Ultrasound inflammation imaging in rats with myocardial ischemia-reperfusion: Evaluation by non-specific targeted contrast microbubbles

Background: Reports on ultrasound inflammation imaging with non-specific targeted microbubbles in the heart have been scarce. We investigated whether inflammation induced by myocardial ischemia-reperfusion in rats could be evaluated by ultrasound inflammation imaging with non-specific targeted microbubbles. Methods: Six rats subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by 4 h of reperfusion (ischemia group) and 4 rats subjected to the sham operation (sham group) were used. Ultrasound inflammation imaging was performed 4 h after reperfusion, and non-circulating signal intensity (SI), which reflects the signal derived from microbubbles phagocytosed by neutrophils in inflamed tissue, was calculated by the SI difference between the initial and subsequent imaging both in the LAD and non-LAD areas. The accumulation of neutrophils was confirmed by myeloperoxidase (MPO) staining. Results: Non-circulating SI in the LAD area was significantly greater for the ischemia group than the sham group [5.19 ± 2.19 (ischemia) vs. 0.31 ± 0.13 (sham) dB, p < 0.01]. Non-circulating SI in the LAD area was significantly higher than that in the non-LAD area when compared in the same rat of the ischemia group [5.19 ± 2.19 (LAD) vs. 0.18 ± 0.64 (non-LAD) dB, p < 0.01]. MPO-positive cells were confirmed in the LAD area of the ischemia group. Conclusion: Inflammation induced by myocardial ischemia-reperfusion in rats could be quantitatively assessed by ultrasound inflammation imaging with non-specific targeted microbubbles.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12574-010-0051-z

A case of cardiac sarcoidosis masquerading as arrhythmogenic right ventricular cardiomyopathy awaiting heart transplant

SummaryWe report a case of 45-year-old man, who was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) and presented with right ventricular (RV) enlargement with a global decrease in RV contractility accompanied by impairment of left ventricular function. He was placed on the heart transplant waiting list. Endomyocardial biopsy from RV septal wall did not show any evidence of sarcoidosis or inflammatory change. Four years after he was put on the heart transplant waiting list, a computed tomography chest scan for the purpose of anatomical evaluation for coronary sinus prior to biventricular pacing lead implantation incidentally showed bilateral hilar lymphadenopathy, which suggested the possibility of sarcoidosis. Biopsy of the inguinal lymph node pathologically was consistent with sarcoidosis. The 2[18F]fluoro-2-deoxy-d-glucose positron emission tomography scanning (FDG-PET) demonstrated intense uptake in the myocardium, and the patient was finally diagnosed as having cardiac sarcoidosis. After steroid treatment, the abnormal FDG-PET uptake disappeared. The patient therefore represented a case of cardiac sarcoidosis masquerading as ARVC. It should be recognized that RV involvement is one of the manifestations in cardiac sarcoidosis

Expression and function of ephrin-B1 and its cognate receptor EphB2 in human abdominal aortic aneurysm

We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al

Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid

The predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA

Expression and function of ephrin-B1 and its cognate receptor EphB2 in human abdominal aortic aneurysm

We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al

Myocardial Impairment Detected by Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy: Comparison with 99mTc-MIBI/Tetrofosmin and 123I-BMIPP SPECT

Purpose: Myocardial fibrosis is considered to be an important factor in myocardial dysfunction and sudden cardiac death in hypertrophic cardiomyopathy (HCM). The purpose of this study was to compare myocardial fibrosis detected by late gadolinium enhancement (LGE) on cardiac MRI with myocardial perfusion and fatty acid metabolism assessed by single photon emission computed tomography in HCM.Materials and Methods: We retrospectively evaluated 20 consecutive HCM patients (female, 7; mean age, 53.4 years) who underwent LGE, technetium-99m methoxyisobutylisonitrile/tetrofosmin (99mTc-MIBI/tetrofosmin), and iodine-123 beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging. We calculated the myocardium-to-lumen signal ratio (M/L) for LGE in 17 segments based on the American Heart Association statement. Scoring of 99mTc-MIBI/tetrofosmin (PI) and 123I-BMIPP (BM) was performed for each segment using a 5-point scale (0, normal; 4, highly decreased).Results: Nineteen of 20 patients (95%) and 153 of 340 segments (45%) showed LGE. M/Ls were 0.42ｱ・.16, 0.55ｱ・.17, and 0.65ｱ・.24 in PI0/BM0, PI0/BM1-4 and PI1-4/BM1-4, respectively. All M/Ls were significantly higher than that of a normal control (0.34ｱ・.14) (p<0.001).Conclusions: Myocardial fibrosis in HCM can occur despite normal perfusion and fatty acid metabolism, and is more strongly associated with disorders of fatty acid metabolism than with perfusion abnormalities. M/L may be a useful indicator of disease severity

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV