Effect of various beta-adrenolytic drugs and calcium channel blocker (nifedipine) on selected indicators of calcium-phosphorus metabolism in patients with hyperthyroidism and simple goiter

The study was aimed at evaluation of the effect of short-term treatment with one of the six beta adrenolytic drugs (propranolol, metoprolol, atenolol, pindolol, nadolol, acebutolol) and calcium antagonist nifedipine on the values of several parameters of calcium-phosphorus metabolism in 81 patients with hyperthyroidism (14 patients with Graves' disease, and 67 patients with toxic nodular goiter), and 82 patients with simple goiter. The patients studied have been divided into seven groups, each receiving one of the investigated drugs during four days. A significant decrease in the urinary excretion of hydroxyproline was found only in the patients with hyperthyroidism receiving propranolol. This effect of propranolol on hydroxyprolinuria was not related to the degree of lowering of serum T3 concentration observed in these patients.     

Effect of ectopic excitation on the ventricular pump function in chicken

The pump function of the heart ventricles was studied in chest-open anaesthetized adult female chickens under sinus rhythm and ectopic excitation of different localization. The intraventricular pressure in the right and left heart ventricles was measured by insertion of catheters through the ventricular free walls. Maximum systolic pressure, end-diastolic pressure, contractility (dP/dtmax) and relaxation (dP/dtmin) of both heart ventricles, and duration of the asynchronous contraction time of the left ventricle were analyzed. It was revealed that reduction of the pump function of the left ventricle tends to be greater under right ventricular ectopic excitation compared with left ventricular one. In comparison with the sinus rhythm, the pump function of the right ventricle was preserved to a greater extent under stimulation of the left ventricular apex and was significantly impaired under right ventricular ectopic excitation. Relaxation of both heart ventricles was more susceptible to ventricular ectopic excitation than contractility, and was more vulnerable in the right ventricle than in the left one. The direction of changes of the pump function of the heart ventricles in chickens under ventricular ectopic excitation was similar to changes of the pump function of mammalian hearts.     

Intérêt du dosage de la thyroglobulinémie chez les sujets porteurs du goitre en zones de déficience iodée au Bénin

In the present study, we analyze the results of thyroid hormones and thyroglobulinemia of 162 patients with goiter living in the departments of Collines and Donga, known to be areas of iodine deficiency in Benin. These results are compared with those of 85 healthy subjects living in the same departments. This study is a cross-sectional analytical study carried out from 1st July 2009 to 30th June 2010. The population of patients consisted of seven males and 155 females. The average age was of 45.7 years. Most of the patients were suffering of simple goiter. Only six of them had thyroid nodules. The diagnosis of biological hyperthyroidism was positive for 20 patients; 16 of them had subclinical hypothyroidism and four clinical hyperthyroidism. One case of clinical hypothyroidism was found. All other 141 patients were biologically normal (euthyroidism). Seventeen of the patients (including six patients presenting a thyroid nodule) had a normal thyroglobulin rate. Hyperthyroglobulinemia was observed in all other 145 patients. These results suggest that patients with goiter in zone of iodine deficiency are biologically euthyroid with hyper-thyroglobulinemia. Thyroglobulin dosage is then recommended, especially when nodules are perceptible.     

Shifts in the heart left ventricle function in patients with pulmonary tuberculosis during adequate chemotherapy

To investigate the hemodynamics and myocardic contraction of the heart left ventricle, 61 patients with pulmonary tuberculosis (main group) and 26 healthy subjects (control group) were observed. Higher ultimate systolic and diasystolic volumes of the left ventricle and lower levels of the efflux fraction in the patients with active pulmonary tuberculosis were stated. There was shown inverse correlation of the systemic systolic arterial pressure and the left ventricle efflux fraction with ESR, evident of the tuberculosis intoxication. The most pronounced aggravation of the left ventricle function was recorded in the patients with the most severe tuberculosis process. The impairments in the left ventricle in the patients with active pulmonary tuberculosis were of functional nature. Due to intensive therapy of the tuberculosis, the indices of the left ventricle efflux function improved and the systemic arterial pressure came to normal, along with elimination of the tuberculosis intoxication signs.     

