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Auto-antibody against adenine nucleotide translocator in dilated cardiomyopathy and myocarditis--incidence and relation to cardiac function and morphology.

Using an enzyme-linked immunosorbent assay, we measured anti-adenine nucleotide translocater (ANT) antibody in control subjects and in patients with dilated cardiomyopathy (DCM), myocarditis, and other heart disease. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and immunoabsorption tests confirmed accurate purification of the ANT protein and correct measurement of anti-ANT auto-antibody. Anti-ANT antibody was detected in 6 of 37 cases (16%) of DCM and in 5 of 12 cases (42%) of myocarditis. This antibody was not positive in other heart diseases or in apparently healthy controls. There were no differences between anti-ANT autoantibody-positive and -negative DCM or myocarditis patients in any of the cardiac parameters examined (left ventricular ejection fraction, LVEF; left ventricular end-diastolic dimension, LVDd; and cardiothoracic ratio, CTR). Moreover, in patients who were positive for anti-ANT auto-antibody, no positive correlations were found between the parameters and anti-ANT antibody titers in either DCM or myocarditis. Although these results indicate that the detection of anti-ANT antibody was achieved at a high specificity and could have certain diagnostic value in DCM and myocarditis, there was no statistically significant relationship between the cardiac parameters (LVEF, LVDd, and CTR) and anti-ANT antibody titers in either DCM or myocarditis. Some compensatory mechanism of ventricular function may mask the effects of the anti-ANT auto-antibody or alternatively, this auto-antibody may have mimic effects on the pathogenesis and/or progression of DCM and myocarditis.

Adult↗

Assessment of cardiac function by three-dimensional echocardiography compared with conventional noninvasive methods.

BACKGROUND: Reliable, serial, noninvasive quantitative estimation of left ventricular ejection fraction is essential for selecting and timing therapeutic interventions in patients with heart disease. Equilibrium radionuclide angiography is widely used for this purpose but has well-recognized limitations. Advantages of echocardiography over equilibrium radionuclide angiography include assessment of wall motion, valvular pathology, and cardiac hemodynamics, in addition to portability, lack of radiation exposure, and substantially lower cost. However, conventional echocardiographic techniques are limited by geometric assumptions, image positioning errors, and use of subjective visual methods. To overcome these limitations, a three-dimensional echocardiographic method was developed. This study compares ejection fraction by three-dimensional echocardiography, quantitative two-dimensional echocardiography, and subjective two-dimensional echocardiographic visual estimation with that by equilibrium radionuclide angiography. METHODS AND RESULTS: Fifty-one unselected patients with suspected heart disease underwent left ventricular ejection fraction determination by equilibrium radionuclide angiography and three-dimensional echocardiography using an interactive line-of-intersection display and a new algorithm, ventricular surface reconstruction, for volume computation. In 44 patients, ejection fractions were also estimated visually by experienced observers from two-dimensional echocardiography and by quantitative two-dimensional echocardiography using an apical biplane summation-of-disks algorithm. An excellent correlation was obtained between three-dimensional echocardiography and equilibrium radionuclide angiography (r = .94 to .97, SEE = 3.64% to 5.35%; limits of agreement, 10.3% to 13.3%) without significant underestimation or overestimation. SEE values and limits of agreement were twofold to threefold lower than corresponding values for all two-dimensional echocardiographic techniques. In addition, interobserver variability was significantly lower for the three-dimensional echocardiographic method (10.2%) than for the apical biplane summation-of-disks method (26.1%) and subjective visual estimation (33.3%). CONCLUSIONS: Determination of ejection fraction by three-dimensional echocardiography yields results comparable to those obtained by equilibrium radionuclide angiography and is substantially superior to all two-dimensional echocardiographic methods. Therefore, three-dimensional echocardiography may be used for accurate serial quantification of left ventricular function as an alternative to equilibrium radionuclide angiography.

Adolescent↗

Improvement of cardiac function and myocardial energy metabolism of rats with chronic heart failure by long-term coenzyme Q10 treatment.

