Myocardial Function and Lipid Metabolism in the Chronic Alcoholic Animal

In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium.To evaluate myocardial lipid metabolism, [1-(14)C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced (14)CO(2) production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [(14)C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic.     

超声心动图研究正压通气对犬心功能的影响及其机制

目的观察正压通气时心内瓣口血流速度和左、右心功能的变化,研究正压通气影响血流动力学机制的新理论。方法11条杂种犬,用超声心动图测定正压通气时心内各瓣口的血流速度,右室、左室每搏量,左室容积和射血分数的变化。结果三尖瓣和肺动脉瓣口血流速度正压吸气相减低,呼气相增加;二尖瓣和主动脉瓣口血流速度变化与之相反(P<0.05)。与自主呼吸相比,正压吸气时,右室每搏量减少,左室舒张末和收缩末容积减小,射血分数降低(P<0.05)。结论正压通气使室间隔趋于右移,同时,肺血管床回心血量增加,但与自主呼吸时相比,腔静脉回心血量相对减少,故心功能降低。     

Effects of dopamine, (+/-)-dobutamine and the (+)- and (-)-enantiomers of dobutamine on cardiac function in pithed rats

The effects of dopamine, (+/-)-dobutamine (racemic mixture) and the (+)- and (-)-enantiomers of dobutamine on myocardial function were evaluated in pithed rats. Dopamine and (+/-)-dobutamine produced effects on cardiac function in pithed rats that were qualitatively similar to those reported for these compounds in humans. The increase in cardiac output produced by dopamine and (+/-)-dobutamine was due mainly to an increase in stroke volume, with increases in heart rate contributing to a significant but lesser degree. For both dopamine and (+/-)-dobutamine, the increase in stroke volume appears to result from an increase in myocardial contractility as assessed by increases in left ventricular (LV) dp/dt. Dopamine produced a marked increase in mean arterial blood pressure, whereas (+/-)-dobutamine only modestly increased blood pressure. The (-)-enantiomer of dobutamine, which possesses mainly alpha-1 adrenoceptor agonist activity, produced dose-dependent increases in cardiac output, stroke volume, LVdp/dt and mean arterial blood pressure, but did not significantly increase heart rate except at high doses. Thus, the increase in cardiac output produced by (-)-dobutamine was derived almost exclusively from an augmentation in stroke volume resulting from an increase in myocardial contractility. In contrast, (+)-dobutamine, which possesses predominantly beta-1 and beta-2 adrenoceptor agonist activity, elicited only a modest increase in cardiac output which was due both to an increase in heart rate and stroke volume. Mean arterial blood pressure was not significantly affected by (+)-dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function.     

AV Pacing and LV Performance

Five patients with impaired left ventricular function (LV) and implanted AV sequential pacemakers underwent serial radionuclide angiograms. The goal was a non-invasive evaluation of the rapid changes in left ventricular performance elicited by rate, pacing mode and AV interval manipulation. End diastolic volume, end systolic volume, stroke volume and cardiac output were increased by AV sequential pacing in comparison with ventricular pacing at 70 beats per minute. No significant change in ejection fraction and blood pressure were noted with changing AV sequential pacing rates at usual pacing rates. Our data suggest that a short A V interval (150 ms) improved LV performance more than a long AV interval (250 ms). A non-invasive technique to optimize left ventricular performance on an acute basis by varying heart rate, AV interval and pacing mode with the implanted AV sequential pacemaker is feasible and may be useful in selective clinical situations.     