Changes in plasma fibronectin levels in thyroid diseases

The plasma levels of fibronectin (Fn) have been measured in normal subjects and in patients with thyroid diseases. The mean plasma Fn levels in 62 normal adults was 32.0 +/- 6.0 mg/dl, whereas it was elevated to 62.6 +/- 16.1 mg/dl (mean +/- SD) in 25 patients with hyperthyroidism and decreased to 19.2 +/- 8.0 mg/dl in 9 patients with hypothyroidism. The 9 patients with simple goiter have normal values of 29.1 +/- 8.0 mg/dl. With the administration of anti-thyroid drugs, plasma Fn levels normalized, with a time lag, in parallel with normalization of the thyroid function. Positive correlation was obtained between Fn levels and serum levels of triiodothyronine (T3) and thyroxine (T4). The present findings indicate that measurement of plasma Fn both in the basal state and during treatment provides evidence of altered Fn metabolism in thyroid diseases and serves to follow up the effect of treatment.     

Haemodynamic effects of beta-adrenergic blockade in hyperthyroid patients with and without heart failure.

Haemodynamic studies were performed in 10 patients with uncomplicated thyrotoxicosis and seven with thyrotoxic cardiac failure. The cardiac output of those with uncomplicated hyperthyroidism was higher than normal at rest. After 2 mg of intravenous propranolol there was a 13% fall but the level was still higher than normal. In patients with thyrotoxic cardiac failure the resting cardiac output was normal, but it fell after propranolol by 30% to subnormal levels. In both groups there was an increase in right heart pressures and fall in the rate of increase in arterial pressure, which indicated a decrease in myocardial contractility. These results indicate that increased autonomic activity is a compensatory phenomenon in hyperthyroid heart failure and that its abolition by beta-blocking drugs has a deleterious effect on cardiac function. They are therefore contraindicated in patients with thyrotoxic heart failure.     

Continuum rheology of muscle contraction and its application to cardiac contractility.

A set of constitutive equations is proposed to describe the mechanics of contraction of skeletal and heart muscle. Fiber tension is assumed to depend on the degree of chemical activation, the stretch ratio, and the rate of stretching of the fibers. The time rate of change of activation is governed by a differential equation. The proposed constitutive equations are used to model the time courses of isotonic and isometric twitches during contraction and relaxation phases of the muscle response to stimulation. Various contractility indices of the left ventricle are considered next by using the proposed constitutive equations. The present analysis introduces a new interpretation of the index of contractility (dP/dt)/P used in cardiac literature. It is shown that this index may not be related at all to the maximum speed of shortening and that it may be dependent on both preload and afterload. The development of pressure during isovolumetric contraction of the left ventricle is shown to be governed by a differential equation describing the time rate of change of tension during isometric contraction of myocardium fibers.     

Arterial hypertension associated with hyper and hypothyroidism]

45 patients with hyper and hypothyroidism in the time 1989-1990 were observed. The Graves' disease was diagnosed in 29 and rather in the younger patients, but 16 had the toxic nodular goiter and those were elderly. In 27 the hypertension was secondary (symptomatic) and after the successful treatment of the hyperthyroidism was completely controlled. In 14 cases the hypertension was primary (essential) and the application of the hypotensive drugs was also necessary. Among 4 patients with primary hypothyroidism and associated hypertension and coronary insufficiency the early treatment by the thyroid preparation was successful: the blood pressure was lowered and the coronary insufficiency was improved; but if the replacement therapy was stopped and the hypothyroidism was relapsed, the blood pressure was increases and the coronary insufficiency was aggravated. Conclusions: 1. The secondary (symptomatic) hypertension associated with the hyperthyroidism may be controlled by successful treatment of the thyrotoxicosis, but the primary (essential) must be treated by the hypotensive drugs also. 2. The early treatment of the hypothyroidism may control the associated hypertension and the coronary insufficiency. 3. Graves' disease is associated mostly with symptomatic hypertension, in nodular toxic goiter in most of the cases the essential hypertension was established.     

Left ventricular response to sublingual administration of nitroglycerin

The aim of this study was to investigate whether the rapid improvement of the clinical condition of patients after administration of nitroglycerin can be documented objectively using the apexcardiogram. The study was performed on 28 male patients with coronary heart disease whose clinical condition allowed us to perform the initial polygraphic examination during an attack of angina pectoris. The heart rate and three apexcardiographic indexes were determined from non-invasive polygraphic tracings. The first index was the a/H (ratio: amplitude of apexcardiographic "a" wave to total amplitude of apexcardiogram). The second and third were the velocity of the anterior left ventricular wall motion during both isovolumic contraction (VwmC) and isovolumic relaxation (VwmR) of the left ventricle. The mean differences from initial values were calculated after 2, 4, 6 and 10 min following administration of nitroglycerin. Significant changes already occurred during the second minute after administration of nitroglycerin. All parameters remained significantly changed up to the 10th minute after this treatment. According to our results, the cardiovascular response to sublingual administration of nitroglycerin can be objectively evaluated by apexcardiography.     

