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Curcumin ameliorates left ventricular function in rabbits with pressure overload: inhibition of the remodeling of the left ventricular collagen network associated with suppression of myocardial tumor necrosis factor-alpha and matrix metalloproteinase-2 expression.

OBJECTIVE: Curcumin is a wide-spectrum cellular protector with antiinflammatory, antioxidizant, and antifibrotic effects. This study was conducted to investigate its effects on myocardial collagen remodeling in pressure overloaded rabbits. METHODS AND RESULTS: Pressure overloaded rabbits were established by partial abdominal aorta ligation. The rabbits were divided into the sham-operation group, vehicle group and curcumin group. Curcumin was administered orally at a dose of 100 mg/kg.d in 10 ml of 2.5% polyethylene glycol solution and the other 2 groups were given the same dose of polyethylene glycol solution. Compared with the vehicle group, left ventricular function in the curcumin group was significantly ameliorated, as indicated by decreased left ventricular end-diastolic pressure, left ventricle weight to body weight ratio, and the left ventricular posterior wall thickness. The collagen volume fraction in the curcumin group was also reduced. Myocardial tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP)-2 expression were significantly overexpressed in the vehicle group and markedly suppressed in the curcumin group at both the 4th and 8th weeks. At the end of the 8th week, the ejection fraction in the curcumin group was increased compared with that in the vehicle group. CONCLUSION: Curcumin improved left ventricular function in pressure overloaded rabbits. This might be due to inhibition of collagen remodeling associated with suppression of myocardial expression of tumor necrosis factor-alpha, and matrix metalloproteinase-2.

Animals↗

[Digital subtraction angiography and Fourier analysis of the left ventriculography: new methods of analyzing left ventricular function].

To evaluate two new methods of analyzing left ventricular function, digital subtraction left ventriculography (DSLV) and Fourier analysis of left ventriculography (FALV) were performed after conventional left ventriculography (LV) in 17 consecutive catheterized cases. Ejection fraction of FALV and LV corresponded closely with the correlation coefficient of 0.906, while segmental wall motion corresponded less with the range of correlation coefficients from 0.56 for the apical segment to 0.94 for the anterior wall. In 10 cases with asynergic segments of the left ventricle, Fourier analysis showed less hypokinesis in four (all had hypokinesis at the septal segment), the same degree in five and more in one case, suggesting the possibility of FALV to evaluate three-dimensional left ventricular function in a single projection.

Angiography, Digital Subtraction↗

A two phase harmonic model for left ventricular function.

A minimal model for mechanical motion of the left ventricle is proposed. The model assumes the left ventricle to be a harmonic oscillator with two distinct phases, simulating the systolic and diastolic phases, at which both the amplitude and the elastic constant of the oscillator are different. Taking into account the pressure within the left ventricle, the model shows qualitative agreement with functional parameters of the left ventricle. The model allows for a natural explanation of heart failure with preserved systolic left ventricular function, also termed diastolic heart failure. Specifically, the rise in left ventricular filling pressures following increased left-ventricular wall stiffness is attributed to a mechanism aimed at preserving heart rate and cardiac output.

Biological Clocks↗

Left ventricular function following attempted surgical repair of tetralogy of Fallot.

Left ventricular function was assessed by angiographic methods in 40 patients (ages 3-27), 1-12 years following repair of tetralogy of Fallot. Twenty of the 40 patients (group A) had a satisfactory repair with a pulmonary-systemic flow ratio (Qp/Qs) less then or equal to 1.5 and a right ventricular systolic pressure of less than or equal to 60% of the left ventricular value. The other 20 patients (group B) had a Qp/Qs greater than 1.5 and/or a right ventricular systolic pressure greater than 60% of the left ventricular value. Group A patients had a normal left ventricular end-diastolic volume (LVEDV), end-diastolic pressure (LVEDP), ejection fraction (LVEF), and mass (LVM), while the group B patients had significantly elevated LVEDV, LVEDP, LVM, and a significantly depressed LVEF. These findings indicate that patients with a satisfactory hemodynamic repair of tetralogy of Fallot have normal left ventricular function while patients with postoperative unsatisfactory hemodynamics have significantly impaired left ventricular function.

