Circumferential Fiber Research Articles

Effect of selenium deficiency on cardiac function of individuals with severe disabilities under long-term tube feeding.

Eleven orally fed (group A) and 14 tube-fed patients (group B) with severe disabilities and neurological disorders were compared to determine whether selenium (Se) deficiency is present in patients undergoing long-term tube feeding, and to examine if Se supplementation has beneficial effects on their cardiac function. Assessments of Se intake, serum levels of Se, and cardiac-function analysis including chest X-ray, electrocardiography (ECG), and M-mode echocardiography (UCG) were made. For group B, the effect of Se supplementation on cardiac function was assessed. Statistical significance was determined using Mann-Whitney U test and Wilcoxon signed-rank test. Deficiencies of Se were found in group B. ECG abnormalities were more common in group B than group A. UCG showed a lower ejection fraction, a lower mean rate of circumferential fiber shortening corrected by heart rate, and a lower diastolic velocity of the left-ventricular posterior walls in group B than in group A. In group B, Se supplementation resulted in normalized serum Se levels, partial improvement of ECG abnormalities, and an increase of cardiac functions on UCG. It is thought that Se has beneficial effects on the myocardium of chronically tube-fed patients. Se supplementation is recommended in this population.

Measurement of myocardial contractility following successful resuscitation: quantitated left ventricular systolic function utilising non-invasive wall stress analysis

After successful resuscitation from cardiac arrest, prolonged contractile failure has been demonstrated in animal experiments. No systematic evaluation of myocardial contractility following successful resuscitation after human cardiac arrest exists. The aim of this study was to assess left ventricular contractility following human cardiac arrest with successful resuscitation. In 20 adult patients after cardiac arrest and in four control patients, the relation between meridional wall stress (MWS) and rate-corrected mean velocity of circumferential fibre shortening (Vcf c), a load independent and rate corrected index of left ventricular contractility was measured within 4 h after return of spontaneous circulation and after 24 h by means of transoesophageal echocardiography. As the normal values of Vcf c depend on MWS, a normal deviate (z) was calculated. A normal z-score is defined as 0±2, <−2 indicates reduced contractility, >+2 increased contractility. Data are presented as median and the interquartile range (IQR). For the comparison of related samples the Wilcoxon sign test was used. In most patients after cardiac arrest contractility was severely impaired within 4 h after successful resuscitation [z−7.0 (IQR −8.9–−2.5)]. Contractility did not significantly improve within the observational period [z after 24 h −3.7 (IQR −7.9–−1.8)] ( P=0.3). The four control patients had normal left ventricular contractility on arrival (z 0.0, range −0.9–0.8) and after 24 h (z 0.7, range −1.5–2.7). In conclusion non-invasive wall stress analysis can be applied to quantitate systolic left ventricular function, which was severely compromised in most patients within the first 24 h after successful resuscitation. Whether depression of left ventricular function is caused by cardiac arrest itself or by the underlying disease remains speculative.

Changes in left ventricular contractility with the phase of respiration

The end-systolic wall stress ( σ es)–velocity of circumferential fiber shortening ( V cfsc) relation was defined during the respiratory cycle, in order to obtain a totally noninvasive measure of left ventricular contractility. Eight young, healthy subjects were studied with echocardiography and calibrated carotid pulse tracings, while performing slow paced breathing. Left ventricular σ es vs. V cfsc relation was determined by fitting linear regression line to data points obtained at different times during the respiratory cycle. Data are given as mean±1SD. Left ventricular σ es and V cfsc exhibited small but significant changes during the respiratory cycle: σ es was highest in late inspiration (56.9±4.8 g/cm 2) and lowest in late expiration (49.2±3.7 g/cm 2); inversely, V cfsc was lowest during late inspiration (1.18±0.17 circ/s) and highest during late expiration (1.34±0.20 circ/s). The relation was significant in each subject ( r=−0.64±0.13) and remained inverse and significant, when it was determined separately for inspiration and expiration ( r=−0.61±0.17 and −0.68±0.12, respectively). At identical end-systolic wall stress, the velocity of shortening was greater during inspiration then expiration, suggesting that contractility was reduced during the expiratory phase. The reduced expiratory contractility might reflect increased vagal influence on the ventricular myocardium.