Ex vivo perfusion of the swine heart as a method for pre-transplant assessment

We describe a cost-effective, reproducible circuit in a porcine, ex vivo, continuous warm-blood, bi-ventricular, working heart model that has future possibilities for pre-transplant assessment of marginal hearts donated from brain stem dead donors and hearts donated after circulatory determination of death (DCDD). In five consecutive experiments over five days, pressure volume loops were performed. During working mode, the left ventricular end systolic pressure volume relationship (LV ESPVR) was 23.1±11.1 mmHg/ml and the LV preload recruitable stroke work (PRSW) was 67.8±7.2. (Standard PVAN analysis software) (Millar Instruments, Houston, TX, USA) All five hearts were perfused for 219±64 minutes and regained normal cardiac function on the perfusion system.They displayed a significant upward and leftward shift of the end systolic pressure volume relationship, a significant increase in preload recruitable stroke work and minimal stiffness. These hearts could potentially be considered for transplantation. The circuit was effective during reperfusion and working modes whilst proving to be successful in maintaining cardiac function in excess of four hours. Using an autologous prime of approximately 20% haematocrit (Hct), electrolytes and blood gases were easy to control within this period using standard perfusion techniques.     

65例老年心肌梗死合并心律失常患者早期康复护理干预对其心功能及预后的影响分析

目的分析早期康复护理干预对老年心肌梗死合并心律失常患者心功能及近期预后情况的影响。方法选择本院收治的65例老年心肌梗死合并心律失常患者,将其随机分为对照组(32例)和观察组(33例),对照组患者采用传统心肌梗死康复法对患者实施常规康复护理,观察组患者采用早期康复护理干预。比较2组患者入组前、入组后4周、3个月、6个月后收缩压、Killip分级、心率、左室收缩功能、每博量,比较2组患者入组后4周、3个月、6个月的运动耐力(步行试验、踏车实验),比较2组患者入组后6个月内心律失常率、再梗死率、病死率。结果 2组患者入组前左室射血分数、Killip分级、心率、左室压力上升最大速率、每博量比较差异无统计学意义(P0.05);随着时间的推移,2组患者的左室射血分数、Killip分级、心率、左室压力上升最大速率、每博量均较入组前有显著改善,每一个观察时间点,观察组的左室射血分数、左室压力上升最大速率、每博量、均显著高于对照组,Killip分级、心率均小于对照组,上述指标组间比较差异有统计学意义(P0.05);观察组患者入组后4周、3个月、6个月步行试验完成率、踏车实验完成率均显著高于对照组,观察组患者入组6个月后心律失常率、心急再梗死率及病死率均显著低于对照组,组间比较差异有统计学意义(P0.05)。结论早期康复护理干预可有效改善老年心肌梗死合并心律失常患者的心功能,改善患者预后质量。     

Contrast enhanced echocardiographic follow-up of cardiac remodeling and function after myocardial infarction in rats

Echocardiography is a reliable and commonly used method to examine cardiac diseases. Recent employment of modern technologies provides new opportunities to study left ventricular (LV) remodeling after myocardial infarction (MI) also in small rodents. LV volumes as most important prognostic parameters can be estimated by noncontrast enhanced echocardiography in rats from M-mode or single cross sections only. In this study, contrast enhanced echocardiography and volume measurements by the biplane method of discs (Simpson's rule) were applied in rats to monitor remodeling and function after MI. MI was induced in female Sprague-Dawley rats (n = 26 for MI, and n = 16 for sham). LV remodeling and heart function were serially studied by contrast enhanced echocardiography for 12 to 16 wk. At the end of the observation periods hemodynamic data were additionally measured by left and right heart catheterization. LV end systolic volume (LVESV) measured by biplane method of discs correlated best with LV developed pressure as indicator for severely impaired heart function. Interestingly, LV end systolic area (LVESA) from native short axis view correlated well with LVESV (R(2) = 0.93) and was the second best predictor for depressed heart function. Moreover, left atrial size was a powerful indicator of severely impaired heart function whereas ejection fraction or fractional area change were primarily related to infarct size. In conclusion, contrast enhanced echocardiography in rats is feasible and an economical method to study time-dependent LV remodeling and deterioration of contractile function after MI.     

