Ex Vivo Analysis of an Association of Mechanical Strength of Dilated Ascending Aorta with Tissue Matrix Metalloproteinases and Cytokines.

We analyzed the associations of the mechanical strength of dilated ascending aorta wall (intraoperative samples from 30 patients with non-syndromic aneurysms) with tissue MMPs and the cytokine system. Some samples were stretched to break on an Instron 3343 testing machine and the tensile strength was calculated; others were homogenized and the concentrations of MMP-1, MMP-2, MMP-7, their inhibitors (TIMP-1 and TIMP-2), and pro- and anti-inflammatory cytokines were determined by ELISA. Direct correlations between aortic tensile strength and concentrations of IL-10 (r=0.46), TNFα (r=0.60), and vessel diameter (r=0.67) and an inverse correlation with patient's age (r=-0.59) were revealed. Compensatory mechanisms supporting the strength of the ascending aortic aneurysm are possible. No associations of MMP-1, MMP-7, TIMP-1, and TIMP-2 with tensile strength and aortic diameter were found.

Subacute myocardial infarction detected by technetium-99m-labeled somatostatin analog scintigraphy.

Recently, the applicability of somatostatin receptor-targeted (SSTR-t) radiotracers for post-ischemic myocardial inflammation imaging has been shown using PET. Currently, there are no studies which demonstrate ability of SPECT and technetium-99m SSTR-t radiotracers to detect inflammation, which appears in response to acute myocardial infarction (AMI). A case of 51-year-old male with acute anterior myocardial infarction (AMI) with ST elevation has been presented. This patient on 7th day after AMI onset underwent SPECT/CT (by cardiac cadmium-zinc-telluride gamma-camera) with 99mTc-Tectrotide, cardiac MRI with gadolinium and, on 9th day after AMI, myocardial perfusion scintigraphy (MPS) at rest. Clear myocardial uptake of 99mTc-Tectrotide, predominantly in apical and intermediate anterior wall of left ventricle was detected. The uptake matched with areas of hypoperfusion (by SPECT) and myocardial injury (by MRI). This case demonstrated the applicability of technetium-99m-labeled SSTR-t radiotracers for post-infarction inflammation imaging. Currently assumed, that SSTR-t radiotracers reflect an increased number of activated macrophages infiltrating infarcted myocardium, which is not possible using any other imaging technique. Thus, potentially, SSTR scintigraphy may be useful for diagnosis and monitoring of myocardial post-infarction inflammation as well as for anti-inflammatory image-guide therapy assessment.

Cardiac 123I-mIBG scintigraphy for prediction of catheter ablation outcome in patients with atrial fibrillation.

BACKGROUND: Previous studies show inconsistent results on the role of innervation imaging (with 123I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post-CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF. METHODS: 123I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patient was followed for 12 months. RESULTS: Multivariable analysis demonstrated that late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/Mlate <1.6 (sensitivity 73.53%, specificity 81.3%, AUC 0.792, P < .001) and WR > 25.11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0.712, P < .001) indicate high probability of AF relapses during 12 months after CA. CONCLUSION: Pre-CA parameters of global cardiac sympathetic activity estimated by 123I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients with normal LVEF and absence of significant CAD.

[Role of imaging modalities in the choice of treatment strategy for mega aorta syndrome]. / Rol' luchevykh metodov diagnostiki v vybore taktiki lecheniya sindroma megaaorty.

The authors report a 76-year-old female with mega-aorta syndrome that was asymptomatic for a long time. The first symptoms appeared after ascending aorta enlargement up to 81 mm and compression of superior vena cava. The patient underwent frozen elephant trunk procedure. The authors demonstrate the possibilities of assessing the aortic strain by ECG-synchronized CT angiography and 2D transesophageal ultrasound with speckle tracking. Potential role of these methods in determining the type of aortic reconstruction is discussed.

Experimental Study of a Radiopharmaceutical Agent Based on Modified Fatty Acid Labeled with Technetium-99m.

Using rat model of coronary occlusion, we studied pharmacokinetics and the efficiency of a new radiopharmaceutical agent 99mTc-PDA-DTPA intended for diagnostics of changes in myocardial metabolism and its analogue 123I-PMPDA. 99mTc-PDA-DTPA was eliminated mostly by the kidneys and maximal concentration in the heart was attained within 60 min after intravenous injection; no accumulation in the area of myocardial infarction was observed. The studied substance was inferior to its analogue 123I-PMPDA by the quality of scintigraphic visualization of the heart.

Analysis of mechanisms of interaction between ciprofloxacin-based radiopharmaceutical labeled with technetium-99m and cultured Staphylococcus aureus.