Adolescent↗

Longitudinal left ventricular function in a population of healthy adults: a tissue Doppler imaging study.

BACKGROUND: Longitudinal left ventricular function is a major determinant of global ventricular function and is probably more sensitive than radial function in the detection of disease. Tissue Doppler imaging of the mitral annulus allows the study of longitudinal left ventricular function. METHODS: Forty-five healthy volunteers divided into two groups (younger and older than 45 years) were studied with pulsed tissue Doppler imaging of the 4 sides of the mitral annulus (septal, lateral, inferior, anterior) in 4 and 2 apical chamber views. In each wave (systolic-s, rapid filling-e, atrial contraction-a) we analyzed velocities, time intervals and velocity-time integrals, as well as heterogeneity and asynchrony indexes. Data were compared between the different sides in each group, between groups and with conventional Doppler data. RESULTS: In contrast to the septal side, the lateral side of the annulus shows higher velocities and velocity-time integrals of the s and e waves, with non-significantly shorter isovolumic relaxation time and shorter time to peak e. There is functional agreement between the lateral and inferior sides versus the septal and anterior sides of the annulus. Most systolic parameters remained unchanged with aging; however, aging was associated with decreased e velocity, increased a velocity and inverted e/a ratio. The relation between s and fractional shortening also did not change with aging. Annular isovolumic contraction time and isovolumic relaxation time were shorter than their respective global time intervals. CONCLUSIONS: This study shows that there are physiological differences in velocities, time intervals and velocity-time integrals between the 4 sides of the mitral annulus, reflecting physiological heterogeneity and asynchrony, and that some of these parameters are age dependent. These data also contribute to a better understanding of longitudinal left ventricular function and may be useful in future studies as reference values in control groups.

Adult↗

The effect of nifedipine on normal and ischemic left ventricular function during atrial pacing stress.

We studied 44 patients (group I: 9 with insignificant disease and group II: 35 with significant coronary artery disease) by nuclear angiography during the controlled increase in heart rate by atrial pacing to evaluate the effect of 20 mg of sublingual nifedipine on left ventricular function. Left ventricular volumes were calculated using count-derived changes: end-diastolic (EDE), end-systolic (ESE), stroke volume (SVE) and cardiac output equivalents (COE) and ejection fraction (EF) and ejection rate (ER) were calculated during basal sinus rhythm (C) and at the maximal atrial pacing (AP) rate with and without nifedipine. In normal subjects, AP decreased ventricular volumes. The administration of nifedipine decreased blood pressure but had no further effect on left ventricular volume. In the ischemic ventricle, AP produced reversible ventricular wall paresis with a smaller decrease in EDE, an increase in ESE and a significant fall in EF. Nifedipine induced a striking improvement in EF and ER. This was probably a consequence of afterload reduction and increased coronary blood flow.

Adult↗

A prospective study found impaired left ventricular function predicted job retirement after acute myocardial infarction.

OBJECTIVE: Impaired left ventricular function is associated with poor prognosis after acute myocardial infarction (MI). It might be hypothesized that impaired left ventricular function would also affect work outcome; however, no existing data address this hypothesis. This study examines whether reduced left ventricular systolic function had any influence on the 4-year retirement rate after acute MI. STUDY DESIGN AND SETTING: We conducted a prospective study including 242 working-active patients with MI. Left ventricular ejection fraction (LVEF) was estimated by echocardiography during hospital admission. Data about work outcome after 4 years were collected by telephone interviews. RESULTS: Fifty percent were retired by the end of follow-up. Moderately or severely reduced LVEF (35%) increased the risk of retirement almost twofold (risk ratio RR=1.8, 95% confidence interval CI=1.3-2.5). After adjusting for confounding factors, reduced LVEF was an independent predictor of retirement. Based on a stratified analysis, being female (RR=3.90, 95% CI=1.18-12.62) or having heavy physical job demands (RR=3.83, 95% CI=1.02-14.30) had a more pronounced impact on retirement for patients with LVEF 35%, compared with patients with better left ventricular function. CONCLUSION: We conclude that impaired left ventricular systolic function is a prognostic determinant of retirement from the job market after acute MI.

