD velocity) were used during prepump conditions, at three different pump speeds, during modification of the systemic vascular resistance (SVR), and during increasing degrees of beta-blockade. The TD velocity decreased with the myocardial function whereas left ventricular size, fractional shortening, and pump speed did not correlate significantly with the TD velocity. The TD velocity correlated significantly with native stroke volume, heart rate, SVR and cardiac output but none of these alone could explain more than 20% of the changes in TD velocity. The axial flow pump studied is effective in unloading the severely depressed heart and has a high capacity for maintaining an adequate cardiac output, regardless of differing hemodynamic conditions, pump speed or decreasing LV function. Echocardiography with volumetric rendering and TD velocity imaging are valuable tools for monitoring and quantifying residual myocardial function during pump treatment.     

The enabler cannula pump: a novel circulatory support system.

BACKGROUND: The enabler circulatory support system is a catheter pump which expels blood from the left or right ventricular cavity and provides pulsatile flow in the ascending aorta or pulmonary artery. It is driven by a bedside installed pulsatile driving console. The device can easily be implanted by a minimal invasive approach, similar to the Hemopump. PURPOSE: To demonstrate the hemodynamic performance of this new intracardiac support system. METHODS: In a series of 9 sheep, hemodynamic evolutions were recorded in various conditions of myocardial contractility (the non-failing, the moderately failing and the severely failing heart). Heart failure was induced by injection of microspheres in the coronary arteries. RESULTS: Introduction of the cannula through the aortic valve was feasible in all cases. Pump flow by the enabler was gradually increased to a maximum of 3.5 L/min. Diastolic (and mean) aortic blood pressure is significantly increased in the non-failing and moderately failing condition (counterpulsation mode). In heart failure, cardiac output is significantly increased by the pump (p < 0.0001). A drop in left atrial pressure (indicating unloading) is achieved in all conditions but reaches significant levels only during heart failure (p=0.0068). CONCLUSIONS: This new circulatory support system contributes to stabilization of the circulation in the presence of cardiac unloading. In heart failure it actually supports the circulation by increasing cardiac output and perfusion pressure.     

Right ventricular function in rats with hypoxic pulmonary hypertension

The function of the hypertrophic right ventricle (RV) was studied in adult rats with hypoxic pulmonary hypertension induced by intermittent high-altitude (IHA) exposure. The isolated RV working heart preparation that was employed enabled us to estimate ventricular contractile and pump performance under controlled loading conditions. In rats exposed to IHA hypoxia the elevated RV systolic pressure and maximum rate of pressure development were observed at various levels of preload or afterload. The peak indices of mechanical performance were almost doubled in these animals when compared with the normoxic group, while the index of contractility remained unchanged. Maximum ventricular performance was found to be a linear function of the relative RV weight. No evidence of RV pump dysfunction was detected in rats exposed to IHA; moreover, the ability of the ventricle to maintain cardiac output against increased pulmonary resistance was markedly improved. The prevention of tricuspid regurgitation by using an artificial valve did not influence the functional curves and the peak ventricular performance. The regression of hypertrophy was accompanied by a reversal of ventricular function to control values, except for the persisting slight increase of peak RV pressure. It may be concluded that the increase of the RV mass in IHA-exposed rats serves to improve maximum ventricular performance, which aids in overcoming an elevated pulmonary resistance without disturbing the pump function.     

Effects of histamine H1- and H2-receptor antagonists on cardiovascular function during systemic anaphylaxis in guinea pigs

The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction, and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A₂ and leukotrienes, are responsible for anaphylactic coronary constriction and negative inotropic effects. The cardiac effects of anaphylactic histamine release are related to the stimulation of two antagonistic receptor types. Histamine induces atrioventricular conduction delay and constriction of the epicardial coronary vessels via H₁-receptor stimulation. H₂-receptors, however, mediatecoronary vasodilation and an increase in heart rate and myocardial contractility. It may therefore be concluded that administration of histamine H₂-receptor antagonists is disadvantageous. During anaphylactic states, the cardiodepressive effects of the other mediators of anaphylaxis are unmasked, resulting in a sustained coronary constriction and impairment of myocardial contractility. To verify this speculation, we investigated the effects of H₁- and H₂-receptor antagonists on cardiovascular function of guinea pigs during systemic anaphylaxis.In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed administration of the antigen induced severe cardiac dysfunction. Within a few minutes, cardiac output markedly decreased and left ventricular end-diastolic pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of an atrioventricular block. After 4 min, blood pressure rapidly declined. All animals died within 12 min. Pretreatment with the selective H₁-receptor antagonist astemizol (5 mg/kg i.v.) delayed the onset of myocardial ischemia, arrhythmias and cardiac pump failure. After 10 min, however, left ventricular contractility and blood pressure steadily declined, leading to severe hypotension within 30 min. In the case of a pretreatment with astemizol (5 mg/kg i.v.) and the H₂-receptor antagonist famotidine (10 mg/kg i.v.), no relevant changes of cardiovascular function were seen compared to pretreatment with astemizol alone. It is therefore concluded that endogenous histamine, via H₁-receptor stimulation plays an important part during the early phase of systemic anaphylaxis, whereas mediators other than histamine are involved at a later stage of the process. Furthermore, H₂-receptor-mediated effects are of minor importance in cardiovascular manifestation of anaphylaxis. Pretreatment with H₂-receptor antagonists has no detrimental effects on cardiovascular function during anaphylactic reactions in guinea pigs underin vivo conditions.Supported by grant Fe250/1-1 from the Deutsche Forschungsgemeinschaft (DFG).     