Mechanisms of interaction between ciprofloxacin-based radiopharmaceutical labeled with technetium-99m and cultured Staphylococcus aureus were studied. The substance, reagent for radiopharmaceutical, and the radiopharmaceutical demonstrated similar bactericidal activity against the test bacterial cultures, which confirmed specific antibacterial activity of technetium-99m-labeled ciprofloxacin. The technetium-99m-labeled antibiotic reversibly interacts with inactivated Staphylococcus aureus culture, which indicates the existence of an additional non-specific pathway for radiopharmaceutical accumulation in the bacterial inflammation focus. Our experiment ruled out the possibility of binding free technetium-99m at concentrations <5% (its concentration in the radiopharmaceutical) with Staphylococcus aureus.

[Capabilities of 99mTc-pyrphotech single-photon emission computed tomography in combination with myocardial perfusion scintigraphy in the evaluation of inflammatory changes in the heart of patients with persistent atrial fibrillation].

AIM: To estimate the capabilities of 99mTc-pyrphotech single-photon emission computed tomography (SPECT) in the diagnosis of myocardial inflammatory changes in patients with persistent atrial fibrillation (AF). SUBJECTS AND METHODS: Nineteen patients (11 males and 8 females, mean age 47.46 ± 9.92 years) with persistent idiopathic AF underwent preoperative complete clinical and instrumental examination. 99mTc-pyrphotech SPECT was performed to identify foci of myocardial inflammatory changes. After completing 99mTC-pyrphotech scanning, resting myocardial perfusion scintigraphy with 99mTC-methoxyisobutylisonitrile (99mTc-MIBI) was performed in accordance with the standard protocol. The scintigrams obtained in both studies were then combined using the applied programs Jet Stream Workspace Release 2.5 (Philips) and the application Fusion. During invasive intervention, endomyocardial samples were intraoperatively taken from all the patients for histological and immunohistochemical examinations. RESULTS: Abnormal 99mTc-pyrphotech myocardial accumulation was found in 7 (36.8%) of the examinees, multiple foci in 3 cases and single foci in 4. Analysis of perfusion scintigrams indicated that the mean abnormal accumulation of 99mTc-MIBI in the left ventricle was 3.75 ± 0.88% (maximum 9%). Histological examination of endomyocardial samples from 19 patients with persistent AF verified myocarditis in 4 (21%) patients and myocardial sclerosis concurrent with other abnormalities in 15 (78.9%) patients. CONCLUSION: Latent lymphocytic or polymorphic cellular myocarditis of viral etiology is a cause of idiopathic AF in 20% of the cases. 99mTc-pyrphotech scintigraphy may be one of the primary noninvasive diagnostic techniques for the detection of myocardial inflammation in this form of arrhythmia.

Radiomic Phenotype of Periatrial Adipose Tissue in the Prognosis of Late Postablation Recurrence of Idiopathic Atrial Fibrillation.

The aim of the study is to find new predictors of postablation atrial fibrillation (AF) recurrence in patients with lone AF using a texture analysis of the periatrial adipose tissue (PAAT) of the left atrium. Materials and Methods: Forty-three patients admitted for lone AF catheter ablation, who had undergone multispiral coronary angiography, were enrolled in the study. PAAT segmentation was performed using 3D Slicer application followed by extraction of 93 radiomic features. At the end of the follow-up period, patients were divided into 2 groups depending on the presence or absence of AF recurrence. Results: 12 months of follow-up after catheter ablation, postablation AF recurrence was reported in 19 out of 43 patients. Of 93 extracted radiomic features of PAAT, statistically significant differences were observed for 3 features of the Gray Level Size Zone matrix. At the same time, only one radiomic feature of PAAT, Size Zone Non Uniformity Normalized, was an independent predictor of postablative recurrence of AF after catheter ablation and 12 months of follow-up (McFadden's R2=0.451, OR - 0.506, 95% CI: 0.331‒0.776, p<0.001). Conclusion: The radiomic analysis of periatrial adipose tissue may be considered as a promising non-invasive method for predicting adverse outcomes of the catheter treatment, which opens the possibilities for planning and correction of patient management tactics after intervention.

[Radionuclide methods for diagnostics of non-rheumatic myocarditis and postmyocarditic cardiosclerosis].