Adult↗

Combined effect of the force-frequency and length-tension mechanisms on left ventricular function in patients with dilated cardiomyopathy.

BACKGROUND: The myocardial length-tension and the force-frequency relations are important mechanisms that regulate the contractile strength of the heart. AIMS: To evaluate in humans the effect on left ventricular function of the interaction between the myocardial length-tension and force-frequency relations. METHODS AND RESULTS: Eight patients with dilated cardiomyopathy (DCM) and 6 control subjects underwent radionuclide monitoring of left ventricular function during atrial pacing, saline loading and atrial pacing at the end of saline loading. In controls, atrial pacing reduced left ventricular end-diastolic (P < 0.001) and end-systolic volumes (P < 0.001) with no change in ejection fraction whereas after volume expansion end-diastolic volume (P < 0.001) and ejection fraction (P < 0.001) increased. Atrial pacing after volume expansion increased ejection fraction (P < 0.05). In patients with DCM, ejection fraction was reduced during atrial pacing (P < 0.001) and volume expansion (P < 0.05) due to an increase in left ventricular end-systolic volume (P < 0.001). Pacing tachycardia after volume expansion further increased end-systolic volume and reduced ejection fraction with a significant 'pacing by load' interaction (P < 0.001). Peak filling rate increased at each step in controls while it remained unchanged in patients with DCM. CONCLUSION: The heart rate increase during left ventricular distension improves ventricular function in normals and has detrimental effects in patients with DCM.

Adult↗

[Coronary surgery in patients with severely impaired left ventricular function].

Views on surgical treatment of patients with coronary disease and severely restricted left ventricular function are still controversial. In the present work the authors compare the results of direct reconstruction of the coronary arteries in 184 patients with satisfactory or medium restricted left ventricular function (SLV) with a group of 77 patients with severely restricted left ventricular function (RLV). Twenty-three clinical, angiographic, peroperative and postoperative indicators were compared. Patients with RLV had more frequently a myocardial infarction before operation, on average a more restricted functional capacity and lower ejection fraction of the left ventricle than patients with SLV. The mortality during hospitalization was 1.1% in patients with SLV and 5.2% in patients with RLV. These results confirm that reconstruction of the coronary arteries is safe also in patients with a significantly restricted left ventricular function. An essential prerequisite of successful operation is perfect peroperative protection of the heart muscle by the method of continuous local cooling.

Coronary Disease↗

The effects of the pericardium on length-dependent regulation of left ventricular function in coronary artery surgery patients.

OBJECTIVE: To analyze the effects of the pericardium on the length-dependent regulation of myocardial function in coronary artery surgery patients. DESIGN: Prospective. SETTING: University hospital. PARTICIPANTS: Patients scheduled for elective coronary artery surgery. INTERVENTIONS: In 10 patients, a combined micromanometer transducer conductance catheter was inserted into the left ventricle for measurement of left ventricular pressures and volumes. MEASUREMENTS AND MAIN RESULTS: Consecutive data were obtained during a progressive increase in left ventricular pressures and volumes obtained by leg elevation in closed chest-closed pericardium and open chest-open pericardium conditions. Pericardiotomy did not alter baseline left ventricular hemodynamics. The effects of leg elevation were different, however. In closed chest-closed pericardium conditions, stroke volume and stroke work remained unchanged, whereas these parameters increased in open chest-open pericardium conditions. This increase was related to the increase in end-diastolic volume that was observed in open chest-open pericardium conditions and not in closed chest-closed pericardium conditions. CONCLUSIONS: In coronary artery surgery patients, pericardiotomy does not alter baseline left ventricular function. When cardiac load is increased by leg elevation, however, use of the Frank-Starling mechanism is enhanced in open chest-open pericardium conditions.

Coronary Vessels↗

Myocardial beta adrenoceptors and left ventricular function in hypertrophic cardiomyopathy.

