Iodine 123-metaiodobenzylguanidine imaging reflect generalized sympathetic activation in patients with left ventricular dysfunction

BACKGROUND: Iodine 123-metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. To determine the role of MIBG imaging as a measure of generalized sympathetic nerve activity, MIBG imaging was evaluated with muscle sympathetic nerve activity (MSNA) and plasma norepinephrine (noradrenaline) level in patients with old myocardial infarction. METHODS: Myocardial MIBG scintigraphy, MSNA and plasma norepinephrine measurement were performed within 3 days in 35 patients with old myocardial infarction. Patients were divided into three groups according to their ejection fraction (EF); preserved (EF > or = 50%, 12 patients), intermediate (35% < EF < 50%, 13 patients), or depressed (EF < or = 35%, 10 patients).The heart to mediastinum (H/M) ratio was obtained 4 h after tracer injection from the chest anterior view image. MIBG washout rate was calculated from the early and delayed images. MSNA was recorded by microneurography. RESULTS: Plasma norepinephrine level had weak negative correlations with early H/M ratio (r = 0.37, P<0.05) and delayed H/M ratio (r = 0.33, P<0.05), and a positive correlation with MIBG washout rate (r = 0.54, P<0.01). MSNA had weak negative correlations with early H/M ratio (r = 0.51, P<0.05) and delayed H/M ratio (r = 0.52, P<0.05). However, a strong correlation was found between MSNA and MIBG washout rate (r = 0.88, P<0.001). Despite no significant differences in plasma norepinephrine level and H/M ratio, patients with intermediate and depressed EF had higher MIBG washout rate and MSNA compared with those with preserved EF. CONCLUSIONS: Increased in cardiac sympathetic nerve activity was associated with augmented sympathetic outflow of the skeletal muscle and hence, MIBG washout rate allow the assessment of general sympathetic nerve activity.     

Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy

Background: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood. Methods and results: We studied 99 patients with IDC (age 54 ± 1 years, left ventricular ejection fraction (EF) 40 ± 1%, maximum oxygen uptake (VO₂max) 20 ± 1 ml kg^?1 min^?2, mean ± SEM) by using ¹²³I‐metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)‐ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)‐6 and N‐terminal B‐type natriuretic peptide (NT‐proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL‐6 (r = 0·42, P<0·001 and r = ?0·31, P<0·01) and NT‐proBNP (r = 0·48, P<0·001 and r = ?0·40, P<0·001). During a median follow‐up of 4·1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter–defibrillator). In these patients, MIBG washout was higher (53 ± 4 versus 40 ± 2%, P = 0·01) and H/M ratio lower (1·38 ± 0·04 versus 1·51 ± 0·02, P = 0·01) than in patients without an event. Conclusions: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.     

Abnormality of the left ventricular sympathetic nervous function assessed by I-123 metaiodobenzylguanidine imaging in pediatric patients with neurocardiogenic syncope

The purpose of this study was to assess the left ventricular sympathetic nervous system function in the patients with neurocardiogenic syncope (NCS) using I-123 metaiodobenzylguanidine (MIBG) imaging of the heart, and to compare the plasma noradrenaline (NA) and MIBG results of tilt positive and tilt negative patients following a head-up tilt test (HUT). The study included 30 patients. Their physical and laboratory examinations did not show a pathology that may be the cause of their syncope. HUT test was positive in 13 patients and negative in 17 patients. Plasma NA concentrations were higher in the HUT positive than the HUT negative group at the beginning and at the 10th minute of the test. Specific I-123 MIBG uptake assessed as the cardiac to mediastinal activity ratio in the delayed image was significantly higher in HUT positive group. The higher levels of MIBG uptake and plasma NA observed in HUT positive patients may reflect the greater capacity of NA storage in cardiac adrenergic neuronal tissue in patients with NCS. The results of this study support the critical role of autonomic nervous system in the pathophysiology of NCS and the excessive sympathetic nervous stimulation as the trigger of paradox reflex.     