Improved function of the failing rat heart by regulated expression of insulin-like growth factor I via intramuscular gene transfer

Current methods of gene transfer for heart disease include injection into heart muscle or intracoronary coronary delivery, approaches that typically provide limited expression and are cumbersome to apply. To circumvent these problems, we selected a transgene, insulin-like growth factor-I (IGF-I), which may, in theory, have favorable effects on heart function when secreted from a remote site. We examined the feasibility and efficacy of skeletal muscle injection of adeno-associated virus 5 encoding IGF-I under Tet regulation (AAV5.IGFI-tet) to treat heart failure. Myocardial infarction (MI) was induced in rats by coronary occlusion; 1 week later, rats with impaired left ventricular (LV) function received 2×10(12) genome copies (GC) of AAV5.IGFI-tet in the anterior tibialis muscle, and 4 weeks later, were randomly assigned to receive doxycycline in drinking water to activate IGF-I expression (IGF-On; n=10), or not to receive doxycycline (IGF-Off; n=10). Ten weeks after MI (5 weeks after activation of IGF-I expression), LV size and function were assessed by echocardiography and physiological studies. IGF-On rats showed reduced LV end-systolic dimension (p=0.03) and increased LV ejection fraction (p=0.02). In addition, IGF-On rats showed, before and during dobutamine infusion, increases in cardiac output (p=0.02), stroke work (p=0.0001), LV + dP/dt (p<0.0001), LV relaxation (LV - dP/dt; p=0.03), and systolic arterial blood pressure (p=0.0003). Mean arterial pressure and systemic vascular resistance were unchanged. Activation of IGF-I expression reduced cardiac fibrosis (p=0.048), apoptosis (p<0.0001), and caspase-3/7 activity (p=0.04). Serum IGF-I was increased 5 weeks after transgene activation (p=0.008). These data indicate that skeletal muscle injection of AAV5.IGFI-tet enables tetracycline-activated expression, increases serum IGF-I levels, and improves function of the failing heart.     

Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibitor administration

OBJECTIVE: The goal of this study was to determine whether treatment with an aldose reductase inhibitor (ARI) has beneficial effects on asymptomatic cardiac abnormalities in diabetic patients with neuropathy. RESEARCH DESIGN AND METHODS: Diabetic subjects with neuropathy (n = 81) with either a low diastolic peak filling rate or impaired augmentation of left ventricular (LV) ejection fraction (LVEF) during maximal bicycle exercise were identified by gated radionuclide ventriculography. Coronary artery disease, left ventricular hypertrophy, and valvular heart disease were excluded by clinical evaluation, myocardial perfusion imaging, and echocardiography. Subjects were randomized to receive blinded treatment with either the placebo or the ARI zopolrestat 500 or 1,000 mg daily for 1 year. RESULTS: After 1 year of ARI treatment, there were increases in resting LVEF (P < 0.02), cardiac output (P < 0.03), LV stroke volume (P < 0.004), and exercise LVEF (P < 0.001). In placebo-treated subjects, there were decreases in exercise cardiac output (P < 0.03), stroke volume (P < 0.02), and end diastolic volume (P < 0.04). Exercise LVEF increased with ARI treatment independent of blood pressure, insulin use, or the presence of baseline abnormal heart rate variability. There was no change in resting diastolic filling rates in either group. CONCLUSIONS: Diabetic patients with neuropathy have LV abnormalities that can be stabilized and partially reversed by ARI treatment.     