Effects on dogs of surface-induced hypothermia and rewarming on the right heart function and pulmonary circulation

Hypothermia is commonly found in accidents on land and at sea, yet its pulmonary circulatory effects have not been studied before. To study the effects of hypothermia on the right heart function and pulmonary circulation, cardiac catheterization was carried out on nine anaesthetized beagle dogs. The dogs were cooled between ice bags until the temperature in the pulmonary artery was 25°C and then rewarmed using a heating box especially constructed for this purpose. Heart rate decreased significantly (P < 0.01) during cooling. Cardiac output also diminished mainly because of decreased heart rate. Total pulmonary resistance increased in the cold (P < 0.05) and returned to the initial level during rewarming. The peak rate of increase in pressure (dP/dt_max) of the right ventricular pressure curve did not show any significant change. Retardation in relaxation in hypothermia was indicated by an increase (P < 0.01) in the peak negative dP/dt of the right ventricular pressure curve. According to our results, the contraction rate did not change, but the relaxation rate decreased significantly during cooling. No signs of heart failure were observed and all parameters returned to normal during rewarming. In conclusion, right ventricular function was not compromized even during deep hypothermia. Accepted: 19 November 1999     

Effects of renal sympathetic denervation on cardiac systolic function after myocardial infarction in rats

This study investigated the therapeutic effects of renal denervation on cardiac systolic function after myocardial infarction (MI) in rats and the mechanism involved. Fifty male SD rats were randomly assigned to the sham group (n = 15), the MI group (n = 20), and the MI plus renal denervation group (n = 15). MI was established through thoracotomic ligation of the anterior descending artery. Renal denervation was achieved by laparotomic stripping of the renal arterial adventitial sympathetic nerve, approximately 3 mm from the abdominal aorta. Left ventricular function and hemodynamics were measured several weeks following MI. The left ventricular systolic function of the MI group was significantly reduced and the systolic blood pressure (SBP) remarkably declined. In rats with MI treated with renal denervation, the left ventricular ejection fraction (EF), fractional shortening (FS) and SBP markedly improved compared with the MI group. However, heart rate and fibrosis decreased significantly. These findings suggest that renal denervation has therapeutic effects on post-MI cardiac dysfunction. These effects are associated with increased left ventricular ejection fraction (LVEF) and SBP, as well as reduced heart rate and fibrosis. This may represent a new approach to the treatment of post-MI remodeling and subsequent heart failure.     

Heart functional responses to pressure overload in exercised and sedentary rats.

Female rats that had been subjected to a moderate treadmill running program were compared with sedentary animals on the basis of heart weight, selected biochemical measurements, and heart function. Exercised animals maintained normal growth rate, and cardiac hypertrophy was not present. Left ventricular RNA, DNA, and cytochrome c levels were unchanged. Heart functional measurements obtained in situ were similar in sedentary and exercised animals under control conditions. When subjected to sustained (1-3 days) aortic constriction pressure overload, exercised animals maintained or increased myocardial contractility. Contractility was depressed in sedentary animals. Both sedentary and exercised animals increased left ventricular end diastolic pressure without changing contractility during acute (1-3 min) pressure overload. However, exercised animals were able to fully regain normal cardiac output when the acute overload was relieved. Cardiac output remained approximately 10% below control in sedentary animals. The improved ability of previously exercised animals to withstand pressure overload appears to be due to alterations in adaptation rather than preliminary augmentation of metabolism or function.     

Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats

Background/AimsGalectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy.MethodsRats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy.ResultsGalectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls.ConclusionIncreased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.