The myocardial condition in chronic obstructive pulmonary disease and bronchial asthma

The purpose of the study was to assess the influence of structural and functional changes in the myocardium of the right and left ventricle (RVand LV) on the development of ischemia and arrhythmia in chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA). The subjects of the study were 156 patients with either persistent BA (81 patients) or COPD (75 patients). Patients with decompensated cor pulmonale were excluded. ECG, 24-hour ECG monitoring, and echocardioscopy were performed. The study found that the occurrence of supraventricular and ventricular extrasystoles (SVES and VES) in patients with mild COPD or BA depended on the condition of RV diastolic function and on LV diastolic function and myocardial ischemia as well in COPD. In moderate BA the processes of myocardial remodeling correlate with myocardial ischemia, RV dysfunction and increased pulmonary arterial pressure (PAP), as well as with lipid dismetabolism. The appearance of SVES in patients with severe BA is connected with interventricular septal hypertrophy, LV dysfunction, and increased PAP, while VEC appear due to myocardial ischemia and hypercholesterolemia. In severe COPD the occurrence of SVES and VES does not depend on structural and functional changes in the myocardium, while myocardial ischemia is connected with LV hypertrophy. In BA ischemia depends on the development of RV and LV diastolic dysfunction, as well as hypercholesterolemia.     

Myocardial ischemia and paroxysmal cardiac arrhythmia in different severity of bronchial asthma

The study was undertaken to define the prevalence and pattern of myocardial ischemia and cardiac arrhythmia in patients with persistent bronchial asthma (BA) in relation to its severity. Eighty-one patients with persistent BA, including 21 patients with mild BA, 39 with moderate BA, and 21 with severe BA, were examined. ECG and Holter 24-hour monitoring were performed. Myocardial ischemic episodes were detected in 33% of the patients with moderate BA and in 57% of the patients with severe BA. Silent and painful myocardial ischemia occurred at the equal rate in moderate BA and painful episodes predominated in severe BA. The incidence and degree of supraventricular and ventricular extrasystoles increased with the severity of BA. The paroxysms of ventricular tachycardia, atrial fibrillation and flutter appeared in the presence of BA concurrent with myocardial ischemia.     

Melatonin production in thrombocytes and their functional activity in patients with aspirin asthma

The aim of the investigation was to study melatonin production in thrombocytes and their functional activity in correlation with 6-sulfatoximelatonin (6-SOM) urinary excretion in patients with aspirin-induced bronchial asthma (AIBA). Forty-three patients with bronchial asthma (BA) were examined. The main group consisted of 26 AIBA patients; the comparison group consisted of 17 BA patients with no intolerance to aspirin or other non-steroidal anti-inflammatory drugs; 30 practically healthy individuals constituted the control group. The study found no melatonin production in thrombocytes of AIBA patients: only 13.0 +/- 1.3% of platelets expressed melatonin, while in healthy people 97.7 +/- 0.6% of the cells did. Besides, daytime urinary excretion of 6-SOM, the main melatonin metabolite, was lower in AIBA patients. Lower daytime and higher nighttime melatonin production in AIBA patients correlated with the acceleration of the 1st phase and increased intensity of thrombocyte aggregation, which evidences high thrombocyte reactivity to the inducing agent. The presence of a pathologic reaction of thrombocytes to exogenous melatonin, manifesting by changes in the 1st stage of aggregation, suggests the presence of pathology in thrombocyte membrane-receptor complex and the calcium homeostasis of the cell, which determines constant activation and the participation of thrombocytes in the development of asthmatic syndrome.     

Activity of myocardial sympathetic-adrenal system with various volume of viable myocardium in patients with chronic cardiac failure