The effects of long-term treatment with coenzyme Q10 (CoQ10) on myocardial energy metabolism of rats with chronic heart failure (CHF) were examined. Left coronary artery ligation resulted in decreases in blood pressure, left ventricular developed pressure, the first derivative of left ventricular developed pressure, cardiac output and stroke volume indices and caused an increase in left ventricular end-diastolic pressure 12 weeks after the operation. Significant decreases in adenosine-5'-triphosphate, creatine phosphate, creatine and inorganic phosphate contents and the mitochondrial oxygen consumption rate of the viable left and right ventricles were detected in the CHF rat. Oral administration of 5 mg/kg/day CoQ10 for 12 weeks attenuated the changes in the first derivative of left ventricular developed pressure, cardiac output and stroke volume indices of the CHF rat but did not significantly improve the survival of CHF animals. The developed infarct area was approximately 40% of the whole left ventricle, irrespective of treatment with or without CoQ10. There was no reversal in the decreased myocardial CoQ9 and CoQ10 contents of the CHF rat after treatment with exogenous CoQ10. In the right ventricle of CoQ10-treated animals, a significant recovery of creatine, inorganic phosphate and mitochondrial oxygen consumption rate, and a small restoration of creatine phosphate but not of adenosine-5'-triphosphate, were observed, which suggests an appreciable recovery of energy-producing ability in the right ventricle. In contrast, a significant restoration of tissue creatine and inorganic phosphate, but not of other variables, was detected in the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cardiac function at rest and during exercise in normals and in patients with coronary heart disease: evaluation by radionuclide angiocardiography.

This study demonstrates that radionuclide angiocardiography provides a simple and noninvasive approach for evaluation of myocardial function. Previous work concerning myocardial performance has been generally conducted with the patient in the supine position. Radionuclide angiocardiograms were performed in the present study at rest and during exercise in 30 normal subjects and in 30 patients with ischemic coronary artery disease. There were 30 normal controls (Group I), ten with single coronary artery disease (Group II), and 20 patients with multiple vessel coronary disease (Group III). All subjects were studied in the erect posture on a bicycle ergometer. In the normal controls, the mean heart rate doubled and the cardiac output tripled during exercise. Intensive training can lead to extraordinary levels of cardiac performance as shown in a world-class athlete who during peak exercise attained a heart rate of 210, an ejection fraction of 97%, and a cardiac output of 56 litres per minute. In the patients with coronary artery disease, both groups, were able to increase cardiac output to approximately twice the resting value. The magnitude of increase in blood pressure during exercise was not significantly different in the three groups. However, definite changes were present in the end-diastolic volume at rest was 116 and rose to 128 ml in Group I, 93 rising to 132 ml in Group II, and 138 increasing to 216 ml in Group III. The stroke volume increased comparably in all three groups, but the ejection fraction from rest to exercise showed a marked contrast in the controls compared to those with multivessel coronary disease. The ejection fraction rose in Group I from 66 to 80% during exercise, while in Group II it fell from 69 to 67%, and in Group III from 60 to 46%. These findings indicate that patients with ischemic myocardial disease respond to the stress of exercise by cardiac dilatation to maintain of increase stroke volume at increased heart rates. Moreover, the magnitude of this response appears to be greatest in patients with left main coronary artery stenosis. This approach for evaluating myocardial function during exercise provides useful data of importance in selecting medical versus surgical management of patients with ischemic coronary artery disease.

Adult↗

The effects of hormone replacement therapy on echocardiographic basic cardiac functions in postmenopausal women.

This prospective study was designed to investigate the effects of hormone replacement therapy (HRT) on systolic and diastolic functions. Twenty-eight non-smoking, healthy postmenopausal women who had not received any kind of HRT for at least three years within the onset of menopause were included in the study. All patients received 0.625 mg conjugated oestrogens and 2.5 mg medroxyprogesterone acetate as daily HRT regimen. Their basic systolic and diastolic functions were investigated echocardiographically using standard positions and windows before and 6 months after initiation of HRT. The means of age, weight and length of postmenopausal period were 49.3 +/- 5.8 years, 63.5 +/- 8.7 kg and 46.3 +/- 7.1 months, respectively. Heart rate and systolic and diastolic pressures were similar during the pre- and post-treatment periods. After 6 months of HRT, the mean left ventricular end-systolic and end-diastolic volumes were decreased significantly (71.3 +/- 16.4 versus 56.3 +/- 22.8 ml, 144.5 +/- 26.1 versus 111.7 +/- 24.0 ml, respectively, P < 0.05). Left ventricular ejection fraction was increased (45.1 +/- 6.2% versus 54.8 +/- 4.1%, P < 0.05). Improvement in diastolic function was significant compared with the pretreatment period (E/A 0.90 +/- 0.2 versus 1.10 +/- 0.4, deceleration time 238 +/- 36.8 versus 201 +/- 24.2 ms, respectively, P < 0.05). Based on our preliminary results, we conclude that besides the known favourable effects on women's lives, HRT may also improve cardiac performance and age-related dysfunctions. The present results further suggest that oestrogens exert many direct effects on the cardiovascular system, other than the metabolic changes related to lipoproteins.