OBJECTIVE: To assess the relation between left ventricular function and myocardial beta adrenoceptor density. METHODS: 17 patients with hypertrophic cardiomyopathy, six with and 11 without heart failure, were studied. Left ventricular function was assessed by echocardiography, and myocardial beta adrenoceptors by positron emission tomography. Patient data were compared with those obtained in normal controls. RESULTS: Myocardial beta adrenoceptor density in the 17 patients was 7.00 (SD 1.90) pmol/g v 11.50 (2.18) pmol/g in normal controls (P < 0.01). beta Adrenoceptor density in the six patients with left ventricular failure was 5.61 (0.88) pmol/g v 7.71 (1.86) pmol/g in the 11 patients with normal ventricular function (P < 0.05), and there was a significant correlation (r = 0.52; P < 0.05) between left ventricular fractional shortening and myocardial beta adrenoceptor density. A positive correlation (r = 0.51; P < 0.05) was also found between myocardial beta adrenoceptor density and the E/A transmitral flow ratio, an index of left ventricular diastolic function. CONCLUSIONS: There is myocardial beta adrenoceptor downregulation in patients with hypertrophic cardiomyopathy with or without signs of heart failure.

Adult↗

[Relationship between coronary flow reserve and recovery of regional left ventricular function in patients with tako-tsubo-like transient left ventricular dysfunction].

OBJECTIVES: This study assessed the relationship between coronary flow reserve and functional recovery of left ventricular wall motion in patients with tako-tsubo-like transient left ventricular dysfunction. METHODS: Coronary flow reserve was measured using the Doppler guide wire technique in the left descending coronary artery in nine consecutive patients (three men, six women, mean age 71 +/- 11 years) with tako-tsubo-like transient left ventricular dysfunction. Regional wall motion was analyzed to estimate anterior wall motion score index (anterior WMSI) by transthoracic echocardiography on admission and 3 weeks after the onset of symptoms. RESULTS: Anterior WMSI was 2.2 +/- 0.4 on admission and improved to 1.4 +/- 0.5 at 3 weeks later (p < 0.001). Coronary flow reserve on admission was not correlated to the anterior WMSI on admission (r = 0.19, p = 0.63). However, coronary flow reserve on admission was correlated to the improvement in anterior WMSI (r = 0.74, p = 0.02). CONCLUSIONS: Coronary microcirculation is damaged in acute phase of tako-tsubo-like transient left ventricular dysfunction. The severity of coronary microvascular dysfunction influences the degree of left ventricular wall motion recovery.

Aged↗

Left ventricular function in chronic obstructive pulmonary disease.

The presence or absence of left ventricular dysfunction in chronic obstructive pulmonary disease has been debated for decades. I have reviewed the following evidence pertaining to this topic: (1) left ventricular pathologic abnormalities; (2) the methods used to determine left ventricular performance; (3) specific abnormalities of left ventricular function as revealed by systolic time intervals, left ventricular end-diastolic pressure, ejection fraction, isovolumic indices, and left ventricular function curves; and (4) pertinent experimental data. The bulk of the evidence indicates that the clinical symtoms of left-sided failure are unreliable in those with obstructive disease of the airways and that the great majority of patients have normal left ventricular function, once other causes are excluded. A small group of patients have some abnormalities in left ventricular performance, but these have not been clinically significant. The ultimate importance of such abnormalities awaits future investigation.

Animals↗

Use of peak systolic strain as an index of regional left ventricular function: comparison with tissue Doppler velocity during dobutamine stress and myocardial ischemia.