AIM: To estimate sympathetic activity in patients with ischemic heart disease (IHD) complicated by chronic cardiac failure (CCF) depending on the volume of viable myocardium measured by dobutamine stress echocardiography (DSE). MATERIAL AND METHODS: Planar myocardial I-231-MIBG scintigraphy and dobutamine stress echocardiography were made in 16 patients (9 males and 7 females) aged 43-75 years with CCF (NYHA class II-III) and ejection fraction under 35%. The ratio maximal MIBG absorption in the left ventricular myocardium to maximal MIBG absorption in the mediastenum (H/M) and lung (H/L) were estimated. RESULTS: By DSE the patients were divided into two groups: responders in whom contractility improved by 4 and more points (9 patients) and non-responders in whom contractility improved by less than 4 scores (7 patients). The groups did not differ by clinical and hemodynamic parameters but group 2 patients had significantly lower H/M and H/L than group 1 patients (1.38 +/- 0.02 and 1.08 +/- 0.06 against 1.61 +/- 0.09 and 1.25 +/- 0.12, respectively, p < 0.05). A direct correlation was found between MIBG absorption (H/M, H/L) and ejection fraction on minimal dobutamine doses (r = 0.77, p < 0.01; r = 0.87, p < 0.001), gain in ejection fraction (r = 0.77, p < 0.01; r = 0.45, p < 0.05), and inverse correlation between MIBG absorption (H/M, H/L) and dyssynergia index on minimal dobutamine doses (r = -0.80, p < 0.001; r = -0.87, p < 0.0001). CONCLUSION: Patients with CCF demonstrate a correlation between sympathetic activity and volume of viable myocardium, inotropic reserve.     

Melatonin effects on functional activity of platelets in patients with bronchial asthma

AIM: To assess effects of epiphysial hormone melatonin in various dose regimens on ADP-induced aggregation of platelets in patients with bronchial asthma (BA). Correlations with urine levels of 6-sulphatoxymelatonin (6-SOMT), basic melatonin metabolite, were made. MATERIALS AND METHODS: Melatonin was given to 17 patients with mild or moderate BA and 16 healthy controls. RESULTS: BA patients were found to have disorders in circadian rhythm of urine 6-SOMT excretion, lack of correlation between platelet functional activity and elevated nocturnal excretion of 6-SOMT, in vitro platelet activation in response to low-dose melatonin and absence of this reaction to high-dose melatonin. CONCLUSION: It is suggested that melatonin may be involved in genesis of bronchoobstructive syndrome in BA.     

Autonomic nervous system examinations

Autonomic nervous system plays a critical role in the regulation of cardiovascular system. We reviewed the autonomic nervous system examinations. Time and frequency domain analyses in heart rate variability is obtained from short- and long-term ECG and have predictive values of prognosis in various conditions of heart disease. Baroreflex testing evaluates autonomic modulation of arterial pressure. Baroreflex sensitivity is expressed by the(arterial blood pressure)/(RR interval in ECG) slope in response to infusion of nitroglycerine or phenylephrine. Decrease in baroreflex sensitivity is superior to heart rate variability in identifying patients with poor prognosis in post myocardial infarction. 123I-metaiodobenzylguanidine (MIBG) is an analogue of norepinephrine and hence cardiac 123I-MIBG imaging can visualize cardiac sympathetic nervous system. Defect area in the early phase(15 to 30 min after injection) indicates localization of ventricular denervation. MIBG uptake, measured as a heart to mediastinum activity ratio, had a high predictive vale for survival. Altered MIBG uptake may also play a significant role in the assessment of arrhythmogenic potential in patients with idiopathic ventricular fibrillation or congenital long QT syndrome.     

Lipid peroxidation and the antioxidant system in patients with bronchial asthma and asthmatic bronchitis subjected to graded physical load

A study was made of lipid peroxidation and the antioxidant system in patients with bronchial asthma (BA) and chronic asthmatic bronchitis (CAB) before and after muscular exercise. Physical exercise in BA patients was accompanied by an increase in the amount of hydroperoxides and a raised activity of superoxide dismutase (SOD) and a drop of peroxidase and catalase activity. Peroxidase and SOD activity did not increase in CAB patients in whom muscular exercise caused no bronchospastic syndrome in the presence of an increase in the amount of hydroperoxides.     

Autonomic nervous system balance, variability and arrhythmia in survivors of myocardial infarction

AIM: To investigate relations between heart rhythm variability (HRV), vegetative balance and electric myocardial activity in myocardial infarction (MI) survivors. MATERIAL AND METHODS: HRV was studied by short 5-min parts of ECG and data of ECG Holter monitoring were analysed for 98 patients who had macrofocal MI 1.5 months to 5 years before. RESULTS: Manifestations of electric heart instability were polymorphic. 69.4% examinees had hyperactivity of the parasympathetic nervous system (PSNS). The influence of the sympathetic nervous system (SNS) increased with growing severity of arrhythmia. Supraventricular arrhythmia occurred more frequently in high PSNS activity, while ventricular arrhythmia occurred more often in SNS prevalence combined with low HRV. CONCLUSION: HRV analysis for MI survivors, especially in combination with Holter ECG monitoring, gives an objective assessment of various manifestations of cardiac dysfunction and therefore enables timely adequate therapy.     

Dispersion of QT interval during holter monitoring in patients with chronic obstructive pulmonary disease and bronchial asthma

The aim of the work was to estimate dispersion of QT interval during Holler monitoring in patients with chronic obstructive pulmonary disease (COPD) and arterial hypertension (AH). The study involved 28 patients with COPD (including 17 with COPD + AH), 31 patients with bronchial asthma (BA) (including16 with BA + AH), and 17 practically healthy subjects. It was shown that a combination of COPD and AH is associated with high-grade ventricular arrhythmia (by Lown-Wolf classification). Dispersion of QT interval indicates that the risk of life-threatening arrhythmia in patients with COPD and AH is unrelated to ventricular extrasystole and ventricular myocardium mass. Patients with BA and AH exhibited electrical instability regardless of myocardial mass only in the presence of ventricular arrhythmia. In the patients with BA and AH the QTcd interval increased in the second half of day, in COPD patients from morning till evening, and in patients with COPD + AH during 24 hours.     

Nuclear medicine imaging for cardiomyopathy

Nuclear medicine techniques have been applied to cardiomyopathy as well as in ischemic heart diseases. Various types of radiopharmaceutical including 201Tl and 99mTc-labeled perfusion tracers, 123I-labeled fatty acid(BMIPP), sympathetic function (MIBG) and tracers for myocardial injuries have been used. Perfusion imaging identifies stress-induced ischemia associated with myocardial damage. Recent application of gated SPECT enables simultaneous assessment of ventricular function. 123I-BMIPP and MIBG can detect metabolic abnormality, which has diagnostic and prognostic value for hypertrophic cardiomyopathy. The MIBG uptake index, heart-to-mediastinum ratio, is known to show good prognostic value for estimating dilated cardiomyopathy. Nuclear medicine plays unique roles for evaluating functional and metabolic derangement in cardiomyopathy.     

Vasoregulating activity of the endothelium and pulmonary hypertension

AIM: To examine vasoregulating endothelial activity in patients with bronchial asthma (BA) with pulmonary hypertension (PH) and free of PH. MATERIAL AND METHODS: A total of 62 BA patients aged between 19 and 52 entered the trial. They were divided into two groups: 44 with PH and 18 free of it. The control group consisted of 35 healthy subjects. Vasoregulating activity of the vascular wall was studied by tests with reactive hyperemia (endothelium-dependent dilation) and 0.05 mg nitroglycerin (endothelium-dependent dilation). RESULTS: It was found that BA patients with PH have a dilated brachial artery, abnormal endothelium-dependent vasodilation of the brachial artery. The artery is low sensitive to shift tension. These changes in functional activity of brachial artery endothelium in BA patients with PH are associated with impaired pulmonary hemodynamics, right ventricular diastolic function.     

Clinical significance of cytological characteristics of bronchial inflammation in obstructive pulmonary diseases

AIM: To evaluate a clinical role of cytological characteristics of induced sputum (IS) and bronchial lavage (BL) in patients with different forms of bronchial asthma (BA) or chronic obstructive bronchitis (COB). MATERIAL AND METHODS: The study included 128 BA patients (53 males and 75 females) at the age of 17 to 70 years (mean age 51.3 +/- 8.4 years) and 53 COB patients (32 males and 21 females) at the age 17 to 70 years. The material for the cytological examination was BL obtained by fibrobronchoscopy and IS obtained after 20-min halotherapy. RESULTS: Percentages of eosinophils, neutrophils, lymphocytes and alveolar macrophages in IS and BL have the same trends and a highly significant correlation coefficient by all the studied cells both in BA and COB patients. CONCLUSION: It was found possible to use IS cytology for evaluation of air way inflammation in BA and COB patients.     

Effect of intramyocardial bone marrow-derived mononuclear cell injection on cardiac sympathetic innervation in patients with chronic myocardial ischemia

Intramyocardial bone marrow cell injection has been associated with improvements in myocardial perfusion and left ventricular function. The current substudy of a randomized, placebo-controlled, double-blinded study, investigated the effect of intramyocardial bone marrow cell injection on myocardial sympathetic innervation in patients with chronic myocardial ischemia. In a total of 16 patients (64 ± 8 years, 13 men), early and late iodine-123 metaiodobenzylguanidine (MIBG) imaging was performed before and 3 months after intramyocardial bone marrow cell injection. No improvements were observed in global early H/M ratio (P = 0.40), late H/M ratio (P = 0.43) and cardiac washout rate (P = 0.98). However, late 123-I MIBG SPECT defect score showed a trend to improvement in the bone marrow cell group (from 31.0 ± 7.1 to 28.1 ± 14.9) as compared to the placebo group (from 33.6 ± 8.5 to 34.5 ± 9.8, P = 0.055 between groups). This trend was mainly driven by a substantial improvement in three bone marrow cell-treated patients, which all had diabetes and severe MIBG defects. In these patients, the extent and severity of MIBG defects improved substantially independent of myocardial perfusion and cell injection sites. The present study does not demonstrate improvements in global cardiac sympathetic nerve innervation after intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. However, regional analysis of sympathetic nerve innervation reveals improvements in three diabetic patients independent of myocardial perfusion, suggestive of a therapeutic effect on diabetic cardiac sympathetic dysinnervation.     

Autonomic mechanisms regulating myocardial contractility in conscious animals

In this review some of the issues and controversies involved in the neural control of the myocardial inotropic response to stress have been discussed. For example, it is surprising that either direct or reflex activation of the sympathetic nerves induces a relatively small increase (20-40%) in the left ventricular inotropic state when compared with the three-five-fold increase associated with maximal dynamic exercise. Studies contrasting the levels of circulating catecholamines with the left ventricular inotropic responses induced by hemorrhage, exercise and exogenously administered catecholamines, suggest that the catecholamine concentration at the synaptic cleft is the primary determinant of the left ventricular inotropic response. Although parasympathetic neural activation alone appears to have little direct influence on the left ventricular inotropic state and central nervous system integration of the autonomic nervous system usually insures there is a reciprocal relationship between sympathetic and parasympathetic neural activity, the potential for parasympathetic inhibition of the response to sympathetic or sympathomimetic augmentation of the intropic response exists. The importance of sympathetic-parasympathetic nervous system interaction in physiologic and pathologic conditions has yet to be defined. It is this type of knowledge of the interactions of reflex pathways which will be critical to the full understanding of autonomic reflex control of myocardial performance under physiologic and pathologic conditions.     

Mast-cell mechanism of the pathogenesis of bronchial asthma and peroxidation of membrane lipids

Examination of 155 patients with atopic, infection-dependent bronchial asthma (BA) and chronic asthmatic bronchitis in the phase of the disease exacerbation and remission has shown that hyperhistaminemia is common not only to atopic but also to infection-dependent BA. It is established that activation of lipid peroxidation of the membranes more pronounced during exacerbation and attacks of asthma is one of the most important alternative mechanisms of mast cell activation, that is supported by the data of experimental morphologic and biochemical studies of the effect exerted by peroxidized fatty acids on histamine liberation and mast cell degranulation.     

Metabolic aspects of the differential diagnosis of chronic asthmatic bronchitis and bronchial asthma

The authors have presented an analysis of the results of a study of patients with chronic asthmatic bronchitis and bronchial asthma to detect possible qualitative differences in changes of indices that characterize the intensity of free radical oxidation and antioxidant activity. With this aim in view the level of lipid peroxidation (LPO), alpha-tocopherol content and SOD activity were determined. In patients with bronchial asthma a raised LPO level was noted in parallel with a decrease in alpha-tocopherol content and SOD activity up to the values below the normal ones. A degree of deviation of the indices from those in health depended on the gravity of a course of bronchial asthma. In patients with asthmatic bronchitis in exacerbation and remission with a raised LPO level alpha-tocopherol content and SOD activity remained within normal. These differences can be used for differential diagnosis.