Age-related variation in left ventricular myocardial contractile state expressed by the stress velocity relation.

The assessment of ventricular function plays an important role in the pre- and postoperative management of many congenital heart abnormalities. Normal ranges in left ventricular systolic function indices have been defined during childhood and age-related alterations in left ventricular myocardial contractile state have recently been reported. This study was carried out to investigate the developmental changes in left ventricular contractile state expressed by the endsystolic meridional stress (ESS)/rate-corrected velocity of circumferential fiber shortening (VCFc) relation, calculated by echo in normal children and young adults. We examined 146 healthy subjects (80 males and 66 females), mean age 70.85 +/- 63.89 months (range 0.5-228) and body surface area (BSA) 0.807 +/- 0. 47 (range 0.18-2.01) with no clinical and echocardiographic evidence of cardiac disease and with normal blood pressure. The subjects were divided into three groups according to age: <6 months (group 1, n = 32), 6-36 months (group 2, n = 34), and >36 months (group 3, n = 80). Enddiastolic volume and mass (M) of the left ventricle were measured by M-mode Echo. ESS was considered as an index of afterload and the VCFc as an index of systolic ventricular function. The left ventricular ejection time used for the calculation of VCFc was measured from aortic flow obtained by PW-Doppler. The ESS/VCFc relation was used to assess left ventricular contractility. Systolic blood pressure, volume, and mass of the left ventricle increase with age. The gradual increase in pressure despite a stable mass/volume ratio [M/V = 0.900 + (0.0007 x age); r = 0.27, p < 0.005] resulted in a substantial increase of afterload [ESS = 29.78 + (0.116 x age); r = 0.58, p < 0.0001]. VCFc showed an inverse hyperbolic regression with afterload [VCFc = 1.01 + (7.598/ESS); r = 0.59, p < 0.0001]. The regression lines (best linear fit) between VCFc and ESS are significantly different in the three groups. The Y intercept was higher and the slope steeper in group 1 [VCFc = 1.74 - (0.017 x ESS); r = 0.65, p < 0.0005] vs group 2 [VCFc = 1.54 - (0.008 x ESS); r = 0.58, p < 0.001] and group 3 [VCFc = 1.52 - (0.007 x ESS); r = 0.57, p < 0.0001]. These data indicate that, in children, the volume and mass of the left ventricle increase, whereas the M/V ratio remains relatively constant; the progressive increase in arterial blood pressure explains the increase of afterload. The VCFc is higher in the first few years of life compared to that seen in older children due to reduced afterload and increased contractile state. Left ventricular contractility, expressed as ESS/VCFc relation, is thus inversely proportional to age. In the first months of life the left ventricular myocardium exhibits a higher basal contractile state and a greater sensitivity to changes in afterload. For obtaining an accurate assessment of left ventricular function, the ESS/VCFc relation in different age groups should be measured.

Comparative Hemodynamic Depression of Sevoflurane Versus Halothane in Infants

WODEY, ERIC; PLADYS, PATRICK; COPIN, CATHERINE; LUCAS, MARIE MADELEINE; CHAUMONT, ANDRA; CARRE, PHILIPPE; LELONG, BERNARD; AZZIS, OLIVIER; ECOFFEY, CLAUDE Author Information

Influence of age and low afterload on the stress-velocity relation of the left ventricle.