OBJECTIVES: The goals of this study were to examine peak systolic strain as an index of regional function in an animal model of inotropic stress and ischemia, and to compare these results with peak systolic myocardial tissue Doppler velocity (MDV). BACKGROUND: Myocardial tissue Doppler velocity is an objective measure of regional left ventricular responses to inotropic stimulation and ischemia, but it is affected by tethering from adjacent segments and translational movement. Myocardial Doppler strain (epsilon, relative change in length) is a more local measure of contractility, which can now be derived noninvasively from MDV. METHODS: Eight dogs underwent graded dobutamine infusion followed by coronary occlusion. Epicardial 2-dimensional echocardiography and color MDV of the left ventricle were obtained and digitized from the short-axis view at baseline and with dobutamine doses of 2, 4, and 8 microg/kg per minute. These were repeated 0, 10, 20, 45, and 90 seconds after occlusion of the left anterior descending artery (LAD) (n = 3) or circumflex coronary artery (n = 5). Dobutamine was continued at 8 microg/kg per minute during coronary occlusion. The peak systolic radial MDV (cm/s) and systolic strain (epsilon(s), percent thickening) in the anterior and posterior walls were measured off-line at each stage. RESULTS: Dobutamine caused an increase in MDV (P =.0001) and epsilon(s) (P =.09) above baseline values. Coronary occlusion caused a reduction in wall motion; after 45 seconds, all nonperfused segments were hypokinetic. There was a corresponding decrease in MDV and epsilon(s), but this occurred earlier for epsilon(s), and the difference between ischemic and nonischemic segments was greater for epsilon(s) than for MDV (P <. 03). Nonischemic regions trended to an increase in epsilon(s) (compensatory hyperkinesis), whereas MDV trended downward, probably reflecting the global decrease in left ventricular function. CONCLUSION: Both MDV and epsilon(s) increase with dobutamine and decrease during ischemia. epsilon(s) appears to respond to local ischemia earlier than MDV, perhaps because it is a more local measure. Thus epsilon(s) may prove to be an accurate parameter for the clinical recognition of regional ischemia.

Animals↗

Left ventricular function after valve repair for chronic mitral regurgitation: predictive value of preoperative assessment of contractile reserve by exercise echocardiography.

OBJECTIVES: We evaluated the value of preoperative assessment of left ventricular contractile reserve in predicting ventricular function after valve repair for minimally symptomatic mitral regurgitation. BACKGROUND: The optimal timing for operation in minimally symptomatic patients with significant mitral regurgitation is controversial. Accurate preoperative assessment of left ventricular function is difficult, and the ability to predict postoperative function is limited. Previous studies in patients undergoing mitral valve replacement may not be applicable in the present era of valve repair. METHODS: We performed exercise echocardiography in 139 patients with isolated mitral regurgitation and no coronary disease, 74 of whom subsequently underwent uncomplicated valve repair. We measured rest left ventricular end-systolic dimension, end-systolic wall stress and positive first derivative of left ventricular pressure (dP/dt). End-diastolic and end-systolic volumes and ejection fraction were measured preoperatively at rest, immediately after exercise and postoperatively. RESULTS: Ejection fraction decreased postoperatively to 55 +/- 10% from a rest preoperative value of 64 +/- 9% (p < 0.001). Compared with patients with a postoperative ejection fraction > or = (n = 56), patients with postoperative ejection fraction < 50% (n = 18) had a significantly lower preoperative exercise ejection fraction (57 +/- 11% vs. 73 +/- 9%, p < 0.0005), a larger exercise end-systolic volume index (32 +/- 8 vs. 18 +/- 7 cm3/m2, p < 0.0005) and a lower change in ejection fraction with exercise (-4 +/- 8% vs. 9 +/- 10%, p < 0.005). Preoperative rest indexes, including dP/dt, end-systolic wall stress and end-systolic volume index were less predictive, whereas exercise capacity, rest ejection fraction and end-systolic dimension were not predictive of post-repair ejection fraction. An exercise end-systolic volume index > 25 cm3/m2 was the best predictor of postoperative dysfunction, with a sensitivity and specificity of 83%. CONCLUSIONS: In minimally symptomatic patients with mitral regurgitation, latent ventricular dysfunction may be indicated by a limited contractile reserve, manifest at exercise as an inadequate increase in ejection fraction and a larger end-systolic volume. These variables may also be used to predict left ventricular function after repair.

Aged↗

Left ventricular function in endurance runners during exercise.