Blood Pressure↗

Assessment of cardiac function in patients with the acquired immunodeficiency syndrome.

We have assessed right and left ventricular function by multigated radionuclide ventriculography in 12 consecutive patients with acquired immunodeficiency syndrome (AIDS) grouped according to the CDC classification system for HIV infection. Results were correlated with clinical, electrocardiographic and echocardiographic findings. Clinical examination and chest x-ray films showed no evidence of acute cardiac or pulmonary pathology. Five patients had evidence of ventricular dysfunction by radionuclide ventriculography along with significant ECG abnormalities. Three patients had abnormal ECG findings with normal ejection fractions. Echocardiography showed no evidence of significant valvulopathy or pericardial disease except for one patient with fibrinous strands associated with the pericardium. Decreased ejection fractions did not correlate with disease classification, risk group or survival. This study suggests that a major percentage of AIDS patients have some evidence of cardiac abnormalities. We conclude that abnormal ECG findings in an AIDS patient should alert the clinician to possible underlying ventricular dysfunction.

Acquired Immunodeficiency Syndrome↗

[Cardiac function in transient coronary insufficiency after electrophoretic and injection methods of obsidan administration].

The peculiarities of the preventive use of obsidan administered by injection and electrophoresis were studied in experiments on rats with a model of transitory coronary insufficiency. A high efficacy of obsidan was demonstrated irrespective of the route of its administration into the body. This was manifested by a decrease in the rate of cardiac contractions in intact animals and depression of hyperkinetic cardiac reaction in the initial period of myocardial ischemia. The unfavourable inotropic and the antiarrhythmic effects of the agent were less in electrophoretic administration than in injection.

Animals↗

Heart rate variability and hemodynamic alterations in canines with normal cardiac function during exposure to pressure support, continuous positive airway pressure, and a combination of pressure support and continuous positive airway pressure.

Variations in intrathoracic pressure generated by different ventilator weaning modes may significantly affect intrathoracic hemodynamics and cardiovascular stability. Although several investigators have attributed cardiovascular alterations during ventilator weaning to augmented sympathetic tone, there is limited investigation of changes in autonomic tone during ventilator weaning. Heart rate variability (HRV), the analysis of beat-to-beat changes in heart rate, is a noninvasive indicator of autonomic tone that might be useful in the identification of patients who are at risk for weaning difficulty due to underlying cardiac dysfunction. The authors describe HRV and hemodynamics in response to 3 ventilatory conditions: pressure support (PS) 10 cmH2O, continuous positive airway pressure (CPAP) 10 cmH2O, and a combination of PS 10 cmH2O and CPAP 10 cmH2O (PS + CPAP) in a group of canines with normal ventricular function. Six canines were studied in the laboratory. Continuous 3-lead electrocardiographic data were collected during baseline (controlled mechanical ventilation) and following transition to each of the ventilatory conditions (PS, CPAP, PS + CPAP) for analysis of HRV. HRV was evaluated using power spectral analysis to define the power under the curve in a very low frequency range (0.0033 to < 0.04 Hz, sympathetic tone), a low frequency range (0.04 to < 0.15 Hz, primarily sympathetic tone), and a high frequency range (0.15 to < 0.40 Hz, parasympathetic tone). A thermodilution pulmonary artery catheter measured cardiac output and right ventricular end-diastolic volume to describe global hemodynamics. There were significant increases in very low frequency power (sympathetic tone) with a concomitant significant reduction in high-frequency power (parasympathetic tone) with exposure to PS + CPAP. These alterations in HRV were associated with significantly increased heart rate and reduced right ventricular end-diastolic volume. Although there was a small but significant increase in cardiac output with exposure to PS, HRV was unchanged. These data indicate that there was a relative shift in autonomic balance to increased sympathetic and decreased parasympathetic tone with exposure to PS + CPAP. The increase in intrathoracic pressure reduced right ventricular end-diastolic volume (preload). This hemodynamic alteration generated a change in autonomic tone, so that cardiac output could be maintained. Individuals with autonomic and/or cardiovascular dysfunction may not be capable of this type of response and may fail to successfully wean from mechanical ventilation.