We compared the results of comprehensive scintigraphic examination of 35 patients with suspected myocarditis and the data of clinical, immunological, laboratory and instrumental studies. The patients were divided into 3 groups. Group 1 included 11 patients with preliminary diagnosis of acute myocarditis, group 2--11 patients with chronic myocarditis, group 3--13 patients with postmyocarditic cardiosclerosis. All patients were tested for antimyocardial antibodies, underwent 99mTc-HMPAO-labeled leukocyte and perfusion scintiography of myocardium. The study did not reveal significant differences between the three groups as regards the results of laboratory and instrumental studies. Elevated titers of antimyocardial antibodies were found in 70% of the patients in group 1, 100% in group 2, and 46% in group 3. Patients with chronic myocarditis had the highest titers of antibodies. Pathological accumulation of 99mTc-HMPAO-labeled leukocytes in myocardium was documented in 36.4 and 81.8% of the patients of groups 1 and 2 respectively. They were absent in the heart of group 3 patients. Disturbed myocardial perfusion was recorded in 45.5, 81.8 and 84.6% in groups 1, 2 and 3 respectively. The magnitude of accumulation of leukocytes was not significantly different between the groups. Results of the study suggest rather high specificity of radionuclide techniques for diagnostics of inflammatory lesions in myocardium. However, further studies are needed to confirm their sensitivity and accuracy.

Scintigraphic Imaging of Inflammation in the Aortic Wall Using 99mTc-Pyrophosphate.

The aim of this study was to develop and test a technique for scintigraphic examination of the thoracic aorta, which allows for visualizing foci of inflammation. Materials and Methods: The study included 15 patients (median age - 61 [47; 73] years) with aortic dilatation more than 45 mm and thoracic aortic aneurysm who were candidates for surgical treatment. All patients underwent a chest scintigraphy with 99mTc-pyrophosphate 48 h before surgery to identify foci of inflammation in the aortic wall. The new technique included intravenous administration of 370 MBq of a radiopharmaceutical (RP), registration of scintigrams at 3 and 6 h after injection of RP in a tomographic mode combined with X-ray computed tomography. After the image reconstruction, subtraction of the later scintigrams from the early ones was performed, followed by analysis of the final images. The results of scintigraphy were compared with the histological data obtained from intraoperative samples of resected aorta. Results: According to the results of this novel scintigraphic technique, artifacts from the radioactivity of the vascular blood pool were eliminated and pathological RP uptake was identified in 5 (33.3±1.5%) out of 15 examined patients. The "focus/vessel lumen" ratio averaged at 1.47 [1.30; 1.48]. Histological examination of resected aorta samples confirmed the presence of chronic inflammation in 4 (26.7±1.3%) out of 15 patients. Parameters of diagnostic efficiency were: sensitivity - 100%, specificity - 91%, diagnostic accuracy - 93%. Conclusion: The method of scintigraphic diagnostics of inflammatory processes in the aorta using 99mTc-pyrophosphate, supplemented by subtraction of the late from the early images, makes it possible to eliminate artifacts from the radioactivity of the aortic blood pool and to reveal the pathological RP accumulation indicating the areas of inflammation in the aortic wall.

[Clinical experience of the use of autologous mononuclear bone marrow cells in patients with ischemic heart disease and dilated cardiomyopathy].

Between March 2003 and February 2005 cell therapy with mononuclear bone marrow cells (MBMC) was used in 38 and 4 patients with ischemic heart disease and dilated cardiomyopathy, respectively. Intracardiac administration of MBMC (87+/-12 millions) was carried out during coronary artery bypass surgery and/or left ventricular aneurysm resection (n=25) or in cardiac catheterization laboratory (n=17). For verification of cells fixation they were labeled with "Ceretec" 99mTc-HMPAO. Accumulation of labeled cells after 24 hours was 1.6+/-0.001%. After 6 months parameters of intracardiac hemodynamics and transitory myocardial perfusion defects improved significantly in all patients with ischemic heart disease.

[Using cytokines to stimulate neoangiogenesis and cardiac regeneration].

Data published on the use of cytokines for the stimulation of neoangiogenesis and cardiac regeneration have been systematized. There is evidence that insulin-like growth factor (IGF1) can stimulate proliferation of cardiomyocytes; hepatocyte growth factor (HGF) does not influence the mitosis of cardiac cells, but prevents post-infarction remodeling of heart; vascular endothelial growth factor (VEGF) stimulates proliferation of endothelial cells in vitro and neovasculogenesis in the ischemic heart in vivo for both animals and humans; fibroblast growth factor (FGF) can also induce neovasculogenesis in the ischemic heart; granulocyte-colony-stimulating factor (G-CSF) can mobilize stem cells and endothelial progenitor cells in bone marrow, which are involved in neoangiogenesis and cardiac regeneration; erythropoietin can mobilize endothelial progenitor cells from bone marrow and induce neovascularization of ischemic tissue in vivo. It is suggested that VEGF, G-CSF and erythropoietin are the most promising compounds for the stimulation of neoangiogenesis and cardiac regeneration in patients with myocardial infarction.

[Cardiomyoplasty with autological mononuclear cells of the bone marrow in patients with acute myocardial infarction].

AIM: To study efficacy and safety of transplantation of bone marrow autologous mononuclear cells (BMAMC) in patients with acute myocardial infarction; to examine BMAMC distribution in the human body after intracoronary introduction. MATERIAL AND METHODS: The open controlled trial investigated 26 AMI patients (16 entered the study group and 10 were controls). Cell cardiomyoplasty with BMAMC was performed by intracoronary injection of the cells after stenting the coronary artery supplying blood to the infarction zone on AMI day 7-21. BMAMC were isolated by gradient centrifugation. Distribution of mononuclear cells was studied with radionuclear indication of the cells 99m-Tc-HMPAO. All the patients were examined with Tl-199 perfusion scintigraphy of the heart 2 weeks and 6 months after the treatment, echocardiography, 24-h ECG monitoring, 6-min walk test. RESULTS: All the patients were followed up for 6 months. Two patients (one in each group) developed recurrent myocardial infarction 3 months after the first. Radionuclide investigations revealed fixation of labelled mononuclear cells in the heart both in initial hours after the treatment and 24 hours after it. As shown by myocardial scintigraphy, intracoronary administration of the cells with short-term arterial occlusion was followed by much greater number of labeled cells. By follow-up month 6, in the study group, left ventricular ejection fraction increased more: 12.7 +/- 3.2% versus 10.4 +/- 2.5% in the control group (p = 0.09); moreover, a stable defect of myocardial perfusion reduced more (by 29 +/- 24% against 20 +/- 18%, respectively, p = 0.1). Malignant arrhythmia, complications during and after bone marrow aspiration, intracoronary administration of cell suspension were not registered. CONCLUSION: Intracoronary administration of BMAMC in AMI patients is safe and provides their transfer and fixation in the myocardium. BMAMC transplantation has a positive effect on recovery of perfusion and contractile function of left ventricular myocardium in AMI patients.

[Determination of the efficiency of single-photon emission computed tomography with 99mTc-HMPAO-labelled leukocytes in the diagnosis of myocarditis: Comparison of scintigraphic and histological data].

OBJECTIVE: to determine the efficiency of single-photon emission computed tomography (SPECT) with 99mTc-HMPAO- labelled leukocytes in diagnosing myocarditis, by comparing scintigraphic and histological data. MATERIAL AND METHODS: The investigation enrolled 35 patients with suspected myocarditis, who were planned to undergo coronaroventriculography or intervention with endomyocardial biopsy. Prior to endomyocardial biopsy, all the patients underwent myocardial scintigraphy using 99mTC-exametazime-labelled leukocytes. The results of myocardial scintigraphic and histological examinations were compared. RESULTS: Abnormal myocardial 99mTc-HMPAO-labelled leukocyte accumulation was detected in 7 (20%) examinees. Myocarditis was histologically verified in 9 (25.7%) persons. Our findings showed that the sensitivity of 99mTc-HMPAO-labelled leukocyte SPECT in diagnosing myocardial inflammatory changes was 62%; its specificity and diagnostic accuracy were 92% and 85%, respectively. Conclusion. 99mTc- HMPAO-labelled leukocyte scintigraphy is today one of a few procedures for the primary noninvasive diagnosis of myocardial inflammation. However, in view of its sufficiently low sensitivity and laboriousness and the sigh cost of consumables, the technique is irrationally used in routine clinical practice.

[Regeneration of myocardium]. / Regeneratsiia miokarda.

It has been systematized modern data on the myocardial regeneration and the regulation of cardiac cell proliferation in mammals and man. It has been performed an analysis published works which indicate that cardiomyocyte division and DNA synthesis in myocardial cells increase in many times during different pathological conditions. It has been generalized and analyzed results of experimental and clinical researches on the participation of stem cells in the regeneration of the heart. It has been present literature data on the telomeres and telomerase in cardiomyocytes.

Comparative scintigraphic study of 99mTc ciprofloxacin pharmacokinetics after intravenous and lymphotropic administration in experimental pulmonary suppuration.

Intravenously injected 99mTc ciprofloxacin is rapidly accumulated and washed from the septic focus. Lymphotropic injections provide targeted and long-lasting effect of the antibiotic. After injection into the interspinous ligament the drug slowly enters the inflammation area (by-passing the urinary organs and liver), where it is maximally accumulated only after 24 h, which allows to reduce the number of injections and the total dose of the antibiotic.