Left ventricular function in elite runners and controls was compared by means of nuclear angiocardiography. Fifteen middle- or long-distance runners and a control group of 10 sedentary to moderately physically active subjects were studied at rest and during semi-sitting incremental exercise. Ejection fraction was higher in the runners than the controls both at rest and during exercise. At the transition from rest to exercise left ventricular end-diastolic volume initially increased similarly in runners and controls by an average of 14 and 12%, respectively, with an increase in stroke volume by approximately 25 and 23%. The parallel increase in stroke volume and left ventricular end-diastolic volume could at least partly be because of the Frank-Starling mechanism. With increasing workloads, left ventricular end-diastolic volume and ejection fraction remained fairly constant, resulting in an unchanged stroke volume from the lowest to the highest exercise intensity. This was in the runners accomplished by a 41% increase in peak filling rate and a 38% increase in peak emptying rate with similar changes observed in the controls. This has to be due to increased myocardial contractility paralleling the systolic shortening with increasing heart rate. We conclude that endurance-trained athletes have a better systolic function expressed as higher ejection fraction both at rest and during exercise than untrained subjects reflecting an enhanced myocardial contractility contributing to the maintenance of a large stroke volume during exercise. The regulatory mechanisms however, appear to be similar for athletes and healthy controls.

Adult↗

Left ventricular function in acute and chronic coronary artery disease.

The evaluation of left ventricular function in patients with acute myocardial infarction has shown: 1. Limitations in the use and interpretation of central venous pressure. 2. Pulmonary artery end-diastolic pressure reflects left ventricular end-diastolic pressure in the absence of pulmonary vascular or mitral valve disease. 3. Frequent elevations of left ventricular filling pressure in mild or clinically uncomplicated infarction. 4. Anterior infarctions present greater depression of left ventricular function than inferior infarctions. 5. Initial hemodynamic measurements in cardiogenic shock can predict prognosis with medical management. 6. Left ventricular function frequently improves during the early convalescent period. 7. Hemodynamic monitoring can be useful in following changes in left ventricular function and the response to therapy. The assessment of left ventricular performance in patients with chronic heart disease has shown: 1. Resting hemodynamic measurements are often normal but abnormalities can be observed in patients with disease of the left anterior descending coronary artery, diffuse coronary involvement, and after myocardial infarction. 2. Increases in end-diastolic volume or dilatation and left ventricular mass or hypertrophy can develop in severe coronary disease and after myocardial infarction. 3. The size of abnormally contracting segment after myocardial infarction is related to abnormalities in compliance, ventricular end-diastolic pressure, end-diastolic volume, and clinical manifestations of heart failure. 4. Exercise and atrial pacing can produce clinical and hemodynamic abnormalities. 5. The ejection fraction is significantly related to the slope of the ventricular function curve. 6. Angiographic abnormalities of left ventricular wall motion can be increased with atrial pacing and reduced with nitroglycerin or epinephrine.

Acute Disease↗

Left ventricular function and oesophageal function in patients with angina pectoris and normal coronary angiograms.

Left ventricular function and oesophageal function (including oesophageal manometry and pH monitoring) were investigated and a psychiatric assessment carried out in 63 patients with angina pectoris and normal coronary angiograms. Twenty two (35%) patients had regional abnormalities of left ventricular wall motion (group A). Thirty six (57%) patients had an oesophageal abnormality (group B); 19 patients had gastro-oesophageal reflux and abnormal oesophageal motility, five had gastro-oesophageal reflux alone, and 12 had abnormal oesophageal motility alone. Only four had regional abnormalities of the left ventricular wall and abnormal oesophageal function. In nine (14%) patients left ventricular and oesophageal function were normal (group C). Psychiatric morbidity was significantly less common in group A than in groups B and C and was similar in group B and group C. A definite abnormality of left ventricular function, oesophageal function, or psychiatric morbidity is present in a high proportion of patients with angina pectoris and normal coronary angiograms and in some instances this may lead to specific treatment. If quantitative assessment of left ventricular function is normal, oesophageal investigations should be performed. Endoscopy of the upper gastrointestinal tract may demonstrate oesophageal disease, but, if findings are normal, oesophageal manometry and ambulatory oesophageal pH monitoring (including during treadmill exercise testing) should be carried out.

Adult↗