Computational modeling of left heart diastolic function: examination of ventricular dysfunction

A computational model that accounts for blood-tissue interaction under physiological flow conditions was developed and applied to a thin-walled model of the left heart. This model consisted of the left ventricle, left atrium, and pulmonary vein flow. The input functions for the model included the pulmonary vein driving pressure and time-dependent relationship for changes in chamber tissue properties during the simulation. The Immersed Boundary Method was used for the interaction of the tissue and blood in response to fluid forces and changes in tissue pathophysiology, and the fluid mass and momentum conservation equations were solved using Patankar's Semi-Implicit Method for Pressure Linked Equations (SIMPLE). This model was used to examine the flow fields in the left heart under abnormal diastolic conditions of delayed ventricular relaxation, delayed ventricular relaxation with increased ventricular stiffness, and delayed ventricular relaxation with an increased atrial contraction. The results obtained from the left heart model were compared to clinically observed diastolic flow conditions, and to the results from simulations of normal diastolic function in this model [1]. Cases involving impairment of diastolic function were modeled with changes to the input functions for fiber relaxation/contraction of the chambers. The three cases of diastolic dysfunction investigated agreed with the changes in diastolic flow fields seen clinically. The effect of delayed relaxation was to decrease the early filling magnitude, and this decrease was larger when the stiffness of the ventricle was increased. Also, increasing the contraction of the atrium during atrial systole resulted in a higher late filling velocity and atrial pressure. The results show that dysfunction can be modeled by changing the relationships for fiber resting-length and/or stiffness. This provides confidence in future modeling of disease, especially changes to chamber properties to examine the effect of local dysfunction on global flow fields.     

Structure of the cardiac systole in mammals and birds

The comparative analysis of the contractile function of the heart left ventricle in four species of homoeothermic tetrapods (chicken, quail, rat, sheep) who differ in their spatio-temporal pattern of ventricular excitation, heart rate, and heart weight was performed. The analysis of cardiac cycle structure was performed on the basis of synchronous recording of ECG, phonocardiogram, and apex cardiogram. Indices of myocardial contractility of the left ventricle calculated on the basis of the analysis of the cardiac dynamics indicate disadvantageous contractile function of the left ventricle in rodents and non-flying birds in comparison with sheep. The functioning of the left ventricle in male rats is more strained than in female rats. One fundamental factor determining a more strained functioning of the left ventricle in birds in comparison with mammals is the heart rate. The relative weight and activation pattern of the left ventricular myocardium govern the contractile function of the left ventricle to a lesser extent.     

Myosin types and fiber types in cardiac muscle. I. Ventricular myocardium

Antisera against bovine atrial myosin were raised in rabbits, purified by affinity chromatography, and absorbed with insolubilized ventricular myosin. Specific anti-bovine atrial myosin (anti-bAm) antibodies reacted selectively with atrial myosin heavy chains, as determined by enzyme immunoassay combined with SDS-gel electrophoresis. In direct and indirect immunofluorescence assay, anti-bAm was found to stain all atrial muscle fibers and a minor proportion of ventricular muscle fibers in the right ventricle of the bovine heart. In contrast, almost all muscle fibers in the left ventricle were unreactive. Purkinje fibers showed variable reactivity. In the rabbit heart, all atrial muscle fibers were stained by anti-bAm, whereas ventricular fibers showed a variable response in both the right and left ventricle, with a tendency for reactive fibers to be more numerous in the right ventricle and in subepicardial regions. Diversification of fiber types with respect to anti-bAm reactivity was found to occur during late stages of postnatal development in the rabbit heart and to be influenced by thyroid hormone. All ventricular muscle fibers became strongly reactive after thyroxine treatment, whereas they became unreactive or poorly reactive after propylthiouracil treatment. These findings are consistent with the existence of different ventricular isomyosins whose relative proportions can vary according to the thyroid state. Variations in ventricular isomyosin composition can account for the changes in myosin Ca2+-activated ATPase activity previously observed in cardiac muscle from hyper- and hypothyroid animals and may be responsible for the changes in the velocity of contraction of ventricular myocardium that occur under these conditions. The differential distribution of ventricular isomyosins in the normal heart suggests that fiber types with different contractile properties may coexist in the ventricular myocardium.     

Clinical observations and echocardiographic features of mural thrombi in the left ventricle during myocardial infarction]

The incidence and changes in the mural thrombi in left ventricle in ECHO-2D in the acute myocardial infarction as well as relationship between clinical parameters and echocardiographic indices of the left cardiac ventricle contractability asynergy and dynamics of changes in mural thrombi have been investigated. The studies included 137 consecutive patients (98 males and 39 females) treated for the acute myocardial infarction. Patients' age ranged from 35 to 87 years (mean 62 years). Infarction of the anterior and/or lateral wall was diagnosed in 67 patients, and infarction of the inferior and/or posterior wall in 70 patients. Mural thrombi were diagnosed in 42 (31%) patients. Eighteen thrombi (43%) were liquefied during hospitalization. Comparative analysis of patients in whom mural thrombi underwent liquefaction in the hospital and a group of patients with myocardial infarction and persisting mural thrombi showed that return of left ventricle movements with subsequent contractability facilitate liquefaction of mural thrombi. Higher mortality rate in the group of patients with myocardial infarction with mural thrombi is due to extension of the infarction accompanied by marked asynergy of left ventricular contractions which does not decrease in sequential examinations, and increasing congestive heart failure.     

Changes in myosin isozyme expression during cardiac hypertrophy in hyperthyroid rabbits

The myosin isozyme distribution in the left ventricle and in the interventricular septum of rabbits was studied after 3, 7, 11, 14 and 21 days of L-thyroxine (500 micrograms/kg/day) administration. Histochemical procedures were employed to identify V1 and V3 by their Ca2+ ATPase activity and their proportions were quantified through polyacrylamide gel electrophoresis. In the left ventricle, the subepicardium was the first to show the shift from V3 to V1, followed by the subendocardium. The intermediate region became heterogeneous by 11 days and remained so until 21 days. The right subendocardial and the intermediate regions of the interventricular septum were heterogeneous in the normal rabbit and hyperthyroidism resulted in a shift from V3 to V1 in both the right and left subendocardial regions of the septum. Like the left ventricle, the intermediate region of the interventricular septum remained heterogeneous. Localized accumulations of collagen were seen in all regions of the left ventricle and interventricular septum. From these results we conclude that in thyrotoxic myocardial hypertrophy the isozymic shift from V3 to V1 is progressive, region-specific and is directly correlated with the period of hyperthyroidism in the first 2 weeks. Prolonged hyperthyroidism results in localized accumulation of collagen which does not exhibit any regional specificity.     

大鼠心力衰竭模型的构建与鉴定

目的比较主动脉弓缩窄和腹主动脉缩窄复制心力衰竭衰模型的异同,探索快速有效的心衰动物模型。方法将大鼠分为主动脉缩窄手术组,腹主动脉缩窄手术组和对照组（C组）。主动脉缩窄手术组实施颈部手术,在主动脉弓处缩窄动脉直径;腹主动脉缩窄手术组实施腹部手术,在腹主动脉处缩窄动脉直径;C组实施颈部手术但不实施动脉缩窄手术。各组实验动物均正常喂养4～6周后进行心脏的超声检测和心脏血流动力学检测。结果心脏超声结果显示：主动脉弓缩窄手术组左心室壁厚度和左心室腔内径在术后4周明显高于正常组;而腹主动脉缩窄手术组左心室壁厚度和左心室腔内径在术后4周较正常组没有明显增加。术后6周,腹主动脉缩窄手术组左心室壁厚度和左心室腔内径都明显增加,而主动脉弓缩窄手术组左心室壁厚度没有明显改变,左心室腔内经明显增加。血流动力学指标显示：主动脉弓缩窄手术组LVESP、LVEDP、LVDP、±dp/dtmax都明显低于腹主动脉缩窄手术组。结论主动脉弓缩窄手术复制心肌肥大导致心功能衰竭模型效果明显快于腹主动脉缩窄手术复制的心肌肥大导致心功能衰竭模型。     

Stretch of contracting cardiac muscle abruptly decreases the rate of phosphate release at high and low calcium

The contractile performance of the heart is linked to the energy that is available to it. Yet, the heart needs to respond quickly to changing demands. During diastole, the heart fills with blood and the heart chambers expand. Upon activation, contraction of cardiac muscle expels blood into the circulation. Early in systole, parts of the left ventricle are being stretched by incoming blood, before contraction causes shrinking of the ventricle. We explore here the effect of stretch of contracting permeabilized cardiac trabeculae of the rat on the rate of inorganic phosphate (P(i)) release resulting from ATP hydrolysis, using a fluorescent sensor for P(i) with millisecond time resolution. Stretch immediately reduces the rate of P(i) release, an effect observed both at full calcium activation (32 μmol/liter of Ca(2+)), and at a physiological activation level of 1 μmol/liter of Ca(2+). The results suggest that stretch redistributes the actomyosin cross-bridges toward their P(i)-containing state. The redistribution means that a greater fraction of cross-bridges will be poised to rapidly produce a force-generating transition and movement, compared with cross-bridges that have not been subjected to stretch. At the same time stretch modifies the P(i) balance in the cytoplasm, which may act as a cytoplasmic signal for energy turnover.     