The relation between systolic meridional wall stress (WS) and velocity of circumferential fiber shortening (VcFc) is widely accepted as a preload-independent index of contractility, with a linear relation in most subjects older than 2 y. However, this relation seems to become different in infants and after administration of inotropic agents. We decided to study the nature of the stress-velocity relation by a cross-sectional assessment of the influence of age, low afterload, and increased contractility. Study subjects were 30 healthy infants, 32 healthy older children, and 35 asymptomatic older children after completion of anthracycline chemotherapy. WS and VcFc at rest were studied in these infants and children. WS and VcFc were also studied after dobutamine infusion in both groups of older children. Linear regression analysis of the stress-velocity relation showed parallel slopes between the older children at rest and the post anthracycline children after dobutamine. The regression lines between the infants at rest and the healthy older children after dobutamine were also parallel, but with a different and steeper slope compared with the former groups. When comparing the stress-velocity relation of the overall population at rest with the overall population after dobutamine, the resulting regression lines are curvilinear and parallel, with a steeper slope at low afterload. The stress-velocity relation in infants and after dobutamine, resulting in low afterload is different compared with the stress- velocity relation in older children at rest and at higher afterload. Data of the overall population at rest and after dobutamine suggest a curvilinear relation.

Postinfarction left-ventricular aneurysm: regional stress, function, and remodeling after aneurysmectomy.

Left-ventricular (LV) aneurysm formation after myocardial infarction (MI) leads to LV remodeling with global and regional cardiac dysfunction. LV aneurysmectomy (LVA) can often improve LV function, but changes of regional wall stress and systolic function in the noninfarcted segment before and after the operation remain poorly understood. The purpose of this study was to assess the effects of LVA on regional stress and systolic function in the noninfarcted region and to examine this procedure's impact on the LV remodeling in patients with LV aneurysm after myocardial infarction (MI). Using quantitative left ventriculography and pressure measurements, 11 patients with an anterior LV aneurysm were studied before and 8 months after standard linear repair (LVA group), and 10 patients with an anterior transmural infarction who received coronary artery bypass grafting were also studied (CABG group) in an attempt to separate the effects of aneurysmectomy from the effects of bypass surgery. Regional end-systolic (ESS) and end-diastolic (EDS) stresses of the contractile segment (CS) were computed by Janz's method. The total ejection fraction (EF) increased (p < 0.01) in the LVA group, whereas it did not change in the CABG group at 8 months after surgery. Both the end-diastolic and end-systolic volume indices of CS decreased (p < 0.01 and p < 0.01, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The mean velocity of circumferential fiber shortening (mean Vcf) of CS increased substantially (p < 0.01) in the LVA group and, less significantly (p < 0.05), in the CABG group. Regional ESS and EDS decreased (p < 0.01 and p < 0.05, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The increase in mean Vcf correlated strongly with the magnitude of decrease in ESS (r = -0.63, p < 0.01) in the LVA group but not in the CABG group. LVA can reduce regional afterload and improve ejection performance of the noninfarcted myocardium in many patients with a large anterior LV aneurysm and, moreover, may favorably affect the LV remodeling process after MI.

Effect of doubutamine-induced mild work load on high-energy phosphate metabolism in myopathic myocardium

In general, caridiac work load is not recommended in patients with heart failure, but they often experience mild work load in their daily life and it may have deleterious effect. We measured phosphocreatine (PCr) to beta-ATP ratio before and during 5mmg/kg/min infusion of dobutamine in 7 patients with dilated cardio myopathy (DCM) and in 8 normal subjects by MR-spectroscopy. Dobutarnine infusion was kept constant for 50 minutes. Myocardial contractility and ventricular size were determined by echocardiography with the same protocol. The ratio of myocardial PCr to ATP slightly increased from 1.7+/0.4 to 2.2 + /0 .6 in normal subjects but was unchanged from 1.5+/0.4 to 1.8+/-0.6 in patients with DCM. The heart rate and the mean rate of circumferential fiber shortening increased dose dependently both in patients with DCM and normal subjects. These results demonstrate that constant loading of dobutamine for hours had no deleterious effect on high energy phosphate metabolism in the myopathic myocardium. We concluded that the high-energy phosphate metabolism of stable cardiomyopathic patients is stable if the work load is temporary and weak. 206

Echocardiographic findings, 24-hour electrocardiographic Holter monitoring in patients with rheumatoid arthritis according to Steinbrocker's criteria, functional index, value of Waaler-Rose titre and duration of disease.