超声心动图评价起搏模式及起搏部位对心脏再同步化治疗效果的影响

目的：评价超声心动图在心力衰竭患者心脏再同步化治疗（cardiac resynchronizatio therapy，CRT）中的应用价值，探讨起搏模式及起搏部位对其产生的影响。方法：34例患者植入双室起搏器后随机进行4种不同模式起搏（双腔起搏，左室起搏，右室起搏和不起搏即窦性心律状态）。行常规超声心动图及二维彩色组织多普勒（Doppler tissue imaging，DTI）检查，测量左室射血分数（LVEF）、每搏输出量（Sv）、节段心肌作功指数（MPIr）和每个节段心电图QRS波起始至该节段收缩达峰时间（Ts），并比较左室电极放置在不同位置对心功能的影响。结果：左室起搏和双腔起搏提高SV（均P〈0．02）和LVEF（均P〈0.001）。左室起搏和双腔起搏下左室节段MPIr改善（均P〈0．0001），下壁和前壁基底段Ts差缩短（均P〈0．0001）。电极放置在心脏侧后静脉或侧静脉时SV、LVEF和Ts较后静脉或前静脉明显改善。结论：左室起搏和双腔起搏可明显改善心力衰竭患者的心功能。超声心动图可以无创评价CRT治疗效果，并随访预后。     

Relative effects of fat-, carbohydrate- and protein-containing liquid diets on cardiac output in healthy adult subjects.

1. Nine healthy adult subjects consumed four types of proprietary liquid diet of similar volume and calorific value but of different nutritional composition. The effects on resting cardiac output, mean blood pressure and pulse rate were measured. 2. A significant rise in cardiac output occurred with the balanced, protein and carbohydrate diets but not with the fat diet. The greatest rise was seen with the balanced diet. Water alone had no effect on cardiac output. 3. The average time taken to reach peak cardiac output was shortest with the carbohydrate diet and longest with the fat diet. 4. The increases in cardiac output resulted from a rise in both pulse rate and stroke volume. The carbohydrate diet produced the most sustained rise in pulse rate but the least sustained elevation in stroke volume. 5. No significant changes were seen in mean blood pressure when each liquid meal was compared with water. 6. Our data show that the increase in cardiac output with liquid ingestion is related to the dietary components. These effects are additive.     

Hemodynamic effects of pyruvate infusion in dogs

Although pyruvate supplementation enhances endurance in humans and increases cardiac output in dogs, its effects on cardiac and peripheral vascular function are not known. Thus, we assessed the cardiovascular effects of pyruvate infusion.

Aortic, left ventricular (LV), and pulmonary (Ppa) pressures and LV stroke volume (Sv_lv; derived from aortic flow probe) were measured after thoracotomy in eight anesthetized dogs. LV area or volume changes were measured using either an epicardial echocardiography (n = 6) or a conductance catheter (n = 2). LV end-systolic elastance (Ees_lv) and preload recruitable stroke force (PRSF_lv) relations, as estimates of contractility, were generated by transient inferior vena cave occlusion. Simultaneous stroke volume to arterial pressure relations during the occlusions were used to measure arterial elastance (Ea), and steady-state systemic and pulmonary vascular resistances were used as measures of arterial tone. Graded doses of pyruvate (8, 16, and 32 mg/kg/min), dobutamine (positive control) and propranolol (negative control) and placebo (volume control) were sequentially given.

Dobutamine increased Ees_lv PRSF_lv, whereas propranolol had the opposite effect on Ees_lv and PRSF_lv. Pyruvate at 32 mg/kg/min increased heart rate, Ppa, and SV_lv and decreased LV end-diastolic area, and systemic vascular resistance without changing arterial pressure, Ees_lv PRSF_lv. or Ea.

We conclude that pyruvate infusion in normal dogs induces venodilation but does not alter either cardiac contractility or arterial tone.     

Optimization of Ventricular Function by Improving the Activation Sequence During Ventricular Pacing