Effects of hyperthyroidism on delayed rectifier K+ currents in left and right murine atria

Hyperthyroidism has been associated with atrial fibrillation (AF); however, hyperthyroidism-induced ion channel changes that may predispose to AF have not been fully elucidated. To understand the electrophysiological changes that occur in left and right atria with hyperthyroidism, the patch-clamp technique was used to compare action potential duration (APD) and whole cell currents in myocytes from left and right atria from both control and hyperthyroid mice. Additionally, RNase protection assays and immunoblotting were performed to evaluate the mRNA and protein expression levels of K(+) channel alpha-subunits in left and right atria. The results showed that 1) in control mice, the APD was shorter and the ultra-rapid delayed rectifier K(+) conductance (I(Kur)) and the sustained delayed rectifier K(+) conductance (I(ss)) were larger in the left than in the right atrium; also, mRNA and protein expression levels of Kv1.5 and Kv2.1 were higher in the left atrium; 2) in hyperthyroid mice, the APD was shortened and I(Kur) and I(ss) were increased in both left and right atrial myocytes, and the protein expression levels of Kv1.5 and Kv2.1 were increased significantly in both atria; and 3) the influence of hyperthyroidism on APD and delayed rectifier K(+) currents was more prominent in right than in left atrium, which minimized the interatrial APD difference. In conclusion, hyperthyroidism resulted in more significant APD shortening and greater delayed rectifier K(+) current increases in the right vs. the left atrium, which can contribute to the propensity for atrial arrhythmia in hyperthyroid heart.     

Protein synthesis during right-ventricular hypertrophy after pulmonary-artery stenosis in the dog.

The rate of protein synthesis in the heart of normal dogs and those with pulmonary-artery stenosis was measured by a continuous intravenous infusion of [14C]tyrosine. The protein-synthesis rate of both ventricles was the same in normal dogs and averaged 7.5% per day. The right ventricle hypertrophied rapidly after the acute imposition of pulmonary-artery stenosis, the wet weight increasing by 84% after 24 days, with the rate of increase being most rapid over the first 5 days. The left ventricle remained largely unaffected and served as an internal control. During hypertrophy there was an increased incorporation of [14C]tyrosine into protein without a significant change in the specific radioactivity of free tyrosine in the ventricles. After 5 days of stenosis the synthesis rate of the total mixed proteins of the right ventricle had increased to 13.6% per day, compared with 6.2% in the control left ventricle. This increase in synthesis was reflected in both the myofibrillar and sarcoplasmic proteins. After 5 days the protein-synthesis rate decreased, but still remained significantly elevated above that in the control left ventricle by 24 days of stenosis.     

Spectrum analysis of transient phenomena of the left ventricular pressure.

The application of "real time" spectrum analysis to left ventricular pressure during transient phenomena is described. Transient phenomena generated by the injection of drugs (norepinephrine-isoproterenol), anoxia and occlusion of aorta and carotids show sudden changes in the frequency of heart contraction. Propranolol stabilizes the heart rate in similar circumstances.     

Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. I. Mechanical activity.

Long-lasting cardioprotection may be attained by chronic hypoxia. The basal parameters of contractile function and their response to hypoxia/reoxygenation were measured under isometric conditions, in papillary muscles isolated from left ventricle of rats that were submitted to 53.8 kPa in a hypobaric chamber from 7 wk of age and for their lifetime and of their siblings kept at 101.3 kPa. During acclimatization, hematocrit increased, body weight gain decreased, and heart weight increased with right ventricle hypertrophy. Papillary muscle cross-sectional area was similar in both control and hypoxic groups up to 45 wk of exposure. Developed tension (DT) was 34-64% higher in rats exposed to hypoxia for 10, 26, and 45 wk than in their age-matched controls, whereas resting tension was unchanged. Maximal rates of contraction and relaxation showed a similar pattern of changes as DT. Recovery of DT and maximal rates of contraction and relaxation after 60-min hypoxia and 30-min reoxygenation was also improved in adult hypoxic rats to values similar to those of young rats. Heart acclimatization was lost after 74 wk of exposure. Results are consistent with the development of cardioprotection during high-altitude acclimatization and provide an experimental model to study the mechanisms involved, which are addressed in the accompanying paper.