Electrocardiographic (ECG) and echocardiographic examinations and 24-h ECG Holter monitoring were carried out in 100 patients (age < 65 years) with rheumatoid arthritis (RA) of stages II-IV according to Steinbrocker's criteria. One hundred patients with osteoarthrosis, spondyloarthrosis and painful shoulder matched for age, sex and body surface area constituted the control group. All patients with myocardial infarction, hypertension, rheumatic fever or a history of diabetes were excluded. Cardiac involvement, evaluated by echo-Doppler cardiography, 24-h ECG Holter monitoring and an ECG at rest, occurred in 52 (52%) patients with RA and in 23 (23%) control group patients (p < 0.0005). In the RA group ECG examination, 1 mm ST depression in at least two consecutive leads was observed more frequently, and occurred statistically more frequently for the highest stage of RA according to Steinbrocker's criteria, highest level of functional index and longer duration of disease. The 24-h Holter ECG monitoring did not show any differences in frequency of rhythm disorders between the RA group and the control group. However, silent myocardial ischaemia episodes appeared more often in the RA group. An ECG examination revealed more cases of valvular heart disease, especially mitral insufficiency, in RA patients than in the control group. A mitral valve prolapse was noted in 6% of patients and a pericardial effusion in 4% of patients. Patients with RA were noted to have a larger diastolic left ventricular diameter and aortic root diameter, and smaller ejection fraction, mean velocity of circumferential fibre shortening and fractional shortening. The results of the examinations show that RA is associated with cardiac involvement in a significant proportion of cases.

Left ventricular mechanics after closure of ventricular septal defect: influence of size of the defect and age at surgical repair.

To evaluate the influence of the size of the defect and the age of surgical repair on left ventricular mechanics, including geometry, shape, diastolic and systolic function as well as myocardial contractility, we used cross-sectional echo-Doppler to study 20 patients (12 males, 8 females) who had undergone successful surgical closure of a ventricular septal defect. The patients were divided in two groups, corrected early and late, on the basis of the degree of left-to-right shunting (ratio of pulmonary to systemic output of greater or less than 2.5/1) and the age at the surgical repair (older or younger than 2 years of age). The group undergoing early correction included 11 patients, mean age 7.1+/-1.8 years (range 4.2-11.8 years), having surgery at mean age of 1.3+/-0.6 years for a large ventricular septal defect (mean ratio of pulmonary to systemic output of 3.1/1; range 3.4-2.7/1) with a mean postoperative follow-up 4.6+/-1.9 years. The group of nine patients undergoing late correction had a mean age of 11.3+/-4.9 years (range 6.7-17.2 years), with a later surgical repair (mean age 4.7+/-2.7 years) for a moderate-sized ventricular septal defect (mean pulmonary/systemic output ratio 2.1/1; range 2.3-1.7) and a mean postoperative follow-up of 7+/-4.2 years. Each group of surgically repaired patients was compared with a control group matched for age, body surface area and gender. No significant differences were found between the normal controls and those undergoing early correction for any assessed functional index regarding left ventricular geometry (normalized volumes and mass for body surface area, mass/volume and thickness/radius ratios), shape (long axis-short axis ratio), diastolic (mitral and pulmonary venous flow patterns) and systolic (fractional shortening and rate-corrected mean velocity of circumferential fibre shortening) function. In addition, the data points for each patient for the rate-corrected mean velocity of circumferential fibre shortening to end-systolic stress relationship were within the 95% confidence limits of normal, suggesting normal left ventricular contractility. On the other hand, the patients undergoing surgery at a later age showed a persistent increase of the normalized left ventricular end-diastolic volume and mass, with an higher mass/volume ratio and reduced end-systolic stress compared with normal controls. Furthermore, left ventricular shape (long axis-short axis ratio) was abnormal at end-diastole but with its normal values at end-systole. Our data suggest that, in the presence of a large ventricular septal defect, early successful surgical repair <2 years of age results in complete recovery of left ventricular mechanics in the postoperative follow-up. In contrast, surgical closure at > 2 years of age, even for a moderately sized ventricular septal defect, deleteriously affects postoperative left ventricular geometry and shape. Since prolonged volume overload may be detrimental to myocardial function, earlier surgical repair should be recommended.

Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice.

Heart failure is accompanied by severely impaired beta-adrenergic receptor (betaAR) function, which includes loss of betaAR density and functional uncoupling of remaining receptors. An important mechanism for the rapid desensitization of betaAR function is agonist-stimulated receptor phosphorylation by the betaAR kinase (betaARK1), an enzyme known to be elevated in failing human heart tissue. To investigate whether alterations in betaAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of betaARK1 or the beta2AR were mated into a genetic model of murine heart failure (MLP-/-). In vivo cardiac function was assessed by echocardiography and cardiac catheterization. Both MLP-/- and MLP-/-/beta2AR mice had enlarged left ventricular (LV) chambers with significantly reduced fractional shortening and mean velocity of circumferential fiber shortening. In contrast, MLP-/-/betaARKct mice had normal LV chamber size and function. Basal LV contractility in the MLP-/-/betaARKct mice, as measured by LV dP/dtmax, was increased significantly compared with the MLP-/- mice but less than controls. Importantly, heightened betaAR desensitization in the MLP-/- mice, measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol-stimulated membrane adenylyl cyclase activity), was completely reversed with overexpression of the betaARK1 inhibitor. We report here the striking finding that overexpression of this inhibitor prevents the development of cardiomyopathy in this murine model of heart failure. These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy.

Myocardial, erythropoietic, and metabolic adaptations to anemia of prematurity in infants with bronchopulmonary dysplasia

Objectives: The effects of anemia of prematurity during bronchopulmonary dysplasia (BPD) as well as on the metabolic and erythropoietic functions were determined before and after a transfusion. Fourteen anemic (Hb range: 65-88 gm/L), oxygen dependent (fraction of inspired oxygen ≤35%), nonventilated, preterm infants with BPD were studied at a postnatal age of 6 ± 2 weeks. Study Design: Cardiac output, heart rate, mean velocity of circumferential fiber shortening, shortening fraction (SF), and stroke volume were assessed by pulsed and continuous wave Doppler echocardiography. Values for resting oxygen consumption, carbon dioxide production, and energy expenditure were obtained by indirect calorimetry. The affinity of oxygenated hemoglobin was determined by a blood oxygen dissociation analyzer. Results: An increased hemoglobin level resulted in auppression of erythropoietin secretion ( p < 0.001), whereas heart rate, cardiac output, stroke volume, and SF decreased ( p < 0.05). Weight gain before and after transfusion were similar. Plasma lactate levels decreased from 1.6 ± 0.3 to 1.2 ± 0.3. Oxygen consumption, carbon dioxide production, and energy expenditure were not affected. Conclusions: Anemia of prematurity and BPD increase heart rate, cardiac output, stroke volume, and SF. These hemodynamic compensatory responses are normalized by transfusion. (J Pediatr 1998;132:630-4.)

Aging and Essential Hypertension: Effect of Left Ventricular Hypertrophy on Cardiac Function