Analysis of Variance↗

Vasopressin reduces cardiac function and augments cardiopulmonary baroreflex resistance increases in man.

We examined the effects of physiologic infusions of arginine vasopressin (AVP) on cardiovascular hemodynamics and on reflex responses initiated by decreasing cardiopulmonary baroreceptor stimulation (with lower body negative pressure) in 10 healthy, captopril-pretreated young men (19-27 yr). Their responses were compared with those of four volunteers given isosmotic infusion. Heart rate, stroke volume, blood pressure, and forearm blood flow were measured by electrocardiography, impedance cardiography, radial artery cannulation, and strain gauge plethysmography. Two 55-min infusions of AVP at rates of 0.15 and 0.40 ng/kg per min increased average plasma concentrations from control levels of 5 pg/ml to 18 and 36 pg/ml, respectively. These infusions resulted in progressive reductions of heart rate and cardiac output and increases of forearm and total peripheral resistance. Blood pressure increases were significant only during the larger AVP infusion rate. Lower body negative pressure provoked reflex increases of total peripheral resistance. These increases were enhanced 60% during AVP infusion compared with increases during control (pre-AVP). Baseline measurements and reflex responses were unchanged by isosmotic infusions. These results demonstrate that AVP has profound effects on cardiovascular function and augments cardiopulmonary baroreflex-mediated increases of peripheral resistance in man.

Adolescent↗

Opening the pericardium during pulmonary artery constriction improves cardiac function.

During acute pulmonary hypertension, both the pericardium and the right ventricle (RV) constrain left ventricular (LV) filling; therefore, pericardiotomy should improve LV function. LV, RV, and pericardial pressures and RV and LV dimensions and LV stroke volume (SV) were measured in six anesthetized dogs. The pericardium was closed, the chest was left open, and the lungs were held away from the heart. Data were collected at baseline, during pulmonary artery constriction (PAC), and after pericardiotomy with PAC maintained. PAC decreased SV by one-half. RV diameter increased, and septum-to-LV free wall diameter and LV area (our index of LV end-diastolic volume) decreased. Compared with during PAC, pericardiotomy increased LV area and SV increased 35%. LV and RV compliance (pressure-dimension relations) and LV contractility (stroke work-LV area relations) were unchanged. Although series interaction accounts for much of the decreased cardiac output during acute pulmonary hypertension, pericardial constraint and leftward septal shift are also important. Pericardiotomy can improve LV function in the absence of other sources of external constraint to LV filling.

Animals↗

Increased periconceptual maternal glycated haemoglobin in diabetic mothers reduces fetal long axis cardiac function.

OBJECTIVE: To compare ventricular long axis function in fetuses of diabetic mothers (FDM) with contemporaneously studied normal controls (N) and to assess the effect of pre-pregnancy diabetic control on these measurements. DESIGN: Long axis function was compared in 41 FDM and 159 N fetuses in a cross sectional observational study. SETTING: Fetal medicine unit. METHODS AND RESULTS: Echocardiography confirmed structural normality. Pulsed wave valvar Doppler velocimetry, lengthening and shortening myocardial velocities, and amplitude of ventricular long axis movement were recorded at the base of the left and right ventricular free walls and septum. Periconceptual diabetic control was assessed by haemoglobin A1c (HbA1c) in early pregnancy. Doppler and myocardial velocities were negatively related and myocardial thickness was positively related with HbA1c. In both cohorts all variables except mitral and tricuspid late filling (A wave) velocities were dependent on gestational age. FDM gestational age related values were higher for most variables and robust analysis of covariance showed significantly different maturation patterns in mitral valve E:A ratio (p = 0.036) and pulmonary velocity (p = 0.04), late lengthening myocardial velocities (left p = 0.016 and right p = 0.066), left myocardial shortening velocities (p = 0.008), and left free wall (p = 0.03) and septal (p = 0.04) amplitude of motion. FDM septal thickness was significantly increased throughout gestation (p < 0.0001). CONCLUSION: Periconceptual diabetic control influences fetal cardiac performance and myocardial hypertrophy but, unlike the pathophysiology of adult ventricular hypertrophy, is accompanied by functional adaptation. It is unlikely to explain the increased rate of late stillbirth observed in diabetic pregnancies.

Adult↗

Cardiac function of an acute ischemic heart failure model produced by microsphere injection into the left coronary artery. Pressure-volume relationship as determined by a conductance catheter.

The authors produced an acute canine heart failure model by injecting microspheres (phi 15.5 +/- 0.1 mm, 5 x 10(5)) into the left coronary artery, and characterized the model in terms of the pressure-volume relationship obtained by the conductance catheter method. Cardiodynamics of the microsphere injection group (M group: n = 10) and control group (C group: n = 12) were studied with 1) heart rate, 2) aortic pressure, 3) cardiac output (CO), 4) maximal ventricular elastance, 5) effective arterial elastance/maximal ventricular elastance, and 6) external work/pressure-volume area efficiency. With microsphere injection, CO and external work/pressure-volume area efficiency significantly decreased. With administration of dobutamine (5 mg/kg/min), CO and maximal ventricular elastance recovered to normal and aortic pressure became higher than normal. These changes in heart rate, aortic pressure, CO, maximal ventricular elastance, and external work/pressure-volume area efficiency in the M group were comparable in percentage to those in the C groups. Cardiodynamics of this heart failure model generally were stable for 3 hrs after microsphere injection. The authors concluded that this model would be an excellent acute heart failure model for investigating hemodynamic effects of circulatory assist devices.

Animals↗

A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery.

Heparin and protamine are the standard anticoagulant-antidote regimen used in almost every cardiopulmonary bypass (CPB) procedure even though both are associated with an array of complications and toxicities. Here we demonstrate that an anticoagulant aptamer-antidote pair targeting factor IXa can replace heparin and protamine in a porcine CPB model and also limit the adverse effects on thrombin generation, inflammation, and cardiac physiology associated with heparin and protamine use. These results demonstrate that targeting clotting factors upstream of thrombin in the coagulation cascade can potentially reduce the perioperative pathologies associated with CPB and suggest that the aptamer-antidote pair to FIXa may improve the outcome of patients undergoing CPB. In particular, this novel anticoagulant-antidote pair may prove to be useful in patients diagnosed with heparin-induced thrombocytopenia or those who have been sensitized to protamine, particularly patients who have insulin-dependent diabetes.

Animals↗

Cardiac function in rats selectively bred for low- and high-capacity running.

Rat genetic models of intrinsic (i.e., untrained) low-capacity runners (LCR) and high-capacity runners (HCR) are being developed by artificial selective breeding for treadmill running. At generation 3, these lines differed in running capacity by 114%. We used generation 3 rats to test the hypotheses that HCR, relative to LCR, have 1) greater isolated cardiac performance and 2) more resistance to myocardial ischemic insult. The LCR ran for 227 +/- 7 m, and the HCR ran 994 +/- 11 m at exhaustion (337% difference, P < 0.001). Isolated heart performance was assessed from cardiac output (CO) generated at constant preload (15 mmHg) and afterload (70 mmHg) using a Langendorff-Neely working heart preparation. CO averaged 33.5 +/- 2.0 ml. min(-1). g(-1) in LCR hearts and 49.9 +/- 1.4 ml. min(-1). g(-1) in HCR hearts (49% difference, P < 0.001). Recovery of CO after 25 min of global ischemia was not different between the lines. These results suggest that 1) increased cardiac performance accounts for part of the difference in running capacity between the lines; and 2) unlike exercise training, genetically determined intrinsic capacity for exercise does not influence the recovery from 25 min of global low-flow cardiac ischemia.

Animals↗