Abnormal electrical activation occurring during ventricular pacing reduces left ventricular (LV) pump function. Two strategies were compared to optimize LV function using ventricular pacing, minimal asynchrony and optimal sequence of electrical activation. ECG and hemodynamics aortic flowpmbe, thermodilution cardiac output, LV pressure and its maximal rates of rise (LVdP/dtpos) and fall (LVdP/dtneg) were measured in anesthetized open-chest dogs (n = 7) with healthy hearts. The QRS duration (a measure of asynchrony of activation) was 47 ± 5 ms during sinus rhythm and increased to 110 ± 12 ms during DDD pacing at the right ventricular (RV) apex with a short AV interval. During pacing at the LV apex and LV base, the QRS duration was 8%± 7% and 15%± 7% (P < 0.05) longer than during RV apex pacing, respectively. Stroke volumes, LVdP/dtpos and LVdP/dtneg, however, were higher during LV apex(15%± 16%, 10%± 12% [P<0.05], and 15%± 10%, respectively) and LV base pacing (11%± 12% [P<0.05], 3%± 12%, and 3%± 11%, respectively) than during RV apex pacing. Systolic LV pressure was not influenced significantly by the site of pacing. Biventricular pacing (RV apex together with one or two LV sites) decreased the QRS duration by approximately 20% as compared with RV apex pacing, however, it did not improve stroke volumes, LVdP/dtpos and LVdP/dtneg beyond those during pacing at the LV apex alone. In conclusion, the sequence of electrical activation is a stronger determinant of ventricular function than the synchrony of activation. For optimal LV function the selection of an optimal single pacing site, like the LV apex, is more important than pacing from multiple sites.     

Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure.

We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.     

The calcium carbimide-ethanol interaction: effects of ethanol dose.

In a double-blind, placebo-controlled study involving five male alcoholic volunteers, oral administration of 0.7 mg/kg of calcium carbimide (CC) 12 hr before ingestion of ethanol (0.125, 0.25, and 0.5 gm/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia, and decreased diastolic blood pressure. The order of intensity of the interaction with regard to ethanol dose was 0.5 greater than 0.25 greater than 0.125 k gm/kg. The subjects were aware of a CC-ethanol interaction only for 0.25 and 0.5 gm/kg of ethanol, for which heart rate was elevated above 100 bpm. With the criterion of heart rate above 100 as indicative of the CC-ethanol interaction, the onset was 0.25 and 0.38 hr for the 0.5 and 0.25 gm/kg ethanol doses and the duration of the interaction was 1.0 and 0.38 hr, respectively. There were positive linear correlations between blood acetaldehyde level and both heart rate and pulse pressure. There was appreciable individual variability in the intensity and duration of the interaction. Pretreatment with CC reduced the rate of ethanol metabolism at the 0.5 gm/kg ethanol dose.     

Contribution of Atrioventricular Synchrony to Left Ventricular Systolic Function in a Closed-Chest Canine Model of Complete Heart Block: Implications for Single-Chamber Rate-Variable Cardiac Pacing

This study assessed the impact of atrioventricular (AV) synchrony on characteristics of left ventricular (LV) systolic function during ventricular pacing over a wide heart rate range in a conscious closed-chest canine model of complete AV block. Ten healthy adult dogs underwent thoracotomy during which complete AV block was created by formaldehyde injection, and paired ultrasonic sonomicrometers were positioned on the LV anterior-posterior minor axis. Following recovery from surgery, peak and end-diastolic LV transmural pressure, maximum dP/dt, stroke work, end-diastolic minor axis dimension, and maximum velocity of shortening, were quantitated at heart rates of 80, 100, 120, 140, and 160 beats per minute (bpm) during both ventricular pacing alone and AV sequential pacing with increasing AV intervals (0, 50, 100, 150, 200, 250, and 300 ms). Over the heart rate range tested, parameters of LV systolic function did not differ significantly during ventricular pacing with or without AV synchrony. For example, during ventricular pacing alone maximum LV dP/dt varied from 2110 +/- 70 mmHg/s to 2463 +/- 567 mmHg/s, a range essentially identical to that observed in the presence of AV synchrony. On the other hand, although the impact on LV performance of varying AV interval from 0 to 300 ms was small, differences tended to become more pronounced at higher pacing rates. At 80 bpm, neither stroke work nor maximum LV dP/dt were affected by change in AV interval, while at heart rates greater than or equal to 120 bpm both stroke work and LV dP/dt tended to maximize at AV intervals of 50 and 100 ms and thereafter declined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man

Blockade of cardiac autonomic nervous activity by an intravenous injection of 0.2 mg/kg propranolol and 0.04 mg/kg atropine was used with cardiac catheterization to study intrinsic cardiac function in 47 patients with normal hearts and known graded myocardial disease. After blockade, significant hemodynamic abnormalities became apparent at rest in the majority of patients with known disease, many of whom had normal control findings. This occurred partly through a reduction in the normal range of cardiac function at rest, and partly through changes in the abnormalities associated with disease: after blockade, diseased hearts had normal stroke volumes, but beat more slowly, and had higher left ventricular filling pressures. The heart rate after blockade was fixed; this was defined as the intrinsic heart rate (IHR); it ranged from 57 to 126 beats/min in different patients. Both the IHR and left ventricular end-diastolic pressure after blockade were sensitively and quantitatively related to the severity of myocardial disease. When, after blockade, arterial pressure was raised by angiotensin, the IHR was unchanged; normal hearts maintained their stroke volume and increased stroke work; diseased hearts maintained stroke volume less well and stroke work was unchanged or fell. Abnormal ventricular responses corresponded well with abnormal ventricular function at rest.In different patients the IHR was significantly related to each available index of left ventricular function. Other studies in animals have shown that the IHR is closely related to intrinsic myocardial contractility in certain forms of experimental heart failure. An analogous relationship existing between the IHR and myocardial function in patients with heart disease is suggested as the explanation for the IHR/ventricular function relationship in this study. If so, the IHR may prove valuable as an index of myocardial function in man, since it can be measured simply and safely in clinical practice.     

Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice

Mice lacking natriuretic peptide receptor A (NPRA) have marked cardiac hypertrophy and chamber dilatation disproportionate to their increased blood pressure (BP), suggesting, in support of previous in vitro data, that the NPRA system moderates the cardiac response to hypertrophic stimuli. Here, we have followed the changes in cardiac function in response to altered mechanical load on the heart of NPRA-null mice (Npr1-/-). Chronic treatment with either enalapril, furosemide, hydralazine, or losartan were all effective in reducing and maintaining BP at normal levels without affecting heart weight/body weight. In the reverse direction, we used transverse aortic constriction (TAC) to induce pressure overload. In the Npr1-/- mice, TAC resulted in a 15-fold increase in atrial natriuretic peptide (ANP) expression, a 55% increase in left ventricular weight/body weight (LV/BW), dilatation of the LV, and significant decline in cardiac function. In contrast, banded Npr1+/+ mice showed only a threefold increase in ANP expression, an 11% increase in LV/BW, a 0.2 mm decrease in LV end diastolic dimension, and no change in fractional shortening. The activation of mitogen-activated protein kinases that occurs in response to TAC did not differ in the Npr1+/+ and Npr1-/- mice. Taken together, these results suggest that the NPRA system has direct antihypertrophic actions in the heart, independent of its role in BP control.     

超声心动图在诊断酒精性心肌病中的应用价值

目的探讨超声心动图在诊断酒精性心肌病中的应用价值。方法应用彩色多普勒超声心动图检测32例长期大量饮酒所致酒精依赖患者静息状态下的心内结构、血流和功能,从心脏各房室内径、室壁厚度、室壁回声、各室壁运动幅度、室壁增厚率、左室射血分数、各瓣膜形态结构、血流及功能等指标进行多方面观察,结合病史做出超声提示。结果左室舒张末期内径不同程度增大者32例,左室舒张末内径增大并左房内径增大者24例,以左心室增大为主的全心增大者6例,左室壁对称性轻度肥厚者9例,左室心肌内出现散在斑点状中强回声17例,左室心内膜增厚,回声增强10例,左心功能减低者20例(62.5%),左心功能减低合并不同程度肺循环高压者4例,左心增大伴左室心尖部附壁血栓者1例。结论超声心动图在酒精性心肌病的诊断中具有重要的临床应用价值,是临床医师诊断酒精性心肌病的重要辅助检查手段。