This study was designed to analyze the cardiac effects of aging and of hypertension in patients with essential hypertension and with or without left ventricular hypertrophy (LVH). Thirty-one patients <55 years old and 66 patients >64 years old with essential hypertension were divided according to the presence or absence of LVH. Cardiac functional structure was assessed by 2D-guided M-mode echocardiography. The peak filling rate and the duration of rapid filling were obtained by digitizing septal and posterior wall echoes. In the older group only was systolic function significantly impaired in subjects with LVH when compared with subjects without LVH [velocity of circumferential fiber shortening (L/msec): 1.40 ± 0.24 v 1.18 ± 0.25; fractional fiber shortening (%): 43.06 ± 5.02 v 36.26 ± 7.1; ejection fraction (%): 81.1 ± 5.1 v 73.13 ± 9.2; P < .05]. Older patients, even without LVH, showed a longer duration of rapid filling (321.0 ± 108.3 msec) and lower peak filling rate (7.01 ± 1.86 cm/sec) in comparison with younger persons with or without LVH. In the older subjects the increase in left ventricular mass was associated with a decrease of velocity of circumferential fiber shortening (r = −0.48, P < .01), fractional fiber shortening (r = −0.40, P < .01), and ejection fraction = −0.50, P < .01), whereas there was no correlation in the younger group. The present findings of impaired diastolic filling even in the absence of LVH in the elderly, and the deterioration of systolic function parallel to the increase in LV mass suggest that aging is associated with a decrease in the number of functioning contractile elements per unit of cardiac mass.

Lack of beneficial effects of growth hormone treatment in conscious dogs during development of heart failure.

The effects of chronic treatment with growth hormone (porcine GH, 0.56 mg.kg-1.day-1 s.c.) were examined in dogs with heart failure induced by rapid ventricular pacing (240 beats/min) for 4 wk. Fourteen conscious dogs were studied 2-3 wk after surgical instrumentation with catheters in the descending aorta and left atrium, a pressure gauge in the left ventricle (LV), a flow probe around the ascending aorta, pacing leads on the ventricular free wall and left atrium, and ultrasonic crystals on the opposing anterior and posterior endomyocardium of the LV. GH treatment for 4 wk significantly increased both body weight and plasma insulin-like growth factor 1 (IGF-1) compared with vehicle-treated dogs (P < 0.01, +2.0 +/- 0.5 vs. +0.3 +/- 1.1 kg; 1,043 +/- 218 vs. 241 +/- 64 ng/ml, respectively). However, the changes in resting LV systolic (i.e., both isovolumic and ejection phases) and diastolic function (i.e., isovolumic relaxation time constant tau) and the systemic vascular resistance were similar for the GH- and vehicle-treated groups during the development of heart failure. LV contractile reserve, assessed with step infusion of isoproterenol or dobutamine challenge, was markedly attenuated after heart failure, but there were no differences between the GH- and vehicle-treated groups. During the progression of heart failure, the increases in plasma atrial natriuretic peptide correlated (P < 0.01) directly with left atrial pressure and inversely with LV circumferential fiber shortening. However, GH treatment did not substantially modify these relationships. In addition, renal function and myocardial ultrastructure at the advanced stage of heart failure also showed similar changes for the GH- and vehicle-treated groups. We conclude that in conscious dogs during the development of congestive heart failure produced by rapid ventricular pacing, GH at a dose that increases body weight and plasma IGF-1 levels does not affect LV performance or systemic vascular dynamics.

Acute Changes in Preload, Afterload, and Systolic Function After Superior Cavopulmonary Connection

Background. Superior cavopulmonary connection reduces the volume work of the single ventricle. Methods. To determine the effects of superior cavopulmonary connection on preload, wall stress (or afterload), and systolic ventricular function, we studied 9 patients before and after operation, and at hospital discharge. Using echocardiography, preload was estimated by the ventricular end-diastolic area, and wall stress was calculated at end-systole and peak-systole. Ventricular function was represented by rate-corrected velocity of circumferential fiber shortening and fractional area change divided by rate-corrected ejection time. Results. End-diastolic area and wall stress decreased postoperatively. Ventricular wall thickness increased with a concomitant decrease in cavity area. There was no change in mean blood pressure or heart rate or in rate-corrected velocity of circumferential fiber shortening or fractional area change divided by rate-corrected ejection time. These findings persisted at hospital discharge. Conclusions. In single ventricles, superior cavopulmonary correction results in an immediate decrease in preload and afterload. The decrease in afterload results primarily from alterations in ventricular geometry. Although no improvement in systolic function was noted, diminished work related to the reduction in loading conditions may have beneficial long-term effects on preserving myocardial performance.

Assessment of a new ventricular contractile index obtained with transoesophageal echocardiography before and after cardiopulmonary bypass in cardiac surgical patients

We have compared a new contractile index "left ventricular end-systolic wall stress-heart rate-corrected velocity of circumferential fibre shortening (vcfc)" with conventional contractile indices in 13 patients undergoing coronary artery bypass grafting. We generated the slopes of the "end-systolic wall stress-vcfc", "end-systolic wall stress-area" and "peak arterial pressure-area" relationships by altering arterial pressure before and after cardiopulmonary bypass (CPB). In all patients, significant correlations were obtained for end-systolic wall stress-area and peak arterial pressure-area relationships before and after CPB. In all patients, significant inverse linear correlations were obtained for the end-systolic wall stress-vcfc relationship before CPB; however, inverse linear correlation was absent in eight patients after CPB. It may be that the increased afterload had less influence on left ventricular systolic function after CPB as a possible mechanism of loss of the inverse linear correlation in the end-systolic wall stress-vcfc relationship.

Left ventricular mechanics and geometry in patients with congenital complete atrioventricular block.

Radiographic evidence of cardiomegaly is common in patients with congenital complete atrioventricular block (CCAVB). It has been speculated that left ventricular (LV) remodeling and increased stroke volume counteract the bradycardia, but the effects of slow heart rate and atrioventricular asynchrony on LV dimensions, geometry, wall stress, and function have not been examined in detail. Thirty patients with CCAVB without associated congenital heart disease (mean age, 8.5+/-5.3 years; range, 0.2 to 20 years) were included in a cross-sectional two-institution study. Thirty-five echocardiograms were performed using standard techniques. ECG and 24-hour ECG recordings were reviewed. Seven patients did not receive a pacemaker, whereas 23 patients underwent pacemaker implantation after the echocardiogram. Compared with normal control subjects, LV volume (Z score=1.5+/-1.3) and LV mass (Z=1.2+/-1.5) were significantly increased, whereas LV mass-to-volume ratio (1.1+/-0.3) and geometry (short-axis diameter/length ratio=0.65+/-0.09) were normal. LV end-systolic stress (ESS) (a measure of afterload) was normal (Z score=0.2+/-2.3), whereas shortening fraction (Z=3+/-2.9) and velocity of circumferential fiber shortening (VCF) (Z=3+/-3.1) were increased. The relationship between VCF and ESS (a preload-insensitive and afterload-adjusted index of contractility) was increased (Z=2.2+/-2) with only small increase in preload (Z=1.02+/-1.1). Regression analyses showed no significant change over age in LV mass, volume, geometry, loading conditions, or systolic function. Patients who ultimately met criteria for pacemaker implantation did not differ from those who did not in terms of heart rate or LV function but did have increased LV volume (Z score=1.8+/-1.4 versus 0.4+/-0.9, P=.03) and LV mass (Z score=1.7+/-1.2 versus 0.2+/-1.7, P=.001) compared to the unpaced group. In most patients with CCAVB, the LV was enlarged with normal geometry and enhanced systolic function during the first two decades of life. The degree of LV dilation and enhanced function did not significantly change with age. In patients who ultimately underwent pacemaker implantation LV function did not differ from those who remained unpaced, but evidence of a slightly increased load manifested as increased end-diastolic volume and mass.

The relation between left ventricular wall stress shortening and preload changes in ventilated patients

The relation between left ventricular end-systolic wall stress (ESWS) and the velocity of circumferential fibre shortening (Vcfs) was examined in four non-random groups with 12 patients each. In group A, preload was increased by the administration of hydroxyethylstarch 30 mL min-1. In group B, preload was reduced by administering nitroglycerine 4.0 +/- 0.8 mg h-1. A change in pulmonary capillary wedge pressure by 3 mmHg was taken to be the end point for preload manipulation. To assess a change in the relation between ESWS and Vcfs, patients in group C received adrenaline at an infusion rate of 4 g min-1. Patients in group D served as the controls. Geometric variables of ESWS and Vcfs were determined by transoesophageal echocardiography. A linear model was used to assess the relation between ESWS and Vcfs within each group by regression analysis, and analysis of covariance performed to detect significance of intragroup and intergroup differences (P < 0.005). No significant changes were found during preload intervention. With adrenaline, Vcfs increased significantly for a given ESWS. It is concluded that the relation between ESWS and Vcfs, in a multiple patient setting, is independent of modest preload changes and may have the potential to indicate inotropic effects.

The relation between left ventricular wall stress shortening and preload changes in ventilated patients

The relation between left ventricular end-systolic wall stress (ESWS) and the velocity of circumferential fibre shortening (Vcfs) was examined in four non-random groups with 12 patients each. In group A, preload was increased by the administration of hydroxyethylstarch 30 mL min−1. In group B, preload was reduced by administering nitroglycerine 4.0±0.8 mg h−1. A change in pulmonary capillary wedge pressure by 3 mmHg was taken to be the end point for preload manipulation. To assess a change in the relation between ESWS and Vcfs, patients in group C received adrenaline at an infusion rate of 4 g min−1. Patients in group D served as the controls. Geometric variables of ESWS and Vcfs were determined by transoesophageal echocardiography. A linear model was used to assess the relation between ESWS and Vcfs within each group by regression analysis, and analysis of covariance performed to detect significance of intragroup and intergroup differences (P<0.005). No significant changes were found during preload intervention. With adrenaline, Vcfs increased significantly for a given ESWS. It is concluded that the relation between ESWS and Vcfs, in a multiple patient setting, is independent of modest preload changes and may have the potential to indicate inotropic effects.

Improvement of Postreceptor Events by Metoprolol Treatment in Patients With Chronic Heart Failure

Objectives. This study tested the hypothesis that metoprolol restores the reduction of the inotropic effect of the cyclic adenosine monophosphate (cAMP)-phosphodiesterase inhibitor milrinone, which is cAMP dependent but beta-adrenoceptor independent.Background. Treatment with beta-adrenergic blocking agents has been shown to lessen symptoms and improve submaximal exercise performance and left ventricular ejection fraction in patients with heart failure. Restoration of the number of downregulated beta-adrenoceptors has been suggested to be one mechanism of beta-blocker effectiveness. However, the reversal of postreceptor events, namely, an increase in inhibitory G-protein alpha-subunit concentrations, could also play a role.Methods. Fifteen patients with heart failure due to dilated cardiomyopathy (left ventricular ejection fraction 24.6 ± 1.5% [mean ± SD], New York Heart Association functional class II or III) were treated with metoprolol (maximal dose 50 mg three times daily) for 6 months. Before and after metoprolol treatment, inotropic responses to milrinone (5 to 10 μg/kg body weight per min) were measured echocardiographically. For comparison, responses to milrinone were determined under control conditions and after accelerated application of 150 mg of metoprolol to inactivate beta-adrenoceptors in subjects with normal left ventricular function.Results. In subjects with normal left ventricular function, treatment with metoprolol did not alter the increase in fractional shortening or pressure/dimension ratio of circumferential fiber shortening after application of milrinone. In patients with heart failure, treatment with metoprolol significantly increased left ventricular ejection fraction, fractional shortening and submaximal exercise tolerance and reduced heart rate, plasma norepinephrine concentrations and functional class. After metoprolol treatment, milrinone increased fractional shortening but had no effect before beta-blocker treatment.Conclusions. Milrinone increases inotropic performance independently of beta-adrenoceptors in vivo. Metoprolol treatment restores the blunted inotropic response to milrinone in patients with heart failure, indicating that postreceptor events (e.g., increase in inhibitory G-proteins) are favorably influenced. This mechanism could contribute to the beneficial effects observed in the study patients and represents an important mechanism of how beta-blocker treatment influences the performance of the failing heart.